Understanding Depression: A Complete Guide To Its Diagnosis and Treatment

Understanding Depression:
A Complete Guide to Its

Diagnosis and Treatment
Donald F. Klein, M.D.

Paul H. Wender, M.D.
OXFORD UNIVERSITY PRESS

Contents
1. Introduction, 1
2. Symptoms of Mood Disorders: Recognizing Biological

Depression, 9
The Question of Names, 9
Recurrent Problems in Patients’ Illnesses, 14
Treatment, 46
Mild Forms of Depression and Manic-Depression
(Bipolar Disorder), 59
The Interpersonal Consequences of Depression and
Manic-Depression, 67
3. What Happens to the Depressive or Manic-Depressive

Individual Over Time?, 69
The Symptoms of Depression in Children and
Adolescents, 71
The “Natural History” of Depression and Manic-Depression, 74
xi
1
Introduction
DEPRESSION MAY be a normal human emotion—a

response to loss, disappointment, or failure. Some depressions,
however, should more properly be put in the category of com-
mon biological diseases, destructive to families, to careers, to re-
lationships. Depression can be lethal. It has been estimated that
perhaps somewhere between 10 and 30 percent of depressives
and manic-depressives kill themselves. But the figure may actu-
ally be lower; obtaining exact figures is extremely difficult. What
is known is that since the widespread use of the “selective sero-
tonin reuptake inhibitors” (SSRIs) such as Prozac, suicide rates
have declined substantially in a number of countries.
If you have picked up this book and are reading this sen-
tence, there is a good chance that you are worried about de-
pression in yourself or others in your family. Most serious
depression requires medical treatment even through it may be
triggered or worsened by psychological factors. Correct medi-
cal diagnosis should lead to a treatment that in most instances
is effective, moderately fast, and inexpensive.
The aims of this book are:
1. To explain what biological depression is and to clarify the

difference between depression, a normal emotion, and bio-
logical depression, and illness.
1
2 Introduction
2. To give the reader brief self-screening tests that can help to

determine if he or she (or a relative or friend) requires fur-
ther evaluation.
3. To describe other psychiatric disorders that are associated
with biological depression, such as manic-depression and
panic attacks.
4. To indicate how someone suffering from biological depres-
sion can find help.
5. To provide a family guide to the treatment of biological de-
pression and related disorders.
6. To discuss in some detail the treatment of depression.
7. To discuss problems in the development of new treatments
and improving medical care.
Let us elaborate on these points:
1. Biological depression is common—in fact, depression and

manic-depression are among the most common physical disor-
ders seen in psychiatry. One woman in five and one man in ten
can expect to develop a depression or manic-depression some-
time during the course of their lives. In other words, one person
in seven can expect to develop depression or manic-depression
during his or her lifetime—in total, well over 30 million of the
current United States population.
Untreated depressive illness can lead to personal, familial,
and social disasters. A particularly vivid statement of what it
means to be severely depressed comes from Russell Hampton’s
autobiography, The Far Side of Despair (1975):
If there were a physical disease that manifested itself in

some particularly ugly way, such as pustulating sores or
a sloughing off of the flesh accompanied by pain of an
intense and chronic nature, readily visible to everyone,
and if that disease affected fifteen million people in our
country, and further, if there were virtually no help or
succor for most of these persons, and they were forced to
walk among us in their obvious agony, we would rise up
as one social body in sympathy and anger. We would give
of our resources, both human and economic, and we
Introduction 3
would plead and demand that this suffering be eased.

There isn’t such a physical disease, but there is such a dis-
ease of the mind, and about fifteen million people around
us are suffering from it. But we have not risen in anger
and sympathy, although they are walking among us in
their pain and anguish.
Depressive illness is common, painful, and dangerous, but

since Russell Hampton wrote that passage, new effective treat-
ments for depression have been developed that yield excellent
results, and we will discuss these in a moment. Yet, in spite of
our progress, the number of people in the United States cur-
rently suffering from this disease is probably twice the number
stated by Hampton.
With regard to the lethality of depression, suicide is the eighth
leading cause of death in adults (often through apparent acci-
dents) and is the second leading cause of death in children and
adolescents. The ability to recognize depressive illness in your-
self or loved ones may be a matter of life and death.
2. Our second aim, to provide a self-screening test for de-
pression, is directed at the widespread inability to recognize
depression (and therefore the failure to secure proper treatment
for it).
3. Our third goal is to help the reader recognize conditions
related to depression—such as mania (one phase of manic-
depression) and a milder depressive disorder called dysthymia.
The tests we provide for depression and the other conditions
are like those used by psychiatrists in diagnosing these illnesses.
For some related disorders, such as panic attacks, we are not
providing a self-screening test but believe that our description
is clear enough for easy recognition.
The purpose of these self-screening tests is not to enable you
to make a diagnosis. Rather, the purpose is to help you to know
when to seek expert help. People can be taught to recognize
the warning symptoms of depressive illness (and panic attacks),
just as they have been taught to detect the warning symptoms
of cancer. The purpose of the American Cancer Society’s “seven
warning signs of cancer” is not to enable people to diagnose
4 Introduction
themselves but to teach them to watch for suggestive symptoms—

for example, to examine the breast for lumps and to be alert for
sores that do not heal or moles that change color. Learning to
observe such bodily changes contributed to a medical early
warning system.
The prospective patient is in a better position to find possible
early signs of cancer than the doctor is. Usually such symp-
toms are not signs of cancer. But if they are, they will have been
detected early—and the cancer will be more likely to respond
to treatment. In the same way, we want people who read this
book to be able to recognize the early symptoms of depression.
We want to teach them a psychiatric early warning system so
that they can get treatment for themselves or someone close to
them before the danger has mounted.
People know when they are sad, of course, and understand-
ably do not think of that feeling—and the related feeling called
depression—as an illness. Depressive illness can be insidious
because it frequently resembles the kind of unhappiness that is
a normal part of human living. Without help, most people can-
not distinguish between psychological depression and biologi-
cal depressive illness. One reason is that most people, when
depressed, immediately trace their emotional state to problems
in their current or past life, failing to recognize distinctive clues
hinting that they may instead be suffering from a disease. An-
other reason is that biological depression can be triggered by
life events, which may lead people to discount depressive dis-
ease as simply normal psychological responses.
4. It is essential that people who suspect they are suffering
from depression know who is qualified to help. Not all physi-
cians or mental health workers—such as psychologists, social
workers, and psychiatric nurses—have had adequate training
in the diagnosis and treatment of depression. Since 1980 the
American Psychiatric Association has published a diagnostic
manual that defines the various mental disorders in concrete
language that is easy to understand. However, simply reading
descriptions of diagnoses does not provide sufficient training.
The student must also have years of expertly supervised expe-
rience in order to apply these definitions in a reliable way. The
Introduction 5
availability of the diagnostic manual has stimulated the teach-

ing of diagnosis across the range of mental health workers, but
the best treatment of depression requires further specialization.
However, while some of these other mental health workers have
learned to diagnose depression, many have not and may fail to
recognize these disorders. And, more important, some may treat
depressive and manic-depressive patients only with counsel-
ing or psychotherapy, preventing them from getting appropri-
ate treatment with medication.
Another problem is that nonmedical therapists cannot pro-
vide complete treatment of depression because the optimum
treatment often involves the use of medication; only physicians
can prescribe antidepressant medication. Those who cannot
prescribe antidepressant medication sometimes tend to down-
play its importance. Even some psychiatrists, however, do not
have sufficient training to diagnose or treat biological depres-
sion correctly because the field is relatively new and rapidly
growing.
Because biological depression is frequently chronic, it may
require long-term continuing treatment, like any other chronic
biological illness. This treatment is best administered by psy-
chiatrists who specialize in biological psychiatry. There is a vast
difference in the training of psychiatrists and that of family
physicians or internists. The psychiatrists spend three years
studying the treatment of psychiatric disease, including a sub-
stantial period learning the best techniques for administering
medication. It is essential that people who suspect they are suf-
fering from depression know whom to approach for help. It is
extremely important to consult a qualified physician, usually a
biological psychiatrist, in order to secure both accurate diagno-
sis and correct treatment.
The family practitioner may have only six months of training
in psychiatry, and the internist usually has less. Though such
physicians may have acquired much “clinical experience,” their
training has usually been on-the-job. Some physicians have taken
special courses and expanded their clinical experience with a
view to becoming expert in the treatment of depression. How-
ever, these doctors are in the minority. An extremely important
6 Introduction
development for the health of the public would be a move to-

ward helping family practitioners to recognize the importance
of depression and to include an examination for depression in
their standard patient evaluation. Nevertheless, in the treatment
of mental illness as in the rest of medicine, the specialist—the
biological psychiatrist—is likely to be more familiar with ad-
vanced techniques. If one needs to have his thyroid gland re-
moved, one wants to be operated on by a thyroid specialist, not
by a general surgeon, whose experience is in a variety of areas
and who has performed fewer such operations than the thy-
roid specialist.
Since both psychiatrists and family physicians may not have
an adequate background to diagnose and treat biological de-
pression, the patient must take an active, often uncomfortable
role by asking the physician if he or she has had a special inter-
est or training in depression and is widely experienced in the
use of medication for this disease. It is also helpful to ask about
the physician’s attitude toward psychotherapy. If he indicated
that psychotherapy is the core of the treatment and that medi-
cation is only a minor adjunct to be used as little as possible, he
is not up-to-date.
On the other hand, the role of the psychiatrist has not been
reduced to writing prescriptions. He must take the time to get
to know the patient by systematic detailed inquiry and medi-
cal examinations. Furthermore, he must take the time to an-
swer all the patient’s questions about outcome, symptoms, side
effects, course, relapse, prognosis, heredity, etc.—or he is not
providing adequate care.
5. The most effective treatment requires that the patient and his
or her family be active participants. The family’s understanding
of the patient’s illness and the family’s relationship to the pa-
tient can support or undercut medical treatment and can psy-
chologically amplify or diminish symptoms. The family’s roles
are multiple, including “caring,” monitoring the patient’s symp-
toms, and helping the physician assess the patient’s response
to treatment. The views of depressives and manic-depressives
of their world are altered by the distorting lenses of their ill-
ness. The family can help immensely by providing an objective
view of the patient’s functioning.
Introduction 7
In urging family participation, we are not referring to

“codependency”—a current faddish term in psychiatry and
clinical psychology. This word refers to the (usually undocu-
mented) notion that the patient’s illness is supported, encour-
aged, or amplified by other family members. “Codependency”
is misleading as well as faddish. Since biological depression is
a disease, it can neither be caused nor cured by changes in the
way the family related to the patient. The family’s actions can
worsen or lessen the patient’s symptoms, but only to a limited
extent. The family has a major impact upon helping the patient
get appropriate care; if the family is misguided, it can prevent
the patient from receiving such care by belittling or denying
the seriousness of the illness.
6. We want next to discuss the treatment of depression. The
evidence is compelling that effective medical treatment can re-
lieve or totally remove the symptoms in over 80 percent of
people with severe depression. The antidepressant medications
are not habit-forming or abusable. Research studies have shown
that the administration of antidepressants in normal people
produces certain side effects but no “high” feelings or eupho-
ria. In the more than 40 years that they have been available,
they have never been sold on the “street” as illegal drugs. There
has been much misguided and sensational discussion of anti-
depressant drugs in the popular press.
In urging treatment of depressive disease by medication, we
are not ignoring the possible usefulness of psychotherapy. How-
ever, we believe that the prescription of antidepressant medi-
cation should almost always be the first step in the treatment
of biological depression. Following relief of symptoms through
the use of medication, psychotherapy may be able to alleviate
many of the residual psychological symptoms.
This book will deal only briefly with theoretical issues that
are of interest to people studying depression. We will say some-
thing about brain chemistry and its relationship to mood, but for
the most part we will direct our attention to practical issues.
One last point—the most important point. This is not another
self-help book. Our overriding message is that certain forms
of depression cannot be overcome by self-help. They require
8 Introduction
medical evaluation and medical treatment. The purpose of this

book is to assist people to recognize when they need profes-
sional help, to indicate how they can get that help, and to clarify
how they can best work with the health provider in the treat-
ment of the disease of biological depression. We also hope to
inform our readers of problems improving their treatment.
2
Symptoms of
Mood Disorders:
Recognizing Biological
Depression
The Question of Names
THE NAMES of the “mood disorders” have changed

repeatedly, and the layperson is generally confused about their
meaning. The mood disorders we will discuss are: depression
or unipolar depression, manic-depression or bipolar disorder,
dysthymic disorder, and cyclothymic disorder. There are two
major types of depression. In the first, depression or unipolar
depression, the patient’s mood varies between being either
normal or depressed; he or she never becomes excessively
elated. In the second, manic-depression or bipolar illness, the
patient’s mood varies between being depressed (as in unipolar
depression) and being “high” or “euphoric.” In the past manic-
depression was sometimes called manic-depressive psychosis. Psy-
chosis is another word for “insanity,” including symptoms such
9
10 Understanding Depression
as delusions (false beliefs) and hallucinations. We now realize

that most people with manic-depression are never psychotic.
Dysthymia refers to a state of mild chronic depression. Cy-
clothymia refers to a condition in which the person’s moods
swing up and down for days, weeks, or months at a time, with
symptoms that are not as severe as those in manic-depression.
There is also much confusion about whether these illnesses
are produced by psychological experiences or by malfunction-
ing within the brain (a “chemical imbalance”). The major point
we wish to make is that depression, manic-depression, dysthy-
mic disorder, and cyclothymic disorder are diseases, the prod-
uct of abnormal biological functioning. We will use the terms
biological depression, clinical depression, and depressive ill-
ness interchangeably.
With depressive illness, as with any other disease, the physician—
the psychiatrist—has guidelines and rules for making the di-
agnosis. The rules used for diagnosing depressive illness are
simple. They depend on the presence or absence of symptoms
that anyone can recognize. The layperson can use these rules
to rate himself and come to a rough conclusion:
I probably do have a depressive illness.
I might have a depressive illness.
I don’t have a depressive illness.
The words “might” and “probably” are used because deter-
mining how severe a symptom is—or isn’t—is a “judgment
call.” The skilled psychiatrist’s expertise involves the ability to
judge the seriousness of a person’s symptoms. This judgment
is based on experience with many patients and includes the
ability to judge not only what a person says but how he says it.
The psychiatrist uses a systematic interview to evaluate what a
depressed person tells him. This can be used to fill out a com-
prehensive rating scale and is more accurate than giving people
questionnaires.
Here we present the psychiatrist’s rating scale in the form of
questions that someone might be asked during an evaluation
interview. After using the rating scale, we go on to the fuller
description of the symptoms and brief histories describing how
these symptoms have appeared—or have been hidden—in pa-
Symptoms of Mood Disorders 11
tients we have treated. In elaborating on the description of de-

pression we include symptoms that are not part of our initial
self-rating questionnaire but that are commonly found among
depressed persons. This extended description, with cases de-
rived from actual patients, provides a clearer understanding of
what we mean by vague terms such as “loss of pleasure” and
“loss of energy.” We also describe the symptoms of mania, a
paradoxical form of depression commonly known as manic-
depression (or bipolar disorder), and include a rating scale for
mania as well. Later in the chapter we turn to mild forms of
depression and of manic-depression.
We want to emphasize again that this is not a self-help book
that will teach people to diagnose themselves. We want to help
people learn the warning signals so that they can decide whether
they should seek a diagnosis from a qualified professional. Indi-
viduals (sometimes aided by their families or others close to them)
are in the best possible position to detect changes—possibly dan-
gerous ones—in themselves. The rating scales and methods of
scoring follow. (For rating someone close to you rather than your-
self, think of how the scale might apply to that person.)
Self-Rating Scale for Depression
Have either of the following symptoms been present nearly

every day for at least two weeks?
A.1. Have you been sad, blue, or “down in the dumps”?
A.2. Have you lost interest or pleasure in all or almost all the
things you usually do (work, hobbies, other activities)?
If either A.1. or A.2. is true, continue. If not, you probably do

not have a depressive illness.
Have any of the following been present nearly every day for
at least two weeks?
1. A poor appetite or overeating? No Yes

2. Insomnia? No Yes
3. Oversleeping? (Going to bed earlier than

usual, staying in bed later than usual,
taking naps?) No Yes
4. Do you have low energy, fatigue, or

chronic tiredness? No Yes
5. Are you less active or talkative than

usual or do you feel slowed down or
restless? No Yes
6. Do you avoid the company of other

people? No Yes
7. Do you lose interest or enjoyment in

sex and other pleasurable activities? No Yes
8. Do you fail to experience pleasure

when you are praised, given presents,
promoted, etc.? No Yes
9. Do you have feelings of inadequacy or

decreased feelings of self-esteem, or are
you increasingly self-critical? No Yes
10. Are you less efficient or do you accomplish

less at school, work, or home? No Yes
11. Do you feel less able to cope with the

routine responsibilities of everyday life? No Yes
12. Do you find that your concentration is

poor or that you have difficulty making
decisions (even trivial ones)? No Yes
If A.1 or A.2 is true, and if you answer Yes to any four of these
twelve questions, you probably have a depressive illness and
should consult a qualified physician. Even if you have only two

or three symptoms, you should seriously consider a checkup.
One reason we say that you probably have a depressive illness
is that some people with these symptoms have a physical ill-
ness such as anemia or low thyroid activity. When you seek
professional help for a possible depressive illness, it is impor-
tant that your physician makes sure that you have a complete
physical checkup at the same time.
The psychiatrist will also try to determine whether you may
be going through a temporary upset due to life circumstances
and do not really have a biological depression.
In deciding whether or not you have depressive illness, you should
try not to give too much weight to what may seem to you to be plau-
sible reasons for your bad feelings. Life is never perfect, and if
people look hard enough, they can find some reason for feeling
bad. Even a major loss, such as a death in the family or a di-
vorce, may not be the real reason for your depressed emotional
state. Furthermore, depressive illness itself may make people
less capable of dealing with life’s problems and may actually
lead to life stresses, such as the loss of a job or the breakup of a
relationship. In such instances what looks like the cause of de-
pression may actually be one of its results. Depressive illness is
often triggered by a real event—the death of a loved one, for
example—but still requires treatment.
Depressive illnesses are easiest to recognize when someone
has a sudden change in his or her emotional state for no appar-
ent reason. People who find themselves saying, “I can’t under-
stand why I feel so bad. There is no good reason for it,” always
need a diagnostic review. However, depressive illnesses may
develop gradually, so that the patient doesn’t see any big dif-
ference between her current emotional state and how she felt a
few years ago. Such a person may think her depressed mood is
simply her normal state—“perhaps I am just a pessimistic and
introverted person.” Even prolonged chronic depressions,
which have been thought of as the person’s normal response to
life, may nevertheless respond to medical treatment.
One rule of thumb involves the length of the period of dis-
tress and the degree of trouble that it has produced. If the dis-
tress has lasted for over a month, or if family, employment, or
social life have been substantially affected, a checkup is highly

advisable. However, even those who have been feeling apa-
thetic for only a few weeks, or who can handle their usual ac-
tivities only by great effort, should also consider a checkup.
There are several sorts of depressive illness, and there are
many different degrees of severity. As we indicated, someone
with depressive illness may not have all of the symptoms in
the rating scale. Nonetheless, if some of these symptoms are all
too familiar, you should not put off getting help.
Therefore, rate yourself on the symptoms with an open mind.
If the rating scale indicates that you may have a depressive ill-
ness, you should get a checkup, regardless of any social or psy-
chological explanations that occur to you.
To provide a more vivid picture of how symptoms of these
kinds affect people’s lives, we present a series of disguised ex-
cerpts from case histories of patients we have treated. Each of
these patients has different symptoms of depression. In indi-
cating how the symptoms manifested themselves in their lives,
we return from time to time to some of the patients to continue
their story because each kind of depression involves a different
combination of symptoms and reveals itself in slightly differ-
ent ways.
Recurrent Problems in Patients’ Illnesses
Loss of Interest
The symptoms of sadness and loss of interest in life are two

highly important aspects of depressive illness. Most people who
are depressed will say they are sad or blue or down in the
dumps. Many will say that they have lost interest in everything.
A few people with a depressive illness are not sad or blue but
instead have widespread loss of interest in their usual pursuits.
These people may not recognize themselves as depressed, but
this symptom is a critical one.
People have a wide variety of interests and pleasures in their
lives—including, usually, simple biological pleasures such as
eating and sex. People also look forward to family gatherings,

sports, vacations, social activities, hobbies, and, in general, to
the possibility that good things will be happening. When they
think of future pleasant events, they usually have a sense of
warm, optimistic hopefulness that is itself already a pleasant
feeling.
Many depressed people lose these warm feelings and expe-
rience a sharp decrease in the ability to have pleasure. The tech-
nical term for this is anhedonia. Activities that used to excite
become boring or unrewarding. Good food may taste like card-
board, and those suffering depression may just pick at their
meals. In severe depression, patients lose the ability to feel and
reciprocate love. They do not experience warmth toward the
people who mean the most to them. In addition, there is a loss
of sexual desire and responsivity. Formerly satisfactory sexual
relationships become unstimulating and burdensome. The de-
pressed individual feels apathetic and unreactive, and may have
a diminished capacity to be close to others.
Mood is a pervasive sustained emotion that markedly affects
our view of the world. Such moods include anger, anxiety, ela-
tion, and depression. Normal mood varies, depending on cir-
cumstances. Rewarding lives result in animated, outgoing
moods. If things turn sour, then mood becomes subdued, cau-
tious, and somewhat indifferent. When things go well again,
the usual good feelings are restored.
Depressed people are different from people whose unhap-
piness is an obviously appropriate response to life circum-
stances. The mood of a depressed person is not in tune with the
environment. Some severely depressed people are completely
unresponsive to what is really good in their lives. It is not un-
common for depressed people to be told that they need a vaca-
tion or a change of pace only to find that, when they go on a
trip, they continue to feel bad.
Other depressed people can be temporarily cheered up. They
will often crave attention and social stimulation because that is
the only way they can lift their spirits and alter their moods.
However, what marks them as having an illness is the fact that,
without continued excitement and praise, their mood slumps.
The cases given derive from actual case histories, with

changes made in identifying details. At times, several cases have
been combined for the sake of succinctness. In all cases, the
symptoms described have been repeatedly demonstrated in the
scientific clinical literature.
5 Jill Jason, a busy young housewife and mother, found

herself increasingly indifferent about her usual activities at
home and in the community. She stopped going to her bridge
club, was bored by television, was unsympathetic to her
husband’s difficulties and triumphs, and just went through
the motions with the children. She complained, “I don’t know
what’s gotten into me. Everything was going so well. Now I
don’t give a damn, and I can’t snap out of it. My son came
home with all A’s on his report card and I couldn’t care less.”
Jill’s mood was particularly bad in the morning. Sometimes

late at night she got a kick out of watching television. But by
the next morning, everything seemed awful again. Her hus-
band began to complain that she never enjoyed anything
anymore, that even her sense of humor had disappeared.
When a doctor told Jill that she had been working too hard
and needed a change of scene, she went to a resort with her
husband. However, the vacation was a total disaster. Jill par-
ticipated in a few activities and then stopped going alto-
gether. She spent most of the time sitting in their room. She
let her husband drag her to the swimming pool a few times
because she had always loved to swim, but now she got noth-
ing out of it.
5 Mary Malloy was a vivacious young receptionist who or-

dinarily loved dating and romance and had had a long string
of boyfriends. After a series of unexpected disappointments,
she found herself less interested in going out. She spent more
and more time alone. She told her friends that life was a rat
race and that she was growing up. However, she was also
losing interest in her work.
Mary was at her best in the morning. She would get up, cook
breakfast, and get to work by 8:30 AM. At that time she en-
joyed applying herself and solving problems. However, by
midafternoon she knew that she was just shuffling papers
around. By the time she was ready to leave the office in the
evening, she could accomplish nothing.
Mary spent a lot of time quietly in bed. However, when

friends came over she would brighten and become animated.
Frequently they tried to talk her into going to a party, to cheer
her up. She usually refused, saying that parties were dull
and there wasn’t any point to them.
Surprisingly, when she did agree to go out, she seemed to

have fun and was almost her old self. But when she got home
she slumped into her low mood again. After one of these
experiences, when her friends tried to persuade her to go to
another party, she said that she wouldn’t go because parties
were boring. Her friends reminded her that she had seemed
to enjoy the last party, but Mary insisted that she really didn’t
feel up to it.
Finally, like Jill Jason, Mary was persuaded to go to a resort

for a change. At first it seemed like the right prescription.
She danced, played tennis, met some new attractive men,
and exchanged phone numbers. Her old zest for life seemed
to return. However, when she went back to the city her level
of interest slowly declined. She didn’t call her new friends,
and when they called her, she saw them a few times but then
let the relationships fizzle out.
5 Milton Meyer was a successful surgeon in his forties who

also enjoyed teaching. He was an avid amateur violinist as
well as an enthusiastic gardener. Long before he noticed any-
thing unusual, his wife observed gradual changes. His in-
terest in surgery lessened and he disparaged his work, saying
that it was not very useful in the long run, that it only patched
things up. He found reasons for avoiding teaching, stopped
playing in his amateur quartet, and hired someone to take

care of his garden. His wife sensed his increasing withdrawal,
but when she asked him whether he was depressed, he de-
nied it. In terms of how he felt, he was being honest. He was
not sad, blue, or down in the dumps—he had just lost inter-
est in everything.
5 Sally and Jane Harris were cousins who had led charmed
lives. Their fathers were brothers who had maintained close
personal and business ties, their families were warm, stimu-
lating, and protective. Their economic circumstances were
excellent, and both families could afford to send the young
women to the best schools, where their fine minds showed
themselves to good advantage. Sally decided to become a
doctor and Jane to become a lawyer. They both worked hard,
achieved recognition, and made very favorable careers. They
had deferred marriage to continue their advanced educa-
tion, but both had long-term intimate relationships and both
eventually did marry, once life’s circumstances had solidi-
fied and they had achieved their career goals.
When the cousins were in their early thirties, their fathers,

traveling together on a business trip, died in the crash of a
small commuter plane, leaving the entire extended family
crushed and bereft. Both Sally and Jane cried for days; they
sat around brooding, preoccupied with their loss, thinking
excessively and painfully of their fathers. Their mothers too
were racked with acute grief. Whenever the family got to-
gether, they would immediately start to cry without saying
a single word.
Despite their torment, both women rose to the occasion and

continued to go to work, to carry out their professional du-
ties, to take care of their patients and clients, to supervise
their households, to love and care for their husbands and
children. All this was uphill work, but they did it. More-
over, with time, both found that immersing themselves in
everyday details was a consolation, as it distracted them
from their constant gnawing grief. Both learned that the best
medicine for their grief was turning their minds outward
toward activities.
After some three months, Sally’s emotional life had pretty

much resumed its former richness, though punctuated by
occasional waves of longing for her dead father. Jane on the
other hand, when she talked to Sally, told her that she never
thought about her father any more. As a matter of act, her
formerly active imagination about both the good and bad
things in her life seemed somewhat dulled. Previously, she
had spent a great deal of time reading law journals to be
sure that she was absolutely on top of current decisions, but
lately she had let this slide.
Loss of Energy
Most of the time people have a feeling of zest, of get-up-and-

go. When things interest them, they feel energized and will
pursue their goals actively. Depressed people feel as if they have
run out of gas. They complain about fatigue, feel that every-
thing is an effort, that they just can’t get going, that their body
feels heavy or leaden, that they are listless and slowed down.
They find themselves unable to achieve their usual goals.
5 Jill Jason started to complain that she was weary all the
time. She was usually efficient and well organized, but now
she procrastinated with her work, putting off tasks that had
to be done around the house. Because of her lack of interest
and lack of energy, she became progressively withdrawn
socially. When her friends told her that she needed vitamins
or a tonic, she tried them, but they didn’t help.
5 Mary Malloy expected to hear from her remaining boy-

friend one Friday about weekend plans, but he didn’t call.
Suddenly she was overcome by overwhelming fatigue. Her
body felt made of lead. Previously she had been uninterested
in making a special effort to engage in various activities, but
now she felt physically incapable of moving. She crawled

into bed, where she spent the entire weekend eating Oreos.
5 Sally Harris had resumed her meaningful 60-hour work

week, dividing her time between her private office, the clinic
that she worked in, and the hospital. Although she com-
plained about work, it was in a good-humored spirit and, in
fact, her heavy schedule was almost entirely self-imposed,
not because of financial need but rather because of a deep
interest in her work and patients.
5 Jane Harris also was used to working overtime. In fact,

her legal firm billed their clients by actually monitoring time
spent working on each case. They had an intricate system of
clocking on and off time spent reading, conferring, writing,
on the phone, in court, etc.
Jane was somewhat surprised, although it did not come as a

complete shock, when her boss pointed out to her that her
billings were falling off. Peculiarly, during the period of her
intense grief, her billings, if anything, had gone up as she
had plunged into her work to ease her pain. Now, although
still productive, she just was not putting in as much time as
before. She told her boss that maybe she was suffering from
a mild case of burnout; legal technicalities that formerly in-
trigued and challenged her now seemed somewhat dull and
routine. Furthermore, she just didn’t seem to have the zest
for it anymore. When she looked at the work piled up in her
in-box, she began to feel oppressed rather than assertive
about her capacities to deal with difficult work.
Appetite and Weight Disturbances:

Changes in Eating Patterns
For most people, food is one of the greatest pleasures. It is com-

mon knowledge that appetite disturbances accompany all sorts
of illnesses. This seems particularly true of depression. Some
people eat more when depressed, and some eat less.
5 Mary Malloy spent a great deal of time at home alone as

she became more withdrawn. She watched television and
ate junk food. She had a particularly strong craving for
sweets, carbohydrates, and chocolate. She gained fifteen
pounds, which added to her feelings of self-disgust and her
unwillingness to try to be socially active. At times she would
stuff herself with so much candy that she would force her-
self to throw up to relieve her bloating. Mary had read some
pop psychology that told her that she was acting infantile
because eating was the only way she could feel loved.
5 Jill Jason, in contrast, just pecked at her food. She said

that nothing tasted good and ignored even her favorite
dishes. Her husband told her that she would get really sick
if she didn’t eat, so she would make a real effort to get some-
thing down every day. To her, eating was a chore, and at
times she just couldn’t do it. She was getting very thin.
Sleep Disturbances
People differ in their need for sleep and in their sleep patterns.
Temporary difficulties in falling asleep, particularly when un-
der tension, are common. Some people experience various pat-
terns of broken sleep, commonly referred to as insomnia. But
many depressives fall asleep with ease only to have restless
sleep and early morning awakening. Others seem to require
remarkably large amounts of sleep. Although it is clear that not
everyone with sleep irregularities is depressed, changes in sleep
patterns frequently accompany depressions and are a vital
warning sign.
5 Jill Jason, although fearful and upset, had little difficulty

falling asleep. As a matter of fact, she welcomed sleep since
it gave her some relief. Nevertheless, she would awaken sev-
eral times in the middle of the night and feel awful. Her
gloom and feelings of hopelessness were at their worst. Af-
ter much tossing and turning, she would eventually fall back
to sleep. Finally, at five in the morning she would awaken
and find it impossible to go back to sleep even though she

felt exhausted.
5 Mary Malloy, as she became less and less interested in

her life, was sleeping more and more. When working, she
had waves of fatigue and sleepiness that prevented her from
doing her job properly. Finally, she quit work and stayed at
home, where she took frequent naps or simply dozed in bed
all day. She explained her behavior by saying she was re-
treating from reality.
Other Physical Symptoms
Periods of pain and bodily distress are usually signs of illness.

Most such difficulties are temporary, and people usually shrug
them off or take it easy for a while until they go away. If suffi-
ciently distressed they may seek medical attention.
The tendency to seek medical attention is quite variable.
Some people consider it a sign of weakness to seek help or to
complain, so they minimize their difficulties and discomfort
(they “tough it out” in a stoical way). Others find their distress
too difficult to bear alone and frequently turn to friends, fam-
ily, clergy, or doctors for help.
Most people can’t stand the idea that they may have a dis-
turbance of their emotions or feelings, since they think that
would label them as crazy. Therefore, when they are in distress,
they find it far easier to believe that something is physically
wrong with them than to recognize that they are having emo-
tional problems.
5 Jill Jason’s husband was losing patience. He finally told

her that if she didn’t go to her family doctor her would drag
her there. Jill then told him that she thought she might have
cancer. She had all these weak feelings and was losing weight.
Every once in a while she felt funny all over, as if she might
faint. She had been brooding about the possibility of cancer
for several months but was afraid to mention it because that
might make it come true. She was afraid to find out what the
doctor might discover.
When she finally went for a physical examination, her doc-

tor found no signs of cancer or any other physical illness.
Although she was obviously haggard, underweight, and
miserable, he told her that there was nothing wrong with
her and that she should buck up, pull herself together, and
stop feeling so sorry for herself. On the way home, Jill said
that she still thought she had cancer and that the doctor had
missed it.
5 Mary Malloy thought that she had heart disease. Every

once in a while her heart would go a mile a minute, and she
would feel as if her head was floating off her shoulders and
that she might fall down any second. Several times she had
such difficulty in catching her breath that she thought she
was dying and went to an emergency room. They told her
that her heart was fine and it was just her nerves.
One doctor suggested that she take tranquilizers for her at-
tacks of panic, and, after much hesitation, she took some.
They seemed to help slightly, but she was still weary, fa-
tigued, and socially isolated; occasionally she again thought
she was having a heart attack. Her family thought she was
playing for sympathy.
5 Bob Bush, a successful producer of Broadway shows, for

no apparent reason, developed a low-grade, chronic belly-
ache. Sometimes he would feel as if he had diarrhea and
would suddenly have to rush to the bathroom. He found
himself so preoccupied with this that he was not doing jus-
tice to the theatrical enterprises he was producing. Wher-
ever he went, the first thing he would do was check out where
the bathroom was. He began to avoid long trips. His social
life became progressively more constricted as he made ex-
cuses not to go to places where he would not have ready
access to a bathroom.
Bob went to many different doctors, who all told him that
there was nothing wrong with his physical health and that he
was being silly. He began to feel sad and withdrawn but

blamed this on his physical troubles.
5 Saul Schwartz, a middle-aged businessman who usually

enjoyed life, said there was nothing wrong with him even
though he hadn’t worked for the past two months. He didn’t
see what all the fuss was about because it was his terrible
backache that kept him from working. The doctor had told
him that he couldn’t find anything wrong with his back and
that he was sure the pain would go away in time. Saul was
simply waiting for the pain to go away. His married son,
David, kept telling him that something must be wrong be-
sides his back because he wasn’t even reading the newspa-
pers anymore and he had gotten very quiet.
David was worried because when he persuaded his father

to come out for a ride or to go to the movies, Saul didn’t
enjoy himself. Who would enjoy themselves if they had a
bad back? Saul had never been a complainer and he wasn’t
complaining now. He didn’t even talk about his back. He
only mentioned it when people told him he should be trying
to do more. Saul’s wife asked him whether he was depressed,
because he seemed so blue and quiet. Saul said that he wasn’t
sad or blue but was just quiet because of his back.
Decreased Sexual Drive
5 Jill Jason and her husband had been passionate and sexu-
ally involved in the first few years of their marriage. With
time, the frequency and fervor had diminished some, but
the gamut of sexual activity from casual caresses through
lovemaking was still central to their lives. Both looked for-
ward to vacations knowing that the break in routine would
be heightened by a burst of renewed ardor.
As Jill steadily lost interest in her usual activities, she showed

less enthusiasm for sexual intercourse. Her husband sensed
that she seemed to feel that their previously enjoyable sexual

relationship had now become an unpleasant chore. An at-
tempt to renew the honeymoon spirit by taking a long week-
end trip was a miserable fiasco. Jill said she wasn’t just dead
sexually, she was dead everywhere.
Restlessness or Slowing Down: Changes in

Movement and Speech Patterns
Everyone has an individual pattern of speech and motion. Some

people are quiet, whereas others talk a lot. Some people are ac-
tive and restless, while others can sit contentedly for long peri-
ods. Depressive illness often markedly changes these patterns.
5 Jill Jason was getting quieter and quieter and more and
more immobile. Her family would find her sitting for hours
in a chair, looking blankly at the wall. When they asked her
how she was feeling, she seemed at first not to hear them,
but after a marked delay she spoke a few words in a weak
voice. She said nothing spontaneously. Her family thought
she just wanted to be left alone, so they left her alone.
5 Peggy Pearl, a wealthy, middle-aged housewife with an

active social life, couldn’t stop talking or pacing. As her hus-
band came through the door, she assailed him with com-
plaints about herself, about him, about the neighbors and
the family. She felt so bad that he had to do something im-
mediately because she just couldn’t go on like this. She ner-
vously paced around the apartment wringing her hands and
picking at her cuticles. At times she got so upset that she
pulled her hair out.
Self-Reproach and Guilt: Loss of Self-Esteem

and Painful Mood and Thought Content
Low self-esteem is usually not recognized as one of the most

common symptoms of depression. On the whole, most people
think well of themselves. Most people know that they are not
extraordinarily charming, not strikingly handsome or beauti-

ful, not brilliant or talented, but they are satisfied with them-
selves anyway. They can usually think of something they’re
good at and somebody who wants to be with them. Despite
current popular ideas to the contrary—fostered by television
talk shows, movies, books, and magazines—most people are
optimistic and adaptable, even under difficult circumstances.
If someone has failed to reach his goals, or has been rejected
or put down by loved ones, that may result in temporary bad
feelings about himself. But such feelings rarely last long, and
they usually force the person into some form of constructive
activity.
Since depressed people view the future pessimistically and
are unable to respond positively, even to good news and stimu-
lating activities, it is not surprising that many conclude that it
is all their fault and they are ineffectual losers. Such feelings
are often explained psychologically on the grounds that such
people must have been treated badly by their parents, who left
them with permanent psychological scars.
The wretched mood that characterizes depressives is often
accompanied by negative emotions and thoughts about them-
selves. They may brood about their failures and feel worthless
and self-critical. These feelings may become so painful that the
depressed person simply cannot stand herself and is plagued
by thoughts of guilt over past failures. She begins to feel that
she is being punished and should expect punishment, and that
perhaps she would be better off dead.
The intense painfulness of many depressions is difficult for
the ordinary person to appreciate. Therefore, when a depressed
person tries to communicate about how bad she feels, she is
often criticized because it looks like some sort of act or put-on.
5 Jill Jason told her husband that she thought she was a
terrible person and a failure as a mother and wife, and then
she cried bitterly. Initially sympathetic, her husband told her
that he loved her, that the whole family loved her, and that
everyone thought she was a wonderful person. At first this
seemed to help her, but the next day she felt as bad as ever
and complained constantly again.
After a while Jill’s husband became thoroughly irritated. No

matter what he said or did, it didn’t work, leaving him feel-
ing helpless and overwhelmed. At times he got quite angry
at her. “Why are you behaving this way? You’ve had every-
thing anyone should want.” He couldn’t help feeling that
his wife was like a bottomless pit that nothing could fill.
5 Jane and Sally Harris frequently met to talk over their

families and friends and inevitably their common loss. Slowly
the tenor of their conversation shifted. Sally reminisced about
her father and the good times they had, how helpful he was
to her, the pride he had taken in her and his understanding
ways. She was filled with thoughts of her loss. Jane, on the
other hand, talked less and less about her father and more
and more about how bad she felt, how uninteresting her
work had become, and how she was feeling more and more
guilty about letting her family and her boss down. When
she did talk about her father, she would often dwell upon
how she should have been a better daughter. Sally would
point out to her that her relationship with her father had
been just great, but Jane didn’t see it that way.
Poor Concentration and Indecisiveness:

Mental Difficulties
Many people have small fluctuations in their ability to concen-

trate. When fatigued, they find it more difficult to concentrate
and to stay focused. Depressed people have many complaints
about their mental functioning. They feel that their memory is
shot and that they cannot pay attention. In addition, they often
behave in an extremely indecisive and perplexed fashion, as if
they just can’t figure things out.
Most nonimpulsive people deliberate carefully about major
decisions, such as whether to accept or quit a job, or whether or
not to get married. Indecisiveness is a symptom of depression
when individuals cannot make up their minds about relatively
trivial matters. An example would be a woman who is about
to go out to dinner with friends but who delays the group’s
departure for half an hour because she cannot decide whether

she wants to eat at a French or Italian restaurant.
5 Jill Jason had been the mainstay of her church group.

When a social event or dinner had to be arranged, she was a
take-charge, get-it-done person. Now when she was asked
to organize a church supper, she felt completely over-
whelmed. She couldn’t decide whether she should do it or
not and kept wavering back and forth. When her husband
told her with exasperation that she had managed such events
ten times before without trouble, she stared at him blankly
and started to cry helplessly. Jill’s husband told the church
group that she couldn’t do it, hoping that she would feel
less burdened, but that didn’t help, either. She persisted in
feeling overwhelmed, incompetent, and indecisive.
Deterioration of Social Relationships
Most people have a network of friends and family members

whom they depend on for help when trouble strikes. Typically,
they rely on little informal mutual-aid societies and get much
of their joy in life from their friends and lovers. Depression sabo-
tages these relationships, so that family and longtime friends
begin to drift away.
5 Jill Jason had stopped going to bridge parties. At first

her friends came to visit, but she was silent and unrespon-
sive. When they would joke with her, trying to cheer her up,
she didn’t crack a smile, When they told her that she’d be all
right soon, she just shook her head. She didn’t return their
calls and visits, and after a while they rarely called. Her hus-
band started to stay out late after work because her dissatis-
faction with everything made him feel helpless and
frustrated.
5 Mary Malloy still enjoyed her relationship with her boy-

friend. Because that was the only real source of pleasure that
she still had, she became very greedy and demanding about
it. When her boyfriend told her that he would call her at 9:00
PM but called at 9:15 because his train had been delayed, she
burst into tears and told him that he couldn’t treat her so
cruelly. He should know how bad she felt and how much
she looked forward to seeing him and how her whole life
depended on him and his love for her, and where would she
be without him? Under such pressure he eventually stopped
seeing her.
5 Peggy Pearl got nasty. She told her husband that it was
all his fault that she felt so terrible and that everyone had let
her down. She complained incessantly that nobody loved
her or wanted her or paid any attention to her. After a while
she was right.
5 Jane Harris had managed to be a superwoman by many

people’s standards. She had a successful career, a happy
home life, and wide circle of friends and activities. People
would wonder at her remarkable ability, vivacity, and charm.
Lately, however, things had been narrowing in. She wasn’t
working as hard, entertaining as much, or livening her fam-
ily with good-natured banter. She was quieter and the social
circle was steadily constricting. She called on fewer and fewer
of her friends, accepted fewer and fewer social engagements.
Several of her friends said that it was no surprise to them,
after all she had set herself an impossible task in life. Her
growing depression was not perceived as an impairment of
her truly extraordinary ability, but simply as what could be
expected from anyone.
5 Sally Harris, in contrast, was still functioning at the same

high level. She had an argument once with one of Jane’s
friends when Sally mentioned that Jane seemed to be doing
poorly. Jane’s friend said that it was not doing poorly to be
working and running a household. Sally pointed out that
you couldn’t compare Jane with the average person because
she wasn’t average to start out with. Jane’s impairment was
only made obvious when you compared her current func-
tioning with her former vibrant outgoing self. Jane’s friend
was unconvinced, Jane’s life still looked pretty good to her.

Sally, however, was getting more and more worried about
her cousin.
For both Mary and Peggy, depression led to increased de-

mands that could not be satisfied, and it drove others away.
Jill’s unresponsiveness had the same effect. But Jane’s de-
pression went undetected, except to her cousin Sally.
Increased Use of Intoxicants and Drugs
Alcohol and more recently marijuana are commonly consumed

for recreational purposes. Most people can use these sub-
stances in moderation without too much difficulty. However,
many people are unable to control their consumption of li-
quor and drugs, developing patterns of overuse that may de-
stroy their lives.
Why some people can remain social drinkers while others
become alcoholics is not fully understood. At least part of the
answer is that some are suffering from depression and are us-
ing alcohol or marijuana as mental anesthetics and tempo-
rary distractions. They are really attempting to medicate
themselves. However, because these substances do not lift the
depression, they increase their consumption of them in their
search for relief.
5 Peggy Pearl’s husband was astonished one night when

he came home to find Peggy drunk. He and Peggy often had
a couple of drinks, but the only time he had ever seen her
drunk was after a big New Year’s Eve party. He certainly
didn’t think that she ever drank during the day.
When Peggy sobered up she told him that she had just felt
so bad that day, so lonely and isolated, that she thought
maybe a little drink would help her out, and indeed it did.
However, she hadn’t expected to polish off the whole bottle.
She said she wouldn’t do it again, but she did, and increas-
ingly often.
5 Ralph Rogers, an outstanding high-school student, was

the pride of his family. He was captain of the high-school
football team and near the top of his class. Everyone knew
that Ralph had a big future ahead of him. Then Ralph’s marks
began to slip. He said that it was hard for him to concen-
trate, but actually he was spending less time at his studies.
His teammates started to complain about him because his
judgment on the field seemed impaired. He called the wrong
plays and didn’t respond rapidly when the other team tried
something new.
Ralph began to hang out with a different crowd who used

drugs. In time, he began to use marijuana steadily and started
to cut classes. The school principal finally called his parents
in and told them sadly that Ralph seemed to have a drug
problem.
Vocational Failure
In the same way that Ralph Rogers dramatically manifested a

loss of competence in his school activities, prosperous business
executives and hardworking professionals may also suddenly
become ineffective.
5 Richard Rogers, Ralph’s father, a prosperous sales man-

ager, was upset about his son’s difficulties. He felt that some-
how he had let Ralph down and was to blame. At work he
became lost in guilty ruminations. Previously decisive and
energetic, he now had trouble making up his mind about
everything. His co-workers, who depended on him, became
very dissatisfied, and finally his boss told him that he’d bet-
ter snap out of it.
Richard tried without success to return to his previous level

of functioning. He knew that brooding about Ralph’s diffi-
culties did his son no good, and wasn’t helping him either,
but he just couldn’t stop it. He was starting to wake up at
night, and his appetite was vanishing.
Hostility and Irritability
Some people think that an inability to express anger causes

depression. They even argue that depression is anger turned
back against oneself. This particular theory ignores the fact that,
in the midst of depressive periods, many people are far more
irritable and angry than usual. Moreover, their irritability may
get worse when such people suspect that they may be suffer-
ing some emotional problem but are not yet read to admit it.
5 Richard Rogers had always been easy to work for. He

rarely snapped at anyone, and even when he had to chastise
one of his salesmen for goofing off, he always did it in a
straightforward way. He didn’t angrily bawl out the sales-
man but simply tried to change his bad habits and improve
his productivity.
Lately, however, he was barking at everyone. Even the slight-

est error, of no real consequence, provoked a tirade. His sec-
retary of 20 years finally told him that he was causing a lot
of trouble. She was shocked when he told her to shut up and
mind her own business.
5 Peggy Pearl was becoming impossible to live with. Ev-

erything caused an argument. She was upset when her chil-
dren didn’t visit and berated them over the phone. When
they did visit, she yelled at them for not visiting more often.
Peggy fired her longtime maid, accusing her of getting uppity.

She fired the next maid because she couldn’t learn fast
enough where things were. She fired still another maid be-
cause she didn’t like her expression. She spent a lot of time
talking about how you can’t get decent help anymore. When
she and her husband went to restaurants she often got into
embarrassing fights with the waiters, saying the food was
never any good. Her continued excessive drinking made her
temper even worse.
Peggy’s husband, Bob, told her that he thought that some-

thing was definitely wrong with her. She used to be so sweet
and helpful, but now she complained about others all the
time. Peggy said that she had every reason to complain be-
cause she had discovered how lousy everyone was, includ-
ing her husband. Look at the way her so-called friends had
stopped calling her.
When Bob dragged Peggy to the family doctor, the doctor

said that there wasn’t anything obviously wrong with her,
but since she had felt so bad for a year now, maybe she ought
to see a colleague of his for a consultation. When Peggy asked
what the colleague’s specialty was, the doctor answered that
she was a nerve doctor.
“You think I’m crazy,” yelled Peggy. “No.” said the doctor, “I
just think you might need a little help in getting yourself to-
gether.” “You want to put me away,” Peggy whimpered. “I’m
crazy.” “Look Peggy,” said the doctor, “we just want you to
talk with somebody for a while. It will help you feel better.”
Peggy said that she would think about it, but she didn’t go.
Distortion of Reality
Our moods color our understanding of the world and ourselves.

When we feel down, the world seems less satisfactory, and we
seem less admirable. When we are up, the world is an interest-
ing place, and we think we’re pretty good. Depression causes
major distortions in our perception of reality, and therefore
makes handling our problems even more difficult.
5 Richard Rogers went into a real funk when his boss told
him that he better snap out of it. He finally told the boss that
he was quitting because he couldn’t stand letting everyone
down. The boss was astonished. He told Richard that he only
meant that Richard should get some help. He added that
Richard had been one of his best workers for many years,
and he certainly had no intention of firing him. Richard re-
peated that he just wasn’t up to it, thinking that he would
surely be fired soon, he stopped going to work.
Dealing with the Future: Hopelessness,

Suicidal Thoughts, and Suicide Attempts
When normal people think about the future, their feelings are a
mixture of pluses and minuses. When they think about past
happy events or imagine pleasant future possibilities, they have
positive, warm feelings of recollection or anticipation. Many of
us spend a lot of time daydreaming, which is nothing more
than making ourselves feel good by thinking that the future
might work out in ways that we would like. Such daydreams
are often constructive since thinking about possibilities that
produce good feelings may stir one into related realistic activ-
ity. This is what we mean by saying that a person is in a hope-
ful frame of mind and acting in an enterprising way.
When people think about past unhappy events and possible
future difficulties, their mood is taken over by tension and ap-
prehension. However, sometimes when they perceive trouble
coming and feel anxious about it, they are also stirred into useful
action. They think about possible maneuvers that will prevent
the trouble from occurring or will at least remove them from the
scene of probable pain. Once people have figured out a good
strategy for avoiding impending trouble, their sense of hopeful-
ness returns and they attempt to carry out their protective plans.
The depressed person has a marked decrease in the ability
to remember and imagine pleasant thoughts. When he thinks
about the future or the past, all he focuses on are the minuses.
The pluses don’t get through or are greatly reduced. Therefore,
depressed persons cannot feel pleasant hopefulness.
A severe inability to feel optimism may lead to suicide. Since
our attempts to deal with the future are steered by our hopeful
thinking, the depressed person’s loss of hope prevents him from
planning constructively. He feels overwhelmed and helpless.
When this feeling becomes too painful, many depressed people
feel they would be better off dead. They would no longer be a
burden to their family and they would no longer have to suffer
such pain. Sometimes when they express such feelings, family
and friends tend not to take them seriously. It is commonly
thought that people who talk about suicide don’t actually take
their own lives, but this is simply not true.
5 Gil Green thought that he was a total failure. Although he

had been an expert technician for many years, he became con-
vinced that the new technology was just getting too difficult.
He couldn’t work and stayed home, brooding and spending
much of his time in solitary drinking. One day he told his
wife that he would be better off dead, but when she became
upset, he hastened to reassure her that he didn’t mean it. How-
ever, a week later he repeated the threat while intoxicated.
Frightened, his wife insisted that he see a doctor.
Gil told the doctor that it was just the liquor talking, that he
was just kidding and that being out of work would upset
anybody. The doctor did not spend the time to review Gil’s
feelings in depth. In particular, he did not inquire as to Gil’s
sense of hopelessness, inability to enjoy himself, sleep dis-
turbance, and increasing use of alcohol. He hurriedly sug-
gested that Gil take a tranquilizer. A few days later, Gil’s wife
came home from a trip to the grocery store and found him
hanging from a basement beam. His suicide note said that it
wasn’t her fault but that the future was hopeless and that he
couldn’t stand letting everybody down.
Depressive Reactions to Threatening Life Events
The patients described here, despite their differences, all have

in common depressive symptoms that do not seem related to
disastrous life events. In the two examples that follow, the de-
pressions followed unfortunate life circumstances. Neverthe-
less, these depressions differ qualitatively from each other, as
we will explore when we look at the treatment of these patients.
George Gelb, and others who are discussed here, came to a
university depression clinic to participate in a study that was
evaluating a new experimental antidepressant. The way such
studies are done is that the patient may receive, without know-
ing which, either the new experimental antidepressant, or a
standard antidepressant, or a dummy pill, which is called a
placebo. Doctors who evaluate the effects of the treatment also
do not know which pill the patient is receiving. The reason for
this is that some people will get better because their depression
is improving on its own or because they respond to the simple
fact of receiving help. Including the placebo pill allows the doc-
tors to find out how many of their patients would have gotten
better without specific treatment. Comparing the effects of the
standard antidepressant tells one how much benefit that drug
produced over and above the effects of just receiving a placebo
and coming for help. The experimental antidepressant can then
be compared both with the standard antidepressant and the
placebo to see if it is effective and whether it is better than usual
treatment.
5 George Gelb was a 51-year-old high-middle management

executive in a large corporation. He came to a depression
clinic to participate in a study comparing the effects of a pla-
cebo, a standard antidepressant, and an experimental anti-
depressant. For several years his marriage had been
deteriorating, and a few months earlier his foreign-born wife
had informed him that she planned to return to her native
country, taking their 14-year-old daughter and as much of
their money as she could get. Shortly thereafter, his corpora-
tion had decided to reduce output by 75 percent. George
would be laid off, receiving only a few months’ pay. His
management job was so specialized that he doubted whether
he could find another like it.
At the first interview, the psychiatrist saw a middle-aged man

whose lined face and slow-moving, bent-over posture re-
flected his inner state. In a voice filled with tears he described
his marital and vocational disasters. The symptoms were
typical: guilt, pervasive loss of interest, great fatigue, seri-
ously disrupted sleep, appetite and weight loss. Severely
depressed, George was entered in the drug study.
5 Carl Carr, a 31-year-old computer repairman, contacted

a psychiatrist approximately a year and a half after the de-
velopment of a depression. His computer-repair work in-
volved being in South America for periods of three to four
months followed by periods of about the same length in the

United States. The depression had developed after he had
sustained a hand injury that interfered with his ability to
perform his job. Despite excellent medical care, the injury
was recovering so slowly that he could not work.
Prior to his injury Carl had been a hardworking and compe-

tent young man who had many friends and married early.
His major psychological difficulty had stemmed from his
divorce. During his work-related travels his wife had gone
through law school and had begun to feel that their lives
were now too different. The marriage had been unexciting
but had seemed stable, and Carl was surprised when his wife
asked for a divorce. They tried marriage counseling, but it
did not save the marriage. A few years later Carl fell in love
with another woman, whom he planned to marry.
Following the injury Carl had vivid flashbacks of the acci-

dent and noted that he was becoming increasingly anxious
and depressed. He returned to school in order to retool by
obtaining another degree. For the first time he found school
difficult and his concentration and memory impaired. He
also began to have episodes of dizziness, light-headedness,
and palpitations.
In seeking help, Carl first consulted a group of nonmedical

psychotherapists, who recommended hypnotherapy along
with “reality therapy” and “rational emotive therapy.” He
was perceived as depressed, but they recommended that
antidepressants not be given because of the possible nega-
tive effect on his concentration. During the next year and a
half he received intermittent psychotherapy while his con-
dition worsened. His grades at school fell, he became anx-
ious when he left the house (agoraphobia), and his self-esteem
diminished “to the vanishing point.” His psychological prob-
lems were worsened by his physical ones. His injured hand
could not be repaired sufficiently to allow him to return to
his job. At this point he consulted a psychiatrist.
Grief
In mentioning depressive responses to life events, it is impor-

tant to discuss grief. Grief and mourning are normal psycho-
logical responses to the death of a loved one. Psychiatrists see
the mourning process—thinking of, talking of, recalling expe-
riences with the deceased—as a necessary part of healing. The
pain and the attempt to deal with it enable the bereaved to be-
gin to separate himself or herself from the deceased, to re-enter
life, and to develop the ability to form new relationships.
In normal grief or bereavement, a person manifests symp-
toms very similar to those of biological depression, but there
are some differences. Studies of the bereaved have shown that
their most common symptoms are depressed mood, crying
spells, insomnia, and weight loss. These symptoms are indis-
tinguishable from those of depressive illness. One major and
obvious difference, of course, is that the bereaved perceive their
feelings as normal and comprehensible, and, for most, their
functioning is unimpaired. The bereaved do not feel guilty, or
if they do, their guilt is chiefly about things they wish they had
done or not done preceding the death of the loved one. In gen-
eral, the bereaved do not markedly slow down physically and
mentally, and they do not experience decreases in self-esteem
or increases in self-criticism. They may entertain thoughts that
they would be better off dead or that they should have died
with the deceased, but they are not preoccupied with thoughts
of suicide. In some instances prolonged grief may merge into
biological depression.
There is disagreement among psychologists and psychiatrists
about how long “normal” bereavement should last. In general,
if severe grief leads to progressive inability to function, grief
may have developed into clinical depression. Some psychia-
trists believe that antidepressant medication relieves the symp-
toms of “pathological grief,” although antidepressant
medication is ineffectual during the normal grieving process.
5 Jane and Sally Harris went out for lunch one day, and
Sally observed that Jane was just picking at her food. Jane
had gotten quite thin recently, and Sally finally decided to

tell Jane of her concerns. She pointed out that Jane had slowed
down, was hardly talking, had lost her sense of humor, and
was becoming more and more isolated from her friends. Sally
didn’t know that Jane’s work was not up to her former stan-
dards either. Sally asked Jane whether she was still grieving
for her father and told Jane that she still cried at least once a
week, thinking of her dad. Jane shocked her when she said
that not only didn’t she think about her father but that she
couldn’t cry. At times, she wished that she could cry, but
rather than feeling pain, she felt empty. At that point, Sally’s
medical training took over and she suddenly realized that
her cousin was not simply grief-stricken but had become ill
with a major depression. That her illness had been triggered
by a real-life loss was certainly true, and that Jane had never
shown any sign of a previous predisposition to depression
was also true. Nonetheless, Jane had passed beyond grief
and now required medical care.
Jane told Sally that, as the product of an excellent upper-

middle-class education, she had learned that emotional ill-
ness came from unconscious conflicts over repressed sexual
and aggressive urges. In her readings, Jane even discovered
that psychoanalysis taught that severe depression after the
loss of a loved one was due to unconscious hatred for the loved
one, which was now turned back against oneself. Further, she
had read about antidepressants but thought that they were
something like alcohol or tranquilizers, drugs that would just
simply dull your senses and obliterate painful memories. Tak-
ing a pill was clearly second-class care that meant that you
were just sweeping your troubles under the rug.
Jane told this to Sally and was surprised when her dear friend
and cousin told her that she was nearly 40 years behind the
times. Jane was especially surprised because she had con-
sidered herself a well-informed person who kept up-to-date
by reading the best newspapers and magazines. They were
full of articles describing psychological causes for emotional
disturbance wholly dismissing biological approaches as
crude and naïve. Sally told Jane about a colleague who spe-
cialized in depression and medication and insisted that she
be evaluated immediately.
Long-Term Depression
The following case differs from the others in the long-term na-
ture of the illness, which had been misdiagnosed in the patient’s
earlier years.
5 Edith Ebel, a 50-year-old married professional, was a par-

ticipant in a drug study with a new antidepressant medica-
tion. She had been depressed for approximately ten years
and had received two rounds of psychotherapy during that
time. As a child and adolescent, she had had symptoms that
were a first considered neurotic, the result of growing up in
a difficult family.
Edith had been the oldest of four girls raised by a mother

described as spoiled, demanding, and greedy, who became
an alcoholic during the patient’s early childhood and ado-
lescence. The mother apparently did not feel and certainly
did not express warm or loving feelings. She punished the
patient with sarcasm and contempt. No help was available
from Edith’s father, who was a psychological absentee—he
showed no interest in her.
The family lived in the country, and Edith had few friends—
although those she had were close and she valued them
highly. She dealt with the family situation by withdrawing
and by mostly reading. A tall woman, she had gone through
a particularly gawky adolescence, accurately described her-
self as unattractive, and did not begin to date until she en-
tered college. Nevertheless, she made a fine marriage to a
thoughtful, caring, and loving man.
Edith functioned well on a number of jobs and ran a ship-

shape home. Her other major interest continued to be read-
ing, and she also played some golf. She felt that she had been
programmed to achieve and on her job was very competi-

tive and sarcastic (she was aware of the irony of being like
her mother), feeling adequate only when she could put down
her peers. Unhappy at this situation, she finally entered psy-
chotherapy.
At some time during her first psychotherapy, the quality of

her mood changed. She lost interest in golf, her sex drive
diminished, her irritability increased, and she began to be-
have unpleasantly to members of her family as well as to co-
workers.
The two courses of psychotherapy, which together consumed

more than three years spread out over almost a decade, con-
vinced her that her problems were the result of her experi-
ences, but she remained irritable and competitive, and still
had few interests in life.
Mania
It is relatively easy to understand that depressed people are

sick. They look miserable and often function poorly. Yet,
strangely, many depressed patients at times feel excessively
good. These periods are called “manic episodes,” and some-
times manias occur when the patient has never been depressed.
A person is considered manic if she (1) has a prolonged period
during which she is euphoric, elevated, “flying”; and (2) has a
number of the following symptoms: inflated self-esteem, or the
feeling that she is better, wiser, superior to others; a markedly
decreased need to sleep (for example, managing on a few hours
a night); a tendency to monopolize conversations, talking rap-
idly and excessively; the feeling that her thoughts are flowing
so rapidly that she cannot express them in an orderly fashion;
increased activity—socially, at work or school, or sexually; im-
pulsive behavior that often leads to trouble, such as buying
sprees, promiscuity, and rash business decisions. Manic peri-
ods can be variable in duration, and frequently they are fol-
lowed by severe depression, so that this combination of
symptoms is commonly known as manic-depression.
Unlike the situation in depression, the manic patient, par-

ticularly if his mania is mild, may not recognize that he is ill.
He perceives himself as enjoying life more than he ever has
before, but those who know him often suspect that something
is wrong. Before discussing mania, we will present the mania
self-rating scale.
Self-Rating Scale for Mania
A1. Are you experiencing a distinct period of abnormally

elevated and euphoric mood or unusually irritable and
angry mood?
A2. During the period of mood disturbance, have you had

any of the following symptoms?
1. Are you experiencing increased self-esteem

or possible overevaluation of your abilities,
achievement, or position in the world? Yes No
2. Do you have a decreased need for sleep?

For example, if you ordinarily need 7 or 8
hours to function well, do you find that now
you can feel perfectly alert and energetic on
3 or 4 hours sleep? Yes No
3. Are you increasingly talkative and do you

feel an inner pressure to keep talking (or an
inability to stop talking when it would be
appropriate to do so)? Yes No
4. Do you find yourself rapidly shifting your

conversation from one topic to another
beginning on “X,” taking off from that to
“Y,” taking off from that to “Z,” etc. (with
the inward feeling that your thoughts are
racing)? Yes No
5. Are you increasingly distractible—is it

difficult to focus or concentrate when
necessary to do so, or are you easily drawn
away to unimportant or irrelevant things
(as trivial as the sounds of ice dropping in
the icemaker or leaves blowing on the roof)? Yes No
6. Are you experiencing an increased sexual

drive? Yes No
7. Are you overdoing things socially, voca-

tionally, academically, or around the
household—often to a clearly abnormal
degree, for example, studying for much
longer periods of time than necessary? Yes No
8. Are you overactive and restless? Are you

unable to sit still comfortably so that you
need to be constantly up and about? Yes No
9. Are you acting impulsively and over-

optimistically in seeking pleasure and
taking large risks? This is, are you pursuing
what you like without weighing the risks
to yourself—for example, going on
unrestrained buying sprees, initiating
indiscreet sexual relationships, or embarking
on what may be foolish business invest-
ments?* Yes No
If your answer to A is Yes, and if you answer Yes to any four of

these nine questions, you may well be suffering from a manic
illness and should consult a qualified professional. If you have
*Patients who are doing these things often lack insight and may fail
to perceive the risks, which can be clear to anyone who knows the
patient well. This is why it is important to interview the patient’s
spouse or family about her symptoms.
only two or three symptoms, you may have a mild form of

mania (hypomania) and should still seriously consider a checkup.
It is important to emphasize that the manic patient is often un-
aware of these changes in himself, which are obvious to those
around him. The situation is further complicated by the fact
that many manic patients deny that they are experiencing any
problems at all because they feel so good. In cases of manic
illness where the patient is unable or unwilling to acknowl-
edge that he is ill, it becomes particularly important for the fam-
ily to urge him to seek professional help. The consequences of
manic illness, as we will illustrate, can be as self-destructive as
the behavior of the depressed patient.
Like the depressive patient, the patient possibly suffering
from mania should not try to explain his unusual feelings by
life events. Life sometimes goes exceedingly well, and people
can find plausible reasons for believing that their remarkable
happiness is rational. As in depression, in mania what looks
like the cause of the reaction may be the result of the symptoms
of the illness. The feelings of euphoria may be a response to
good experiences but a manic overvaluation of life experiences.
It is easiest to understand the manic patient by thinking of
mania as the flip side of depression. When in a manic state, the
depressed patient no longer lacks interest in life but is trans-
formed into exactly the opposite kind of person. The manic is
interested in everything and is bubbling over with plans. Her
sense of optimism sweeps all doubts aside, and she often im-
pulsively pursues impossible, unrealistic goals.
The depressive’s lack of self-esteem is replaced by a grandi-
ose conviction of tremendous power and superhuman capaci-
ties. The manic patient usually feels on top of the world,
although some are intensely hostile and irritable and engage in
furious squabbles, alienating friends, business associates, and
family. Many divorces occur when one partner has become
manic and the other finds the change intolerable.
The manic seems to be having such a good time that some-
times it is difficult for people to consider him ill, especially when
the illness is a variation of the illness that makes people depressed.
The fact that the manic patient frequently does not believe he is
sick and refuses treatment is particularly unfortunate because

excellent medications, such as lithium, are available for manic-
depression. Therefore, the family members or friends have the
extra burden of talking the patient into treatment.
5 Aaron Archer had been an energetic, prosperous invest-

ment consultant. His partners began to notice that he was
working much longer hours and coming up with many more
ingenious and creative ideas about how to make money. Ini-
tially skeptical about some of Aaron’s ideas, his partners
gradually became convinced that he was an authentic busi-
ness genius. He was sensationally successful at persuading
others of the merits of his schemes. He was his own best sales-
man, showing a dazzling command of facts and figures, and
unshakable confidence. However, his partners were taken
aback when he told them of his plans for a half-billion-dollar
chain of health resorts throughout the United States promot-
ing a secret Russian treatment that would restore youth and
sexual potency to older persons. Aaron produced detailed
demographic projections to support his ideas.
Because of the enormous investment necessary, some of

Aaron’s partners asked for more details about the nature of
the secret miracle treatment. Aaron was outraged by such
questioning of his judgment, and during several very un-
pleasant scenes he uncharacteristically ranted and raved
about their lack of support. Several of his partners gave in,
but one insisted on seeing some proof that this was not some
fly-by-night fad.
The partners were also somewhat disconcerted because the

formerly staid, hard-working Aaron now seemed to have
become a member of the jet set, with frequent flights to and
from Europe in the company of attractive research assistants.
His drinking had also increased substantially.
Financial and personal disaster finally struck when the part-

ners discovered that there was no proof whatsoever of the
usefulness of the new wonder treatment. Big investors re-

fused to join the undertaking, and the company’s large pre-
liminary investment was irretrievably lost. Aaron quit the
company, saying that he was surrounded by fools and as-
sassins. His bewildered wife finally told him that perhaps
he should get some help and received a storm of abuse for
her well-meaning efforts.
Several months later Aaron became depressed. At first he

attributed this to his loss of money, friends, and business.
But eventually he became very inactive and quiet, inter-
ested in nothing and responsive to no one. He was finally
hospitalized.
Treatment
Most of the patients we have described here are victims of bio-

logical depression, although in some of them the symptoms
take the form of physical ailments, unusual behavior change,
or substance abuse. For almost all of them, medication was very
helpful, in some instances producing improvement when other
forms of treatment had not done so previously. For patients
whose depression is less severe or more clearly related to life
circumstances, other treatments—primarily psychotherapy—
or even the passage of time might serve as well. But the point
we are emphasizing in this book is that for people who are in-
capacitated by biological depression treatment with medica-
tion should usually be the first choice. The excerpts that follow
illustrate some of the recovery patterns that can occur with
antidepressant medications.
5 Jill Jason finally became completely inactive. She didn’t

eat, she didn’t sleep, and she didn’t talk. On her doctor’s
advice her husband took her to a psychiatric ward in a gen-
eral hospital. The hospital staff gave her a thorough physi-
cal examination and found nothing wrong except the effects
of malnutrition. Jill thought that she was being punished for
her sins. Her psychiatrist prescribed an antidepressant but

warned her husband that often these drugs take three to four
weeks to work.
During the first week Jill slept somewhat better and began
to eat a little. During the second week she occasionally re-
sponded to her husband’s questions or to comments about
what was happening with the family.
On the seventeenth day of her treatment, when Jill’s hus-

band walked into her room he was astonished to see her
sitting by the bed reading the newspaper. She gave him a
big smile and asked how the children were. Jill’s husband
was flabbergasted. She almost looked like her old self. Jill
said that it was like a curtain had been raised and that for
the first time in months she could really feel and respond.
Over the next week her progress was astounding. She was
the old Jill—laughing, optimistic, and full of plans to fix up
the house. Her doctor warned them that she would have to
continue on the medication for at least six months and that
she would need regular checkups during this period.
5 Mary Malloy’s last boyfriend told her something must be

wrong with her because she was constantly selling herself
short. Further, he could not understand why somebody so
attractive and intelligent wasn’t getting anywhere. Mary had
thought of herself as being attractive and intelligent when she
was a teenager, but lately she had lost faith in herself. Finally,
at the boyfriend’s suggestion, she entered psychotherapy.
However, after many months she hadn’t improved.
Mary’s therapist told her that her new low self-esteem and
performance difficulties were due to fear of success. He sug-
gested that her devoted parents had made an unconscious
bargain with her: they would take care of her if only she
would remain their little girl. Therefore, Mary must learn to
become independent of her parents. When she had achieved
independence, her depression would go away. These ideas

seemed reasonable to Mary, although occasionally she thought
that perhaps she was being dependent on her parents—and
now on her therapist—because she was depressed, rather
than the other way around.
After almost a year of therapy with no signs of change,

Mary’s parents told her that they would no longer pay her
rent if she didn’t switch from a psychotherapist to a psy-
chiatrist. Mary discussed this with her therapist, who pointed
to the possibility that again she might simply be heeding
interfering parents and that perhaps she ought to give the
psychotherapy more time. However, Mary was also getting
somewhat discouraged with the psychotherapy since little
seemed to be happening. She grudgingly agreed to a con-
sultation with a psychiatrist.
The psychiatrist said that she thought Mary was depressed

and would try giving her an antidepressant. She told Mary
that there were several different sorts of antidepressants
available and that if the first didn’t work she shouldn’t get
discouraged. Initially the doctor prescribed the same sort of
antidepressant that had been successful with Jill Jason. How-
ever, the medication gave Mary a dry mouth and constipa-
tion and didn’t seem to help at all. She felt even more
lethargic, and at times her thinking seemed muddled. She
complained about this to the doctor, who told her that these
medications often take four to six weeks to work and that
she should stick with it. The doctor saw Mary regularly dur-
ing the month to try to keep her courage up. However, Mary
simply did not respond; if anything, she felt worse.
Mary’s psychiatrist told her that it was too bad that the drug
didn’t work but that there was another whole group of drugs
that often did work when the first did not. These drugs were
somewhat of a nuisance to use because they required a spe-
cial diet, and if the diet was broken, there was a chance of
unpleasant or even dangerous side effects. This was bad news
for Mary, who had already lost confidence in medication.
Her doctor was sympathetic and reassuring. In explaining

all the pros and cons of the medication, she emphasized how
Mary could benefit from it and pointed out that she couldn’t
continue the way she was.
Reluctantly Mary agreed, went on the diet, and took the new
medicine. Although the doctor said the medicine might take
several weeks to work, Mary began to feel somewhat more
energetic within the first week. By the second week she had
gone shopping and had bought herself some new clothes
for the first time in three years. She also called her old friends.
By the third week Mary told the doctor that she might even
have too much pep and that she was having difficulty sleep-
ing. After the doctor adjusted the dosage of the medication,
Mary soon simply felt good and active again. However, she
had to see the doctor regularly to have her condition moni-
tored and the dosage readjusted as necessary.
After six months Mary was working, had a new boyfriend,

and was developing an interest in cooking. She was often
the life of the party. Mary asked her doctor how long she
had to be on the medication now that she felt perfectly well.
Would she relapse? The doctor said that she couldn’t answer
that question. People with long-standing depressive illness
often had recurrences when they went off medication. The
only way to find out was to try. She said that since Mary had
done so well for six months and her life seemed stable and
rewarding, this seemed a good time to try.
However, Mary also wanted to know whether there would

be any long-term serious side effects if she stayed on the
medication for another six months. The doctor said that there
would be no problem about continuing the medication for
that length of time, and that they could make up their minds
about discontinuing medication later. Mary was concerned
because she was being considered for a promotion and she
didn’t want the possibility of a slump to interfere with her
new career.
Mary’s anxiety and panic attacks had also improved mark-

edly. She was no longer worried that she might have a heart
attack, but she was still anxious about the possible return of
the feelings of panic. She was afraid that if she went off the
medication they might come back.
5 Milton Meyer began to examine every aspect of his life

carefully. He attributed his apathy to a midlife crisis, which
he understood was fairly common among men his age as
they recognized that their adult life was half over. He had
read of existential psychotherapy, which addressed such is-
sues, and after discussing it with a close friend who was a
psychologist, he entered therapy.
In the process of self-examination he began to belittle his work

as a surgeon and minimize his contributions. He viewed him-
self as someone who had been programmed by his family and
background and had lived his life according to their sched-
ule. He saw himself as living out his parents’ wishes for them-
selves in regard to his choice of career, spouse, and lifestyle.
He also began to feel, first from a philosophical standpoint
and later from an emotional one, that life might not be worth
living and that suicide deserved serious consideration—a ra-
tional response to an irrational existence.
At this juncture Milton’s psychotherapist became worried

and referred Milton to a psychiatrist with whom he some-
times worked. Because many of the psychotherapeutic in-
terpretations had made sense to Milton, the psychiatrist had
difficulty in convincing him that a major depression, of bio-
logical origin, might be playing a role in the evolution of his
feelings. The psychiatrist wisely did not challenge Milton’s
intellectual stance, recognizing that he would rather aban-
don psychiatric treatment than give up his painfully acquired
insights. When the psychiatrist queried Milton about his
symptoms, he found many that had been unreported sim-
ply because Milton had not been asked about them by the
psychologist, whose treatment focus had not been on depres-
sion as a possible disease. In addition to Milton’s dispropor-

tionate self-criticism, suicidal thoughts, and a loss of inter-
est in his usual pursuits, he had noticeable sleep problems,
awakening frequently in the middle of the night and early
in the morning, a decreased ability to concentrate, dimin-
ished sexual interest, and a characteristic fluctuation of his
symptoms during the course of the day.
The psychiatrist finally persuaded Milton that medication

might constitute a useful adjunctive treatment to help with
the physiological problems (which Milton believed had come
from his psychological ones) and that he should continue to
work on his psychological ones in therapy. When tricyclic
antidepressants were administered, Milton experienced im-
provement of his depression in the expected sequence. These
first-generation antidepressants were the original antidepres-
sants and are as effective as the “second-generation” or
“new” antidepressants. Newer agents have fewer side ef-
fects, but are probably no more effective; in some patients,
they may be less effective. In Milton’s case, sleep problems
diminished and had disappeared by two weeks, his energy
and concentration slowly improved, by six weeks he was
regaining his interest in surgery, the violin, and gardening,
and in successive weeks he experienced increasing affection
for his family, a return of his sex drive, and a marked lessen-
ing of his philosophical concerns. The psychiatrist suggested
maintaining drug treatment, citing evidence that such de-
pressions have a natural history that must be played out,
and during that time medication usually suppresses symp-
toms. Milton gladly agreed and began to rethink his psycho-
therapeutic experience.
He continued to believe that he had experienced a midlife

crisis and that it had been important for him to re-evaluate
his life goals at that particular time. He also continued to
believe that to some extent his parents’ expectations had pro-
grammed him—as such expectations do for most people—
but over time he considered this less important, recognizing
that the only way not to program a child is to bring him up

without human companionship on a desert island. When his
medication was diminished and discontinued after a year
and a half, Milton re-experienced a recurrent, slight, but iden-
tifiable loss of interest in his customary activities. He was
placed on antidepressants again, and repeated attempts were
made every few months to discontinue them. Five years later
he continued to require maintenance doses of antidepres-
sants in order to avoid recurrence of severe depression.
5 Bob Bush had now been to three gastroenterologists. He

had had X-rays of his stomach and small and large intes-
tines. Nothing had been found. The last doctor stated firmly
that continued tests were going to be a waste of time and
that even if the president had had a colonoscopy that didn’t
mean that Bob should have one.
However, the doctor had just read that antidepressants were

often helpful for people with bowel complaints for which
there didn’t seem to be any physical cause. Bob said that he
would go for anything if the doctor thought it might work.
Bob was started on medication and after several weeks his

abdominal distress disappeared. He no longer felt he had to
check out bathroom locations. His work improved, and he
suddenly found that he was also enjoying life a great deal
more. Looking back, he could see that he had been in a real
slump without knowing it.
5 Peggy Pearl had refused to go to doctors several times,

and her husband was getting fed up with her growing abuse
of alcohol. He finally told her that unless she got help he
was going to leave. Peggy replied that all her troubles were
due to him but he shouldn’t leave.
The Pearls agreed instead to see a marriage counselor. The

counselor listened to their mutual complaints for several
weeks and then told Peggy that he thought she needed some-
thing more than marriage counseling because she was drunk

half the time. During this period her husband’s resolve to
leave unless she got adequate care had been strengthened
by their discussions. Peggy also was becoming increasingly
aware that everything was not her husband’s fault and that
she had an illness that was destroying their lives.
The marriage counselor recommended a psychiatrist to

whom he had often referred patients. When Peggy saw the
psychiatrist, he told her that she was clearly abusing alcohol
but that he thought she was doing this as a result of the se-
vere depression she had experienced before the excessive
alcohol use began. He treated her with an antidepressant,
and after several weeks Peggy’s mood substantially im-
proved and she found herself resorting to alcohol less. How-
ever, her mood was very variable, and she continued to have
bad weeks. The doctor suggested that adding lithium to the
first medication might help. When the combination was tried,
Peggy’s mood became quite stable.
With the improvement in Peggy’s outlook, she and her hus-

band were able to work together again in marriage counsel-
ing. They did have real differences about many aspects of
their life together, but now they could begin to make useful
compromises instead of simply giving up and heading rap-
idly toward divorce.
5 Saul Schwartz refused to take antidepressants. He said

that he wasn’t depressed, that he just had a backache. He
also refused to see a psychiatrist because that was for crazy
people. His doctor and the family talked to him many times
but accomplished nothing. Finally, at the instigation of Saul’s
desperate family, the family doctor took a real risk and told
Saul that he had a new medicine that was good for backs.
Saul was not told that it was actually an antidepressant.
Since Saul was still a free citizen who was in complete charge
of his own life, this was a violation of his civil liberties. Pa-
tients should not be forced or misled into taking medication
against their will. Only if they go through a legal hearing

and are declared incompetent by a court can their decisions
be put aside. In some states even this is not enough and the
courts demand a re-review of all such medication orders even
if the patient has already been found incompetent. Thus, the
paternalistic actions of Saul’s doctor were highly risky. Even
the agreement of Saul’s family that the prescription of a
misidentified medication was necessary would be an inad-
equate defense in a lawsuit.
Saul didn’t like the new medication much because it gave

him a dry mouth and constipation, and he wanted to stop
taking it after a few days. However, his wife carried on so
that he agreed to take the new pills just to have a little peace.
In a few weeks Saul became more active and started talking

about going back to work. He also started to laugh for the
first time in months. When asked if he was feeling better, he
said he felt just the same as he always did, and that his only
problem was his back, which seemed a little less bothersome.
He still didn’t understand why other people had ever called
him depressed. He also didn’t see why his wife kept insist-
ing that he continue his medication.
5 Ralph Rogers’ family was shocked to hear that their son

was a drug abuser. They immediately took him to a psycho-
therapist, whom Ralph saw twice a week regularly for six
months. During this time his grades didn’t improve, and he
was spending more time out late at night with questionable
companions. When his parents complained to his psycho-
therapist, the therapist said that such direct contact between
them and him was interfering with therapy. Ralph had to
understand that the therapist was on his side and not sim-
ply an agent of the parents.
That sounded reasonable, but the situation wasn’t getting any

better. Ralph’s uncle told the parents that he had heard that a
lot of these drug problems could be treated with medicine.
Mr. and Mrs. Rogers reacted negatively to this suggestion.

After all, Ralph’s problem was with drugs in the first place, so
wouldn’t additional drugs just complicate the problem?
After a year Ralph refused to see the psychotherapist any

longer, saying that it was boring and a waste of time. The
therapist said that Ralph had quit because they were getting
close to the source of his difficulties. Ralph’s friends told him
that it was about time that he quit seeing “that shrink” be-
cause all his troubles were due to his parents’ puritanical
attitudes anyway. Ralph’s parents oscillated between trying
to ignore his difficulties, in the vain hope that he would snap
out of it, and erupting into harsh shouting. Ralph continued
to spend large amounts of time out with his friends. It was
unclear how he was getting money for the drugs since he
wasn’t working.
Since at the same time Richard Rogers had quit work in re-
sponse to his own troubles, Mrs. Rogers was in despair at
having two emotional cripples on her hands. She suggested
psychotherapy for her husband, but Richard said that it
hadn’t helped Ralph, so why should he try? However, when
the family physician insisted that medication would help,
Richard started to take antidepressants. Within a month he
was no longer depressed. He slept well, ate well, had a re-
stored interest in sex, and looked forward to getting another
job. He was still desperately worried about his son, but he
wasn’t depressed.
Armed with the knowledge that medication had helped him,

Richard told his son that he would have to move out if he
didn’t go to a psychiatrist for medication. Ralph preferred to
move out, and bummed around for a year. Finally, strung
out and broke, he returned home, His parents insisted that
he have a psychiatric evaluation, and eventually he was
treated with the same medication that had helped his father.
His mood improved in six weeks, and he became interested
in returning to school. He still used a great deal of pot and
associated with semidelinquent buddies. His former bright

future now seemed unlikely. His parents felt that, if they had
caught his depression earlier, his change in lifestyle and the
wasted year might have been avoided.
5 When George Gelb began to participate in the experimen-

tal drug study at the Depression Clinic, the psychiatrist also
met with him half an hour per week for nine weeks, the du-
ration of the study. The first 15 minutes of each session were
occupied by formal questioning and the filling out of forms.
For the second 15 minutes, during which the therapist was
silent most of the time, George would reflect aloud on his
condition. During this nine weeks his sense of sadness and
other symptoms gradually seemed to disappear, and he be-
gan to act in a problem-solving way. After he discussed the
forthcoming separation with his daughter and she elected
to stay with him, he contacted a lawyer. Rather than pas-
sively resigning, he began to contest the divorce. He also
investigated alternative job opportunities.
After nine weeks George was rated as moderately improved,

but he had turned his life around. In the study, however, it
turned out that he had been on placebo. George then accepted
the option of taking the experimental drug. But in four weeks,
before the drug had time to act, he had completely recovered.
George’s story illustrates several characteristics of depres-

sion. First, some patients get better on placebo; second, many
patients get better with the passage of time; third, many pa-
tients get better with the opportunity to talk things out with
a therapist. George had not been receiving formal psycho-
therapy, but he had vented his feelings with the physician,
who was sympathetic even though he made no suggestions
or interpretations and engaged in no other standard psycho-
therapeutic maneuvers. The therapist listened while George
came to terms with himself and began to solve his realistic
problems.
5 When a psychiatrist first saw Carl Carr, he was a down-

cast young man who talked slowly while recounting his
symptoms and brooding about his hand injury. He had lost
interest in everything but his fiancée, and was extremely
anxious, guilty, and preoccupied with thoughts of suicide.
He was close to failing at school, because he could neither
concentrate on nor remember what he was studying. He
had lost 15 pounds, had no energy or sex drive, and al-
though he fell asleep easily, after an hour he awoke and
tossed and turned for the rest of the night. His diagnosis
was biological depression, triggered by life events, which
had persisted for a year and a half and had been unrespon-
sive to psychotherapy.
Carl’s symptoms were classic, the kind that would be pointed

out to medical students as typical of biological depression.
Nevertheless, because the previous therapist had avoided a
medical consultation and antidepressants, Carl may have had
one-and-a-half years of inadequate treatment and unneces-
sary suffering. When the psychiatrist now prescribed one of
the newer antidepressants, Carl responded quickly. Within
two weeks his sleep difficulty was gone, at four weeks his
interest in school returned, and by the tenth week of antide-
pressant therapy he was functioning as well as he had be-
fore the accident. His grades moved from C’s to A’s, and he
and his fiancée moved in together.
The psychiatrist expected that Carl would remain demoral-

ized because of his permanent physical handicap, which
prevented him from doing work he enjoyed very much, but
he took care of his demoralization himself. Without prompt-
ing, he recounted multiple instances in his life when he had
been stymied but by personal efforts had succeeded. One
year later, with minimal psychotherapy, he is functioning
well, and the dose of medication is being reduced to see if
his depression has disappeared. He is planning to get mar-
ried soon and fully enjoys life.
5 Ten years late, Edith Ebel recognized her symptoms in a

research advertisement for depressed subjects. In the study,
she was first treated with an experimental drug, which
worked. As the depressive symptoms responded, Edith be-
came more interested in her job, her house, her golf, and
her sex life. She worried less about trivia and suddenly re-
alized that even her mind was working better—she had not
previously noticed that she had been reading less and get-
ting less out of it. The most surprising feature of her re-
sponse to the antidepressants was the gradual withering
away of her neurotic symptoms. She became less concerned
with one-upmanship, she no longer felt the need to be a
star, she became more gregarious, and her barbed hostility
disappeared.
Edith has now been receiving antidepressants for three years.

When they are gradually lowered or stopped, she does not
suffer a full recurrence of depression but her personality re-
verts to what it was like in her predepression period.
Apparently a chronic mild depression increased Edith’s neu-

rotic response to her disturbing family. An awareness of
the origin of some of her personality traits did not help her,
but medical relief from the depression seems to have al-
lowed her to change and grow in ways she could not be-
fore. In an autobiographical account she describes herself as
now “knowing where I want to direct my life … I am much
kinder now … I no longer rely on degrading peers. I now
like myself and am very secure in who I am … I believe that
this attitude has resulted from my growing in wisdom and
maturity … My family agrees wholeheartedly and enjoys
living with me.”
5 Aaron Archer responded very well to the antidepressants

that were given to him in the hospital. His ability to experi-
ence pleasure returned and he began to show interest in his
former activities. However, he told his wife and doctor that
he had a brilliant idea that would bring back his lost for-
tune. He refused to believe that he had been sick before his

depression and viewed his mania as simply the way he was
when he was normal. Finally, to placate his wife, he accepted
the psychiatrist’s suggestion that he go on lithium. His mood
now shifted to normal. He was able to realize that his grandi-
ose goals were indeed unrealistic and that his feelings of con-
stant exhilaration had themselves been symptoms of an illness.
Mild Forms of Depression and

Manic-Depression (Bipolar Disorder)
Depression and manic-depression are not like illnesses that are

either present or not present. If one has tuberculosis bacteria
growing actively in one’s lungs, one has “pulmonary” (lung)
tuberculosis. Without such bacteria one does not have pulmo-
nary tuberculosis. If an artery in one’s brain is closed by a clot
and the part of the brain nourished by that artery’s blood dies,
one has a stroke. If the artery remains open, one does not have
a stroke. But there are many other diseases that are not “all or
none,” black or white.
This is clearly illustrated in the case of weight. Some insur-
ance company tables may state, for example, that a man of a
particular body build, age, and height should weigh between
165 and 185 pounds. This obviously does not mean that if he
weighs 164 pounds he is skinny or that if he weighs 186 pounds
he is fat. Definite lines have to be drawn for purposes of cat-
egorizing people, but failure to maintain a weight between such
a minimum and maximum does not necessarily reflect the pres-
ence of an underlying disease. Another medically important
example is hypertension. As blood pulses in the arteries, driven
by the heart, the pressure rises to a maximum, called the “sys-
tolic pressure,” and declines to a minimum, called the “dias-
tolic pressure.” For young or middle-aged people systolic blood
pressures over 140 are considered high and diastolic pressures
over 90 are considered high. If one takes these numbers liter-
ally, a patient with a systolic blood pressure of 141 and dias-
tolic pressure of 91 is “hypertensive.” While someone with a
systolic pressure of 139 and a diastolic blood pressure of 89 is
considered to have normal blood pressure. The blood pressures

of the two individuals differ by only 2 points, but one is con-
sidered sick and the other well. Obviously, this is a somewhat
artificial framework.
The same situation exists with respect to depression and
manic-depression. There are mild forms of depression called
dysthymia and mild forms of manic-depression (bipolar disor-
der) called cyclothymic personality.
A psychiatrist does not decide if a depression is biological
simply on the basis of severity. A person may be profoundly
depressed for a while because of the loss of a loved one, and
usually such a depression is psychological. On the other hand,
some people have milder forms of depression that are biologi-
cal in origin. The biological cause is discovered only when the
depression disappears during medical treatment. Many of these
people, who continue to lose interest and pleasure in life, and
experience a decreased effectiveness in accomplishing daily
tasks, frequently have a biological disease. Probably more than
any single symptom, impairment in carrying out the responsi-
bilities of one’s life (as spouse, parent, homemaker, wage earner)
raises the very real possibility of a biological depression.
Dysthymia
Many people have a prolonged, even lifelong form of mild,

chronic depression, which is called “dysthymia.” Below is a self-
rating scale for dysthymia. We emphasize that what makes the
difference between dysthymia and ordinary unhappiness is the
chronicity and persistence of the symptoms. Even successes and
satisfactions alleviate the enduring gloom only temporarily.
Self-Rating Scale for Dysthymia
A. Have you been depressed, sad, down, low,

or blue for most of the day, for more days
than not, for at least two years? (Or have
others perceived you as being this way?) No Yes
B. While depressed do you have any of the

symptoms in the Depression Self-Rating
Scale at the beginning of the chapter? No Yes
C. 1. Do you have feelings of hopelessness

or despair? No Yes
2. Do you have pessimistic thoughts

about the future, do you brood about
past events, or do you feel sorry for
yourself? No Yes
3. Are you increasingly irritable or do

you become angry more readily? No Yes
4. Do you have recurring thoughts of

death or suicide? No Yes
D. Have the past two years gone by without

as much as two months of good feelings? No Yes
If the answers to A and D are Yes, and if you have had any of
the symptoms in B and C, you very possibly have a dysthymic
disorder and should receive an evaluation by a psychiatrist.
Persons exhibiting this kind of depression used to be called
“neurotic,” implying incorrectly that their depression stemmed
from psychological causes and that a cure for their depression
would also have to be psychological, in the sense of psycho-
therapeutic.
A typical case history follows:
5 Harry Hall and Bill Bagley became friends in high school.

Neither was particularly handsome, athletic, popular, or well
liked, but they were not considered offensive and were not
rejected by their classmates. They shared an interest in fix-
ing old automobiles and spent many afternoons tinkering
with an old Ford. In their working-class families money was
always in short supply. Neither boy saw any opportunity to
go to college. After high school they obtained blue-collar jobs

in the same factory, which offered little chance for advance-
ment. Harry complained a great deal about his unreward-
ing life, the lack of social and sexual opportunities, and his
perpetual feelings of fatigue and boredom. Bill shared many
of these complaints, and although he was more outgoing and
energetic, he was also realistically pessimistic and resigned
to his life.
When the United States entered the Vietnam War, their fac-
tory suddenly experienced a huge demand for its products.
Even workers with only moderate experience were given the
opportunity for rapid advancement. Harry saw this as yet
another burden since he did not believe he could improve
his skills sufficiently to rise to a higher level. Bill, on the other
hand, seized the opportunity by going to night school and
by requesting further on-the-job training. He was quickly
promoted and, shortly thereafter, saw his life improve in
another respect when he fell in love with an attractive and
lively girl who reciprocated his feelings.
When Harry’s reliable on-the-job performance was recog-

nized, he too received a substantial promotion, but his gloom
persisted. The more responsible job required him to super-
vise the work of men under him, which he found very diffi-
cult. Harry eventually did find a girlfriend, and once she
knew him better, she pointed out that his gloominess and
lack of pleasure were out of keeping with the realities of his
life. By now he was being paid fairly well, had the opportu-
nity for further advancements, was having a pleasant, if not
exactly passionate, relationship with his girlfriend, and could
pursue his hobbies more easily. Nonetheless, he remained
downcast, tired easily, and was often bored.
A physician’s checkup showed nothing particularly wrong,

but in response to his girlfriend’s urging, Harry told his phy-
sician that he just wasn’t enjoying life the way he should be.
The physician recognized that Harry’s complaints were best
understood as a mild, chronic depression and prescribed a

new antidepressant that had been strongly recommended
as low in side effects and broadly useful. Harry reluctantly
agreed to try the medication. To his surprise, after about a
month his girlfriend pointed out that he seemed more ener-
getic and decisive, and that his habit of chronic complaining
had largely ceased. Harry had not noticed any change.
These gains were maintained for the six months that Harry
stayed on the medication. Then, with his doctor’s approval,
he decided to stop taking it to see what would happen. Life
was going much better and he was feeling pretty good, so
maybe the medicine was by now superfluous.
Unfortunately, after Harry had been off the medication for

three months, his girlfriend noticed that he was losing inter-
est and drive and was starting to complain again.
Bill and Harry had seemed much the same in early life. Both
felt pessimistic—they believed they were unlikely to lead
gratifying lives. However, given an opportunity, Bill was able
to improve his life and experience real happiness. Bill, in
other words, was suffering from chronic but realistic unhap-
piness and was able to overcome it by making good use of
changing circumstances.
Harry, on the other hand, had chronic dysthymia. His ill-

ness was not obvious until his circumstances had improved
enough to reveal the real discrepancy between how he felt
and the realities of his life. Harry’s dysthymia responded to
medication, but as with many chronic illnesses, the medica-
tion did not cure his condition. When he stopped taking the
medicine, the illness manifested itself again. Continuing
medication is necessary for Harry to function at a normal
level.
Might Harry have done well with psychotherapy? Is it pos-

sible that psychotherapy would have so changed him that
his gains would have been permanent? We think not and

will discuss this in detail in our sections on psychotherapy.
Cyclothymia
The milder form of manic-depressive illness, cyclothymia, is

characterized by continual mood swings. The ups and downs
last from weeks to months but never develop into a full-fledged
manic-depressive illness. The answers to the two following criti-
cal questions can indicate whether or not you or someone you
know might be suffering from cyclothymia.
A. Have you had a period of at least two years of fluctuating

mood swings, with highs whose symptoms are listed un-
der our section on mania and lows whose symptoms are
listed under dysthymia?
B. During the two-year period with such mood shifts, have

you been markedly impaired?
If the answer to A is Yes and to B is No, quite probably you

suffer from cyclothymia and should obtain a professional evalu-
ation. Cyclothymia shares one important feature with mania.
During the up periods of cyclothymia, the individual is apt to
think there is nothing wrong with him. He feels terrific, and if
he has not suffered from the consequences of his illness (rash
financial, personal, or vocational moves), he may actively wish
not to have psychiatric help. Nonetheless, if you are a signifi-
cant other in such an individual’s life, and you clearly see these
cyclothymic symptoms, you should as diplomatically as pos-
sible try to get him to professional care.
An illustrative case history follows.
5 Walt Waverley had known since early adolescence that

he would be a writer. He found his greatest pleasure in turn-
ing his acute observations into vivid stories. He kept a diary
and notebooks in which he jotted down odd turns of events
and wry comments. During high school he was the star of
his English class and the Creative Writing Club. At times his
energy was remarkable, and he would spend all night writ-
ing a flood of stories, poems, and essays. He also had a lively
social life, so much so that he was involved in a few drunken
brawls and he was called in by the principal for a dressing
down, a warning, and a period of probation. Walt was also
very popular with girls, who found him vivacious, amus-
ing, and ardent.
In his senior year, Walt slowed down noticeably. The flow of

inspiration and humor dried up so that he spent long hours
at his desk vacantly staring at a piece of paper. He began to
eat and sleep more. Although he would respond to his par-
tying friends, he was not the same old Walt. His school work
suffered, and his friends told him that he was becoming a
hermit. He said that the last year of high school was a drag.
However, after a dull summer, when he entered college in

the fall he went back to writing with his old flair and energy.
Once again he was successful, ebullient, and witty. He didn’t
understand what had happened to him over the past sev-
eral months but attributed his returned energy to the stimu-
lation of college.
Unfortunately, these periods of mood alteration became a

routine part of his life. For several months he would be ener-
getic and productive, and then for several weeks to several
months his energy would flag, he slept and ate more, and he
lacked his creative spark. He was never severely incapaci-
tated during his depressed periods, but he tended to be apa-
thetic and could not be productive. During his up periods,
he was strikingly creative, although at times his rush of
thought was so great that his output lacked clear structure.
He also tended to drink and party too much.
Walt began to refer to his down periods as “writer’s block.”

He began to see a psychotherapist, who attempted to get
him to see his unproductive periods as the result of fear of
success and as ways of punishing himself. Although eager

to believe anything that would explain his inexplicable os-
cillations, Walt found the treatment ineffective. His thera-
pist admitted that perhaps they weren’t making much
progress, and if Walt wished, he would be referred to a psy-
chiatrist that he collaborated with on difficult cases. After
much discussion, Walt eventually tried lithium. However,
Walt was paying for both the psychotherapist and the psy-
chiatrist and, therefore, limited the frequency of his psychi-
atric visits. When he developed side effects such as dry
mouth, tremor, and frequent urination, the psychiatrist sug-
gested that Walt be seen more often, so that dosage adjust-
ment and blood-level monitoring could be carried out more
effectively. The psychiatrist felt that it would require fairly
close attention to find a dosage level that would even out
Walt’s mood without causing unpleasant side effects.
At this point, Walt discontinued the medication because he

was afraid of it, felt that he could not afford closer monitor-
ing, and feared that the lithium might interfere with his cre-
ativity. His psychotherapist supported him in this decision,
saying that he was glad that Walt was mature enough not to
look for a magical pill. Walt never took lithium long enough
to find out whether it would work or if it would cause the
feared decrease in productivity.
Although Walt’s work was beginning to receive some recog-

nition, editors found it difficult to develop a working rela-
tionship with him because his output was so erratic. His
unpredictability was often blamed on his drinking, although
interestingly his drinking occurred primarily when he was
up rather than down.
People with cyclothymia often do not realize how their

swinging moods dominate their life. They find external rea-
sons for both the good and the bad periods. Most cyclothymic
people never enter treatment, so this is not a well-studied group.
We do know that at times cyclothymic mood disorder will turn
into a full-blown manic-depressive disorder. We know this be-

cause, when careful histories are taken of manic-depressive
persons concerning their life before the severe illness occurred,
it often becomes plain that they had undergone a clear series of
moderate ups and downs for many years that had gone unno-
ticed and untreated.
The Interpersonal Consequences of

Depression and Manic-Depression
Depression and manic-depression affect not only the individual

sufferer but all the people with whom he or she is involved—
friends, relatives, employers. Some of the consequences of de-
pression are relatively straightforward and easy to understand:
to the spouse of the depressed individual, he or she is often a
wet blanket. The depressive mopes, is uninterested in social
activities or hobbies, is indecisive, derives little pleasure from
anything, and is frequently irritable and angry. Well-intentioned
suggestions that the depressed person should “buck up” or
“snap out of it” not only are unsuccessful but are likely to pro-
voke further annoyance and anger. Persistent recurrent depres-
sion can obviously be very hard on relationships.
Life with the manic-depressive individual can be intolerable
in different ways. Excessive high spirits during euphoric ma-
nia, unwarranted by the circumstances of the couple’s lives,
are usually upsetting to the unaffected partner, who realizes
that real-life problems and difficulties are being minimized,
underestimated, and viewed through rose-colored glasses. If
the mania takes the form of marked irritability, the relationship
can begin to fall apart. The manic’s impulsivity may also gen-
erate fear and anger. Spending sprees or poorly considered
business initiatives may threaten the family finances or even
bankrupt them. The increased sexual drive may disturb the
partner, but what is far more likely to be disturbing and mas-
sively destructive is the manic’s tendency to initiate casual
sexual liaisons.
A spouse’s depression can be withstood out of guilt and con-
cern. However, the manic seems reprehensible because he is
breaking the social contract while apparently having a won-

derful time. Divorce frequently ensues.
With these examples of the kinds of problems that depressed
and manic people can have, and of the good responses that
many such patients have to medication, we hope we have con-
veyed some sense of the nature of these mood disorders. In the
rest of the book we will go into more detail about the course of
depression and manic-depression, theories about the causes of
mood disorders, diagnosis and treatment, related disorders, and
ways to get help. In particular, we will discuss the eventual
outcome of Mary Malloy, Jill Jason, and Jane Harris to illustrate
the wide range of possible outcomes.
3
What Happens to the
Depressive or
Manic-Depressive
Individual Over Time?
BEFORE DISCUSSING the course of depression and

manic-depression (bipolar disorder), we want to comment on
the frequency of these illnesses. For reasons that are incom-
pletely understood, depression has become increasingly com-
mon in recent times. That is, the rates of depression were lower
for people born in 1900 than for those born in 1920, and lower
for the 1920 group than for those born in 1940.
Recent figures are largely derived from a survey known as
the Epidemiologic Catchment Area Program. This program used
a specific interview to gather the data but did not use trained
clinicians. Therefore, the figures can be considered only approxi-
mate. Almost 30 percent of the population reported a period
lasting at least two weeks when they felt sad or blue. However,
about 5 percent of the population reported a major severe de-
pression during their lifetime. Dysthymia occurred in about 3
69
percent of the population, and another 3 percent of the popula-

tion reported manic symptoms in the form of one-week periods
or more of elevated, expansive, or irritable mood. Roughly 1.5
percent had a diagnosis of bipolar (manic-depressive) disorder.
In any given year, 4 or 5 percent of adults became depressed.
(The study did not evaluate people under the age of 18.) There-
fore, roughly 10 to 12 million Americans become depressed each
year, although not for the first time, and about 2 million have
manic-depressive episodes each year. More recent epidemiologi-
cal studies suggest that the numbers are even larger.
Depression is twice as common in women as in men, while
manic-depression is equally common in both sexes. Although
the reasons for this distribution are unknown, one popular
theory is that women are more likely to suffer from depression
than men because their lives are more oppressive. But is the
rate of depression higher among groups of people who are dis-
advantaged, deprived, the targets of prejudice, or some combi-
nation of these factors? One such group is African Americans.
When the rate of depression in this group was measured, the
findings were unexpected. In blacks between the ages of 30 and
64, the rate of depression is slightly lower than it is in whites.
This suggests that the relationship between social oppression
and deprivation and depressive illness is not a clear-cut one.
Attempting to explain the increased depression rate in women
as due to “stress” also falters. If stress causes women to be de-
pressed, and if stress shortens lives, why is it that women live
significantly longer than men? The point is that it is easy to
come up with psychological explanations when the real causes
may be biological. We agree that discrimination and oppres-
sion are harmful, but this is very different from saying they
cause severe mental illness. Despite the plausibility of such an
explanation, it does not agree with the facts.
The gender distribution of severe depression may in fact be
changing. For the past 45 years psychiatrists in Sweden have
been studying a large semirural community, interviewing all
of its members at fixed intervals to determine whether they
have developed or are suffering from psychiatric illnesses.
During the course of this study, the frequency of depression in
young men has gone up tenfold.
The Depressive or Manic-Depressive Over Time 71
Depression in young children and adolescents also may have

increased. Up until the past ten years, psychiatrists believed
that depression was relatively rare in adolescents and children.
However, with growing evidence that some forms of depres-
sion are inherited, psychiatric researchers have begun to study
the children of parents with these disorders, and they have
found that symptoms of depression—usually but not always
mild—can be identified in such children. Frequently, the de-
pressions in children have not been recognized by the parents
and are found only when the children are interviewed. Sys-
tematic studies on depression in children are now under way.
The Symptoms of Depression in

Children and Adolescents
Although the major symptoms of depression in children include

many of those seen in adults, other symptoms seem more spe-
cific to childhood—such as poor relations with parents, siblings,
and school mates, irritability, and “insatiability.” Many parents
report that it is impossible to make these depressed children
happy. This insatiability of depressed children corresponds to
the loss of interest in life and the inability to enjoy oneself ex-
perienced by adult depressives. Depressed preadolescents,
unlike many younger children, can report some subjective
symptoms of depression—experiences of sadness, thoughts of
death or suicide, and disturbances of sleep. Parental informa-
tion on preadolescents is still useful, however, because parents
are quicker to perceive symptoms that the child may fail to rec-
ognize, such as poor social functioning, irritable mood, and lack
of interest in normal childhood activities.
Depressive disorder tends to develop slowly in younger chil-
dren, but it is more likely to be relatively sudden in adolescents.
In adolescents, the disease shares more of the symptoms of adult
depressive disorder, such as feelings of inadequacy. The picture
is complicated by the tendency of depressed youngsters to de-
velop behavioral problems that involve rule violation or delin-
quent activities and to abuse alcohol and drugs. It is possible
that in turning to such substances, depressed adolescents are

unwittingly groping for “over-the-counter” antidepressants. We
want to emphasize this because the substance-abuse problem
may be the squeaky wheel that gets the psychiatric attention,
while the accompanying mood disorder is being overlooked.
Adolescent depression is also very changeable and may alter-
nate with excited, exuberant periods.
A number of other childhood psychiatric disorders overlap
with and may look similar to biological depression. If a child
has symptoms suggestive of depression, he should receive a
full evaluation from a child or adolescent psychiatrist.
In identifying depression in children and adolescents, it is
important to know that, if depressive or manic-depressive dis-
order is present in one or both parents, the odds that the child
will develop such an illness are considerably increased. Thus,
if a parent(s) has mood disorders and her child or adolescent
develops psychological problems of any kind, an evaluation is
even more necessary than usual. Such early psychological prob-
lems may forecast a mood disorder, even though all of the symp-
toms may not appear at once.
Parents are unlikely to obtain psychiatric evaluations for their
children for several reasons:
1. As noted, until recently, depression and manic-depression

were thought to be exceedingly rare in preadolescent chil-
dren. Similarly, it had long been believed that bipolar dis-
order did not occur in children. But recently, it has been
claimed that many children with attention-deficit hyperac-
tivity disorder actually suffer from bipolar disorder. Yet
many of these children have chronic rather than periodic
illnesses (bipolar disorder is characterized by periodic ill-
ness in adults) and there is no evidence that these children
respond to antimanic drugs. There may be something seri-
ously wrong in many of these children, but whether it is
bipolar disorder is questionable.
2. Parents can seem to find reasons to “explain” their child’s
psychological or behavioral changes. Since all of us have
experienced repeated frustrations and disappointments that
can provide us with “reasons” that seem to explain our own
erratic moods, we apply these “reasons” to our children as

well. However, we should be suspicious of our logic. Were
someone, unbeknownst to you, to place a drug in your
morning coffee that made you profoundly depressed, you
would undoubtedly be able to find current and past life
experiences that would seem to adequately explain your
depression.
3. Parents are often unaware of the feelings of their children.
In one study of children of depressed parents, one-third of
the children were found to be depressed, a situation unrec-
ognized by their parents.
Warning Signals for Parents
During preadolescence the hallmarks of depression are:
1. Inexplicable decrease in academic performance.

2. Increasing social isolation.
3. Loss of interest in sports.
4. Development of unusual physical complaints for no medi-
cally sound reason.
5. Increased childish and dependent behavior.
6. Excessive demandingness.
A childhood disturbance that closely resembles depression

and that may turn into a depression in later life is extreme so-
cial anxiety. Such children are extremely shy, avoid social gath-
erings, become extremely anxious when called upon to perform
in public, as in giving a report in class, fear authority, and can-
not initiate social interactions.
In adolescence, the symptomatology of depression changes.
However, since adolescence has gotten a bad reputation, par-
ents are not always aware of what might be early warning signs
of depression. For example, it is commonly believed that it is
normal for an adolescent to go through extreme moodiness,
outbursts of temper, and delinquent behavior. This is simply
not true. Most adolescents living under reasonable and
nondepriving circumstances do quite well. Therefore, one
should suspect depression if one observes the following:
1. Marked moodiness.
2. Overreactions to frustrations out of all proportion to the
provocation.
3. Marked self-isolation and social withdrawal.
4. Unrealistically low self-esteem.
5. Unwarranted belief that others dislike or reject him or her.
6. Unrealistic belief that one’s personal appearance is ugly or
offensive.
7. Loss of interest in hobbies, sports, and personal self-care.
8. Development of delinquent activities, in particular the
abuse of drugs and alcohol.
One of the great problems in evaluating adolescents is that

many teenagers use illegal drugs and alcohol. Thus, it is often
not clear whether their use of these substances has induced a
depression and then disrupted their lives, or whether the de-
pression has caused the illegal drug use to begin with. Frequently,
the only way to determine the cause of drug or alcohol abuse is
to hospitalize the patient away from drugs and alcohol and
monitor him for a period of abstinence. Unfortunately, such
lengthy diagnostic hospitalizations are no longer possible with
managed-care restrictions. If the drug abuse was due to depres-
sion, one would expect that the depression would persist or even
get worse, whereas if the drug abuse or alcohol caused the de-
pression, then one would expect that this would be alleviated
by abstinence.
If you observe any of the behaviors discussed here, seek the
advice of a child psychiatrist.
The “Natural History” of

A medical description of the course or “natural history” of an

illness is a description of its possible outcomes: how long it
lasts, what proportion of patients get better or worse, and how
quickly patients recover without treatment. The natural history
of depression follows several common patterns, and in most of
them the symptoms will likely return from time to time. How-
ever, these recurrent symptoms can usually be controlled. In

the rest of this chapter, we discuss several courses of depres-
sive illness and of manic-depression that we have observed in
our patients.
Patterns of Depressive Illness
If we were to come up with a typical pattern for depression, it

would look something like this:
Well → Depressive illness → Well
In this form a person is going along without any life problems—

minding her own business, so to speak. Then, either in reaction to
life difficulties or for no apparent reason, she becomes depressed.
These depressions usually last from about six months to two
years. The number of such depressive episodes that a person
can experience varies tremendously. Some people have only
one attack of depressive illness, some people have several, and
an unfortunate few suffer many attacks. The intervals between
attacks also vary considerably. Sometimes episodes occur in
bunches and do not recur for many years, while in other in-
stances depressive episodes occur at widely spaced intervals.
5 Jane Harris was treated with Prozac, but showed little

effect from it for approximately four weeks. Between four
and six weeks, however, she started to develop her old in-
terests, became energetic, and widened her social activities.
Within ten weeks, she had returned to her former energetic,
rewarding life. Her doctor warned her that she would re-
quire at least six months of treatment since there was a good
chance of relapse if the treatment was stopped too soon. Af-
ter six months, Jane did stop the medication and maintained
her gains completely. She checked in with her doctor every
few months over the ensuing year, and after that, they talked
yearly. Jane and her doctor hope that there will never be a
recurrence of her illness and they may be right, but there is
no way to be sure.
Another pattern may look something like this:
Well → Depressive illness → Treatment →

Well → Treatment discontinuation →
Mild chronic depression
In this pattern a person who develops a depressive illness is

treated with medication, after several weeks or months, the
patient feels better, and the medication is diminished and then
stopped. The person no longer experiences the symptoms of
intense depressive illness, which was treated, but he or she does
not feel up to par. For example, the patient’s interest in his usual
activities may not have completely returned, and he may still
be rather passive, with decreased self-esteem and decreased
energy. These are the symptoms of a new and persisting mild
depressive illness.
These mild symptoms can be eliminated by the same medi-
cation that treated the severe depressive illness, but their con-
trol requires the continuing administration of the medication.
In other words, the patient must continue to receive antide-
pressant medication regularly if he or she is not to suffer a re-
lapse into the symptoms of mild depressive illness.
5 Mary Malloy, after a year of feeling well, was tired of stay-

ing on the diet her medication required. Her doctor told her
that he was not sure what would happen when she went off
medication but that he would follow her closely and they
would see. After the medication was discontinued, Mary
experienced two good months. She felt fine, her old self, and
continued her outgoing pattern.
Slowly, insidiously, she began to sleep more and more. She

found that on weekends she could sleep the day away and
that it was progressively more difficult to get up for work.
Because her weekends became disorganized, she found her-
self snacking on potato chips all day, often washed down
with a beer or two or three. Her weight began to go up. Her
relationship with her boyfriend became somewhat rocky
when she started to complain that he was ignoring her, al-
though in fact his behavior was no different than usual. Fi-

nally, she and her doctor agreed that things were not going
well since the medication was stopped and that she was hav-
ing a relapse. With the resumption of medication, the disease’s
process was interrupted, and within six weeks, Mary was
back to normal.
She and her doctor discussed this in some detail. She pointed
out to Mary that it was unfortunate that she had a chronic
illness, but that she really had to look upon herself in exactly
the same fashion as somebody with hypothyroidism who
has to take thyroid supplements for the rest of his life, or
somebody with diabetes who must take insulin to stay in
balance. Nobody likes to be ill, but if you are ill, it’s reassur-
ing to know that there is a medication that effectively brings
you back to normal. Furthermore, these medications do not
lose effectiveness over time. In a year or so, they might try
going off the medication again, although they shouldn’t be
overly optimistic about the outcome of this. Nonetheless,
some depressive illnesses do seem to burn out with age and
perhaps eventually Mary would not need medication.
5 Jill Jason’s story was somewhat different. She too had

done extremely well on medication, continued on it for six
months, went back to work, and maintained her gains for
three years. Then, abruptly, and for no apparent reason, her
depression returned with full force. However, by then, Jill’s
husband knew the picture and forced her to go for treatment
immediately, to which she once again responded.
Since this was her second episode of severe depression, her

doctor discussed with Jill and her husband the possibility
that she should receive a prophylactic medication—that is,
that she should not go off medication at all but take medica-
tion daily in the hope that this would prevent recurrences.
Jill adamantly opposed this. After all, she had had several
very good years and was there any assurance that her dis-
ease would recur? Therefore, once again after six months,
the medication was discontinued. Jill went along perfectly

well for five years, when she had another recurrence, which
again responded to the hastily instituted treatment.
Jill’s doctor was firmer this time, saying “Three episodes of

severe depression is really too much. The odds that you are
going to have another are high.” Jill and her husband were
left puzzled. The doctor assured them that there were sev-
eral different medications that might be used for the preven-
tion of recurrence and that they were safe, effective, and had
little in the way of side effects, although they did require
monitoring. What Jill and her husband had to balance was
taking medication indefinitely versus the likelihood of re-
peated and marked life disruptions.
One important psychological factor was Jill’s reluctance to

be considered ill. Taking medication every day reminded her
every day of her illness, and this upset her. Her doctor coun-
seled the family over some time. Finally, Jill’s husband told
her that he couldn’t see her go through another one of these
episodes—for her sake, not just for his. At this point, Jill re-
luctantly agreed to take lithium. Even though she was not a
manic-depressive but had recurrent unipolar depression,
lithium was an effective treatment in the prevention of re-
current unipolar depression.
After two years on lithium, Jill complained to her husband

that she felt that she was running out of gas. She did not
have the severe insomnia, loss of appetite, and social with-
drawal that she had previously, but nonetheless, there was a
clear problem. Jill’s doctor gave her an antidepressant in
addition to the lithium, and she quickly returned to normal.
It seems that, for many people, lithium may not entirely block
depressive recurrences, but it does modify their severity so
that the depression is not as painful and incapacitating and
is more easily treated. Without lithium, Jill would undoubt-
edly have had yet another severe depression at this point.
A third pattern we have observed is the following:

Mild, chronic depression → Depressive illness →

Treatment → Well → Treatment
Discontinuation → Mild, chronic depression
In this pattern the patient has been mildly and chronically de-
pressed from adolescence or even childhood, develops a de-
pressive illness that is treated, and experiences a newfound
feeling of well-being. When his medication is discontinued, he
then returns to a state of mild depression. Interestingly, before
they have the depressive illness, many of these patients do not
know they had always suffered from depression. But when they
develop depressive illness and are successfully treated with
medication, they feel better than they have ever felt in their
life. This is not because medication has made them high or
manic. It is simply that when the symptoms are removed, pa-
tients notice the difference. Such patients are similar to a child
with a vision defect who begins to wear glasses that success-
fully compensate for the defect. When such a child realizes that
he now has no difficulty in figuring out what is on the black-
board, he begins to see himself differently. To be exact, we can-
not say that depressed patients of this kind have been depressed
since birth, but we can often say that they have been depressed
as far back as they can remember; in many instances, this may
be as early as five or six years of age.
One final pattern may look like this:
Well → Mild depression → Well → Mild depression → . . .
Not only severe depressive illness but also mild depression can
occur in episodes. When mild depressions appear and disap-
pear on an irregular basis, they are often not noticed or are mis-
taken for psychological depressions. We would like to
reemphasize the point we made in chapter 2 that it is not sever-
ity that distinguishes a biological depressive illness from a
nonbiological depression but the pattern of symptoms. The same
persons who can experience severe episodes of depressive ill-
ness may at other times experience similar but less intense epi-
sodes of depression. Recognition of the nature of these illnesses
is important because they frequently respond to medication and
may not respond to psychotherapy. Certainly, if major depres-

sion is followed by a “minor depression” or dysthymia (chronic,
mild depression), and psychotherapy has not been effective
within three months, medication should be considered.
Patterns of Chronic Depression
Twenty or thirty years ago it was believed that when an epi-

sode of depression resolved the patient’s mood returned to
normal. This is frequently not the case. Current estimates are
that approximately 20 to 25 percent of persons who suffer a
biological depression will develop a mild, chronic depression,
which in turn may be punctuated by episodes of severe de-
pression. It is increasingly obvious that many such patients must
remain on antidepressants permanently or semipermanently.
They are like patients with pernicious anemia, whose symp-
toms can be relieved by the administration of vitamin B12 but
who must stay on that vitamin in order to prevent the recur-
rence of pernicious anemia. Another analogy is that of epilepsy
(which bears no relationship to depression). Many epileptics
suffer seizures at infrequent intervals—for example, three or
four times a year—but take an anticonvulsant on a continuing
basis. A similar situation seems to hold for many depressives.
As researchers in psychopharmacology have been able to fol-
low their patients for longer periods of time, they have begun
to recognize that chronic depression may be even more com-
mon than previously believed and may require indefinite anti-
depressant therapy.
Patterns of Bipolar Disorder
The course of bipolar disorder can be much more variable than

the course of unipolar depressive illness, because any new epi-
sode can be either “up” (the manic phase of the illness) or “down”
(the depressive phase). In addition, both “up” and “down” epi-
sodes can be either mild or severe. In other words, a manic-
depressive patient may be manic, hypomanic (manic without
impairment), mildly depressed, or severely depressed. An ad-
ditional complication is that the onset of manic-depressive ill-
ness is unpredictable. The following two patterns illustrate how

manic-depression can vary:
Well → Depression → Mild depression → Well →

Depression → Mild depression → Manic → . . .
In this pattern an individual may experience several episodes

of depression—separated by either complete recovery or mild
depression—suffer several such bouts, and only much later
have a manic episode. In effect, the patient has been manic-
depressive, but the diagnosis could not be made until the first
appearance of mania.
Here is another pattern of manic-depressive illness:
Normal → Mania → Normal → Depression → Normal →

Depression → Normal → Depression → . . .
In this course a manic episode is followed by a return to nor-

mality, followed by recurrent depressive episodes with inter-
vening periods of normality.
How often new episodes occur varies a great deal, from only
one attack of manic illness in a lifetime to several per year. The
major medications used in the treatment of manic-depression,
lithium and certain anticonvulsants, can prevent attacks of
mania or depression, or they can diminish the severity of at-
tacks; when given for a long time, they may prevent attacks
altogether. Studies have found that the average person with
manic-depressive disorder loses about nine years from his or
her life. That is, the person is unable to function as a student,
homemaker, or worker for a total of nine years (usually spread
out over a number of episodes). Without treatment, the average
person with manic-depressive illness is out of commission for
9 of the 49 years between the ages of 21 and 70, or for about 18
percent of his or her adult life.
Patterns of Mild Manic-Depression
Some people have a manic-depressive illness in which they

experience only mild forms of both symptom extremes. When
they alternate in a fairly rhythmic and continuing way, they are

diagnosed as “cyclothymic personality.” Their “up” periods
never exceed hypomania, so they do not become grossly im-
paired or require hospitalization. These ups and downs may
follow each other without interruption, or they may be sepa-
rated by normal intervals that can last for months. Such people
are often referred to as “moody.” Once one knows what to look
for, the regular alternation of mood in this disorder makes it
fairly easy to recognize. An occasional fortunate person is per-
sistently hypomanic for much of his life without swings into
depression. Such people are generally considered impressive,
productive, creative people, and it is only the appearance of
depression that makes it evident that their high productivity
was to some degree the result of their disease-incited high level
of drive.
4
What Causes Depression
and Manic-Depression?
THE MAJORITY of cases of depressive and manic-

depressive illness appear to be genetically transmitted and chemi-
cally produced. Stated differently, the disorders seem to be
hereditary, and what is inherited is a tendency toward abnor-
mal chemical functioning (sometimes called a “chemical im-
balance”) in the brain. Antidepressant medications apparently
have a compensating effect, correcting the imbalances that are
believed to cause depressive and manic-depressive illness.
Hereditary Factors: Patterns of Depressive

and Manic-Depressive Illness in Families
Depression and manic-depressive illness—mood disorders—

run in families. In the course of their lives, the brothers, sisters,
parents, and children of a depressed person have a risk of ap-
proximately 20 to 25 percent of having the disease themselves.
This contrasts sharply with the brothers and sisters, parents
and children of a nondepressed person, 5 to 6 percent of whom
83
may have the disorder. Although depressive and manic-depres-

sive illnesses do occur more frequently in particular families
than in the population at large, they do not always appear in
the families we would predict they would and sometimes can
skip generations. A grandparent may have one of the disor-
ders, but his or her children may escape the disease or may
have related problems with alcohol. Subsequently, the grand-
children may show symptoms of the illness. The type of de-
pressive illness can also vary from one generation to another. It
is not uncommon for a parent to be manic-depressive and for
the child to have a depressive illness without the manic aspect.
Finally, heredity does not seem to be an all-or-none matter. As
we have discussed, depression and manic-depression occur in
severe forms and in milder forms, such as dysthymia or cy-
clothymia. Close relatives of the depressive or manic-depres-
sive may inherit either the severe forms or the mild forms of
these mood disorders.
Heredity Versus Environment
The tendency of mood disorders of this kind to run in families

has been recognized for hundreds of years. Certainly, the de-
gree to which mood disorders occur in both parents and chil-
dren does not tell us whether nature or nurture is more
important. Are parents transmitting the illnesses to their chil-
dren through their genes or by the environment in which they
raise them? Might not being raised by a chronically depressed
parent—one who took no joy in life or joy in his child’s accom-
plishments, who because of self-preoccupation failed to praise
his child and emotionally neglected him—produce depression
in his child or even suicide? Suicide, which we discuss pres-
ently, also runs in families. But might not the willingness to kill
oneself be learned? In certain cultures, such as that of Rome
2,000 years ago or of Japan as late as World War II, committing
suicide was a socially approved way of avoiding a more hor-
rible death, reclaiming one’s besmirched honor, or sacrificing
oneself for society’s greater good. So the fact that suicide runs
in families might simply be the result of a family member’s
What Causes Depression and Manic-Depression? 85
experience with it. It is important to emphasize strongly that

the degree to which depressive illness and manic-depressive
illness occur in both parents and children does not tell us
whether nature or nurture is more important. Some learned
traits run overpoweringly in families—for example, with few
exceptions the children of English-speaking parents speak En-
glish and the children of Russian-speaking parents speak Rus-
sian. On the other hand, some genetic traits appear in families
inconsistently—for example, not all of the children of redheaded
parents have red hair. Whether mood disorders are caused by
heredity or environment—by nature or nurture—is of extreme
importance.
Over the years geneticists studying psychiatric illnesses have
tried to devise strategies to determine the extent to which de-
pression may be inherited. One of the first methods used to
tease apart the complex relationship between nature and nur-
ture was the study of identical (monozygotic) and fraternal
(dizygotic) twins. Identical twins arise from only one fertilized
egg, which at an early stage in embryonic development splits
in two. Fraternal twins arise from the fertilization of two differ-
ent eggs. Identical twins (or identical triplets or quadruplets)
are the only instances in which two individuals have exactly
the same genes. The genes are the chemically coded instruc-
tions that oversee the development of the fetus and that mi-
raculously enable a tiny fertilized egg to develop into the
immense complexity of the human body and brain. Not only
are identical twins very similar physically, but they are very
similar mentally. For example, identical twins who have been
adopted by different families in early childhood grow up with
intelligence levels that differ from each other only slightly less
than those for identical twins raised together. Fraternal twins
are no more similar in intelligence than any other brothers or
sisters in the same family.
Aware of such differences in the two kinds of twins, psychi-
atric geneticists decided to study psychiatric illnesses in iden-
tical and fraternal sets. The theory was very simply, if genetic
factors played a crucial role in the development of psychiatric
illness, then if one identical twin had the illness, his “co-twin”
should have exactly the same illness. On the other hand, if a
fraternal twin had such an illness, one could expect the co-twin
to have the illness only about 10 percent of the time—the same
rate as that for other brothers and sisters who were not twins.
Identical and fraternal twins with psychiatric illness were ob-
served in many settings, and it was repeatedly found that in
about 33 to 70 percent of instances identical twins were “con-
cordant” for psychiatric illness. That is, if one identical twin
had a biological depression or a manic-depressive illness, then
in about 33 to 70 percent of the cases the co-twin would have
the disorder as well. The fraternal concordance rate was about
20 percent—slightly larger than anticipated.
Psychiatric researchers who believe that environment plays
a large role reacted to these findings in two ways. First, they
pointed out that many identical twins are raised in a special
way: parents are likely to give them “cute” similar names (Bar-
bara and Betty, Jane and June), dress them in identical clothes,
and raise them so that they develop a closeness not seen in other
siblings. Perhaps, it was reasoned, this accounted for the higher
concordance rate in identical twins compared to fraternal twins.
Furthermore, these theorists argued, if in 33 percent of “identi-
cal” twin pairs only one twin had the illness, then environmen-
tal factors—the psychological environment—must be playing
a role. However, a study of identical twins raised apart in dif-
ferent families found that 8 of 12 sets or 67 percent were concor-
dant. This is a percentage very similar to that of identical twins
reared together and implies that similar upbringing is not the
reason identical twins are concordant. In summary, this re-
search strongly suggests that depression and manic-depression
are genetic. However, the research cannot explain why “identi-
cal twins” are not really identical—completely concordant—
100 percent of the time.
It is useful here to compare this twin research with twin re-
search on nonpsychiatric diseases. For example, the clearly bio-
logical disease of juvenile diabetes (diabetes in people under
30) has a concordance rate of only about 15 percent in identical
twins. Club foot is an abnormality that involves genetic factors
but is concordant in only 23 percent of identical twins (and much
less, about 3 percent, in fraternal). In other words, for both psy-
chiatric and nonpsychiatric illnesses, concordance rates in iden-
tical twins are variable. Identical genes do not always result in

identical diseases. Depressive and manic-depressive illness,
however, do appear to be more genetic in origin than some other
nonpsychiatric biological illnesses.
The twin research thus implicated genetic factors but left the
problem of the relative importance of heredity and environ-
ment unsolved. Identical twins of depressed parents might be
depressed partially for genetic reasons and partially because of
the psychological tendencies of twins to learn similar tastes,
values, and ways of dealing with people and the world.
In the early 1960s, investigators took another step forward
in distinguishing between the effects of nature and nurture
when they hit upon the straightforward and simple technique
of studying adopted persons. In adoptees one set of parents
supplies the genes while the other supplies the environment. If
it is true that psychiatric illness can be psychologically “caught”
from a psychologically disturbed parent, early removal from
that parent should prevent the later development of the disor-
der. But if the disorder is genetically passed from birth parents
to child, the adopted child has just as great a risk of developing
the illness in question as she would if she had not been removed
from her biological parents. The adoption strategy has been
applied to the study of several psychiatric illnesses, including
depressive illness and manic-depression.
The adoption study of depression and manic-depression
began by identifying one group of adults adopted in infancy
who were now depressive or manic-depressive, and a compari-
son group of adoptees of the same age and sex who did not
have depression or manic-depression. The investigators then
evaluated the biological parents and siblings of both groups—
whom the adoptees had never met—and the adopting parents who
had raised them and the adopted siblings with whom they had
been raised. If genetic factors play a role in the transmission of
depression and manic-depression, then one would expect to see
an increased frequency of depression and manic-depression in
the biological parents and siblings of the adopted depressives in
comparison to the biological relatives of the normal adoptees.
On the other hand, if depression and manic-depression are trans-
mitted by life experience and experience within the family, then
one would expect to see a greater frequency of mood disor-

ders in the adopting parents of the depressives and manic-
depressives.
What was found? There was a greater frequency of mood
disorders only among the biological parents and siblings of the
adopted manic-depressives. This showed that genetic factors
were playing a role. The other finding was that frequency of
mood disorder among the adopting parents of the ill adoptees
was not greater than that among the adopting parents of the
psychologically healthy adoptees. In other words, no evidence
was found that rearing played a role in the development of de-
pression and manic-depression.
This study also had one unexpected and dramatic finding:
the biological relatives of the mood-disordered adoptees were
15 times as likely to commit suicide as the relatives of the nor-
mal adoptees. How is this to be explained? It is highly unlikely
that genes transmit a tendency to kill oneself. What is likely is
that a mood disorder in these biological relatives resulted in
their suicide (remember that from 10 to 30 percent of depressives
and manic-depressives kill themselves). The same finding of
genetic contributions to suicide was duplicated in a study in
which investigators examined the biological and adopting rela-
tives of adult adoptees who committed suicide and of a similar
group of adoptees who had not. The suicide rate was 11 times
as great in biological families of the adult adoptees who had
committed suicide as it was in the biological families of the adult
adoptees who had not committed suicide. Again, the plausible
explanation is that the suicides of both the adoptees and their
biological relatives, whom they had never met, were related to
mood disorders.
Genes Plus Events Can Equal Depression
Many people have misconceptions about genetic illnesses. Even

if an illness is genetic, that does not mean that other factors do
not play a role in its development. A clear-cut medical example
is juvenile diabetes. As we mentioned earlier, when an identi-
cal twin has juvenile diabetes, in only 15 percent of the cases
does the co-twin also have the disease. Something other than
genes is playing a role, and the chain of events is complicated.
Apparently, individuals with a genetic tendency toward juve-
nile diabetes react abnormally to infection with a common vi-
rus. In these people the virus does not simply produce
respiratory or gastrointestinal symptoms but seems to kill the
cells in the pancreas that produce insulin; the result is diabetes.
However, researchers still do not know why many co-twins do
not develop diabetes, since presumably they have been exposed
to the same virus.
Before discussing the roles of experience and biology, it will
be helpful to clear up some old-fashioned and misleading terms.
In the past, psychiatrists classified some kinds of depression as
reactive—that is, produced by life events in a person who was
predisposed because of a neurosis. Neurosis is a term that has
just about disappeared from modern psychiatry. It was used to
refer to psychological maladjustment that was thought to be
the product of the patient’s abnormal psychological structure,
which in turn was thought to be the product of unfortunate life
experiences. These reactive depressions were contrasted with
endogenous depressions—that is, those depressions produced
within the sufferer. An endogenous depression was believed to
appear for no identifiable reason and was believed to be caused
by abnormal biological functioning in the brain. Reactive de-
pression was treated by and believed to be curable by psycho-
therapy. Endogenous depression was believed to be treatable,
if at all, by physical methods, such as drugs and electroconvul-
sive treatment. So-called neurotic, reactive, and endogenous
depression are labels that are beginning to disappear. One of
the major reasons for their disappearance is the increasing evi-
dence that biological depression and manic-depression are often trig-
gered by life events, but nonetheless are treatable by physical
methods.
As an example, let us consider people who appear to de-
velop a severe depressive illness following the loss of a loved
one or a major disappointment in life. Is the cause hereditary
or psychological? The best evidence indicts both factors. Some
people show a decreased psychological resilience, an inability
to cope with stresses that most people can overcome. A similar
medical situation exists in people who lack normal immunity

to infection with bacteria and viruses. In our parents’ genera-
tion, everyone was exposed to tuberculosis, but only 1 in 3,000
people died of it—people who for unknown reasons were un-
able to fight off the infection. All of us harbor bacteria within
our mouths and our intestines, but we usually do not become
ill from them. However, when immune defenses are lowered—
either genetically (as in the well-known case of the little boy
who had to live in a sterile tent) or by another disease (such as
AIDS)—people do become ill from bacteria that do not bother
others. Presumably, persons who manifest the symptoms of
severe biological depression following a major loss have an
analogous vulnerability—that is, they lack resistance to such
experiences.
This combination of heredity and environment leading to dis-
ease is frequently seen in medicine. An example is a form of
anemia seen in people of Mediterranean extraction. Many Medi-
terranean people inherit a tendency to develop anemia but do
not show symptoms of that disease unless they eat broad beans
or go to a part of the world where they must take a particular
antimalarial drug. Otherwise, they may lead their entire lives
without knowing they have a genetic disease. An example of a
kind of depression with a similar pattern is “seasonal affective
disorder.” People with this disorder become depressed in the
fall and feel better in the spring—apparently in response to the
variation in hours of daylight. Seasonal depression clearly
shows a mixture of hereditary and environmental effects; many
of us become somewhat down during the darker months of the
year, but few of us develop depressive illness.
Can Upbringing and Life Experience

Cause Depressive Illness?
Many psychiatrists, both past and present, have believed that

depression (the type was often unspecified) was produced by
life experience and was best treated by psychotherapy. The first
and most widely listened to proponent of this view was
Sigmund Freud, who began to theorize early in the twentieth

century about the causes of mental illness. The psychoanalytic
theories of depression have focused on unexpressed and un-
conscious (not perceived by the depressed individual) rage as
a reaction to being helpless or dependent on others or to loss of
a loved one. In such situations, it is argued, the patient cannot
express his anger either because of fear of antagonizing the
person on whom he is dependent, or because he does not want
to recognize that the relationship with a deceased (or other-
wise departed) person was not entirely positive. Presumably,
in both instances, the unexpressed anger is kept in and bottled
up, producing depressed feelings. In cases of loss that are ac-
companied by genuine mourning, what distinguishes depres-
sion from grief is that the component of anger is directed inward.
Psychoanalytic attempts to determine the truth of such theo-
ries have been limited and inconclusive. Some investigators
have suggested that abuse and neglect in early childhood can
predispose to depression in later life. The information about
abuse and neglect has come from reports by adults. There are
great difficulties in evaluating retrospective evidence and this
remains an unconfirmed theory. One new prospective study
claims that childhood stress causes depression only in those
with a particular genetic vulnerability.
Two major forms of psychotherapy, less intense psychologi-
cal treatments than psychoanalysis, have advanced different
theories of what causes depression. Two that are particularly
popular at present are the cognitive-behavioral and interper-
sonal theories. The cognitive theory states that patients with
depression have developed the depression because of errors in
thinking—unrealistic attitudes about themselves and the world.
The three major types of thinking “errors” are: (1) undervalu-
ing oneself—low self-esteem stemming from the belief that one
is inadequate and of little value; (2) a negative view of one’s
current experience—depressed people perceive themselves as
unable to achieve their goals and unable to experience plea-
sure; (3) pessimism—the belief that things will not improve. A
depressed person feels depressed because he is constantly put-
ting himself down. Examples of such attitudes are: “I never get
anything right,” or “Every job has to be perfect or it’s no good
at all,” or “Things will only get worse.” These unrealistic ex-

pectations supposedly lead to a person’s recurrent dissatisfac-
tion with herself, which in turn leads to the feeling of depression.
The job of the cognitive therapist is to convince the patient that
there is no evidence for her self-defeating beliefs. The theory
states that such persuasion will change the patient’s distorted
attitudes and help to lift her depression.
The interpersonal theory holds that the basic reason a per-
son becomes depressed is that he does not know how to get
along with his intimate partners. As a result he becomes in-
creasingly disappointed and frustrated. The interpersonal thera-
pist therefore focuses on the patient’s key relationships. The
therapist attempts to clarify how the patient behaves—for ex-
ample, with his spouse or his children or his boss—and how
the other persons, in turn, might be expected to react to his
behavior. The theory proposes that when the patient begins to
understand his effect on others, he can change his behavior and
improve his relationships. This improvement in interpersonal
relationships is supposed to rid the patient of depression.
Are these three theories correct in interpreting behavior and
depression? Proving—or disproving—psychological theories
is extremely difficult. Fortunately, we do not have to ask this
question. We can ask the much simpler question of whether
treatment based on these theories works and—it is a very big
“and”—how does psychotherapy based on these theories com-
pare with medication in the treatment of depression? Fortu-
nately, an elaborate research study of the effect of these
psychotherapies and of medicine on depression was conducted
recently, under the sponsorship of the National Institute of Men-
tal Health. This study was the first of its kind and very impor-
tant, because the two psychotherapies were compared not only
to each other but to a particular drug, imipramine (Tofranil),
and to a placebo pill. Both the imipramine and the placebo were
offered with medication-centered advice and reassurance—that
is, a minimal “case-management” therapy.
What were the results? Unfortunately, the study received
much misleading publicity. The early reports were that cogni-
tive behavior therapy, interpersonal therapy, and drug treat-
ment were all equally effective. A more careful look at the results
by one of us (DFK) came up with a different answer: The out-

come depended on whether the depression was mild or severe.
In the mildly depressed patients, the drug, the placebo, and the
two types of psychotherapy were all equally effective. The re-
sults were quite different in the more seriously depressed pa-
tients. For the severely depressed, medicine was better than
both psychotherapies in terms of quickness, costs, and most
important, degree of benefit. In the severely depressed patients
interpersonal psychotherapy was somewhat more effective and
cognitive behavior therapy slightly more effective than the treat-
ment with the placebo. Furthermore, in patients with marked
dysfunctional attitudes, interpersonal therapy was actually
better than cognitive therapy. It remains possible that other
forms of psychotherapy may work better than cognitive behav-
ior therapy and interpersonal therapy, but they have not been
studied as carefully, and available evidence is unpromising.
Although this study answered the question of how effective
these two psychotherapies are, it did not answer the question
of how effective the best drug treatment is. Only one drug was
employed—imipramine—and it is the common experience of
psychiatrists that many depressed patients who do not respond
to treatment with imipramine do respond to treatment with
other medications. The implication is that, if other drugs had
been used in patients who did not respond to imipramine, the
results would have been even more striking. A recent reanaly-
sis indicated that many of these patients had an atypical de-
pression marked by overeating or oversleeping. This subgroup
did not respond to imipramine, but is known to show a high
rate of response to monoamine oxidase inhibitors (MAOIs),
which, however, were not used.
In light of the relative therapeutic ineffectiveness of these
different psychotherapies, the theory that psychological factors
produce depressive illness remains unsubstantiated.
Chemistry and Depression
The information that supports the view that depressive illness

results from a chemical imbalance comes from studies of both
people and animals; currently, this body of work is being sup-

ported by new techniques, such as the PET (positron emission
tomography) scan, which can measure the degree of metabolic
activity in different brain regions. To provide some understand-
ing of the results of these studies, we will describe in simple
terms the electrical and chemical functioning of the brain.
The brain is composed of perhaps ten billion (ten thousand
million) cells, each of which is connected to hundreds or thou-
sands of other cells by thin strands called axons (“wires”). We
use the word “connected,” but the axons do not actually touch
the other nerve cells; they are separated by very minute dis-
tances. Evolution has worked out a complicated method for
transferring signals from one nerve cell to another. When a nerve
cell is stimulated electrically or chemically, it sends an electri-
cal impulse to the tip of the axon. This electrical impulse does
not stimulate the next nerve cell. Instead, the stimulated end of
the axon releases a chemical that crosses the brief gap and stimu-
lates a second nerve cell. After it has stimulated that nerve cell,
most of the released chemical is picked up again by the axon
that had initially secreted it. In other words, the first nerve cell
acts like a sponge that releases fluid, stimulates the second cell,
and then expands and “sucks” the chemical back into itself.
These chemicals are referred to as neurotransmitters or
neuromodulators. There may be as many as 200 of them, and
many of them are located only in certain parts of the brain. This
means that if one injects an animal with a drug that is like a
neurotransmitter that functions only in one particular part of
the brain, the result is similar to placing electrodes in the nerve
cells of that part of the brain and stimulating it electrically. In
consequence, different chemicals can stimulate different parts
of the brain. For example, if activity of certain nerve cells stimu-
lates an animal to become angry and fight, either electrical
stimulation of those nerve cells by wires or chemical stimula-
tion that affects those nerve cells will make that animal angry.
The relevance for depression is that certain neurotransmit-
ters are known to play a role in the regulation of mood. For
example, studies of the spinal fluid that bathes the brain show
decreased amounts of some neurotransmitters in depressed
persons. Three neurotransmitters seem particularly important
in depression: norepinephrine, dopamine (both very close

chemical relatives of adrenalin), and serotonin. Antidepressant
drugs have very specific effects on these three neurotransmit-
ters. Some antidepressant drugs will prevent the cells that re-
lease norepinephrine from reabsorbing it. As a result, the
norepinephrine remains in the small space between the axon
and the second cell. What this does is unclear. It may cause the
second cell to fire and to stimulate other cells at a greater rate.
An alternative view is that the increase in the neurotransmitter
actually turns off the second cell, and its antidepressant effects
are due to a decrease in the functioning of hyperactive cells.
Other antidepressants prevent the first cell from reabsorbing
serotonin. The two most familiar antidepressants that do this
are amitriptyline (Elavil) and fluoxetine (Prozac).
To use another analogy, antidepressant action seems related
to the fact that the secreting cell maintains a “reservoir” of its
own neurotransmitters and regulates the amount stored by
breaking down excess amounts. Antidepressants such as tra-
nylcypromine (Parnate) and phenelzine (Nardil) prevent the
breakdown of surplus neurotransmitter; in essence, they seem
to enlarge the reservoirs so that stimulation of the first cell re-
leases larger amounts of neurotransmitter, causing greater
stimulation of the second cell. The second cell’s activities are
due to stimulation of its receptors by the neurotransmitter. The
analogy is often made between a key and a lock. The neurotrans-
mitter is a particular sort of key that fits the receptor’s particu-
lar sort of lock. However, this is too static a picture because we
know that receptors can increase or decrease in number and
sensitivity.
Unfortunately, theories about antidepressant function have
some big holes in them. When antidepressants are given to
animals, the effects discussed above are produced in the brain
within minutes, or at most a few hours. But antidepressants
take weeks to work in human beings. Perhaps the long-term
administration of antidepressant drugs is required to increase
the sensitivity of the second cell, so that normal amounts of
neurotransmitter produce larger effects. All of this may require
several weeks. At present, since this research is ongoing, we
just don’t have all the answers.
Norepinephrine, dopamine, and serotonin are not the only

chemicals believed to play a role in the regulation of mood.
Many other chemicals that affect its functioning have been
found in the brain, and many more are believed to exist.
When the brain produces too little of any of these neurotrans-
mitters, either naturally or because of the use of other chemi-
cals, the body appears to deal with the problem by increasing
the number of receptors—in that way the transmitters that are
released have a better chance of taking effect. Examination of
the brains of depressed persons who have died from other dis-
eases reveals an increased number of some of these new recep-
tors. The implication is that the body has responded to a failure
to produce sufficient neurotransmitters by increasing the num-
ber of receptors.
The first well-established antidepressant, imipramine
(Tofranil), has been shown to bind very tightly to the brain—
just as brain chemicals known as endorphins do to endorphin
receptors. This suggests that the brain may have its own imi-
pramine-like chemicals. In fact, such chemicals may be the
brain’s own antidepressants! Another related observation is that
the brains of depressed persons may have a decreased number
of “locks” or receptor sites into which the imipramine can fit. A
decreased number of receptors could produce decreased activ-
ity of these cells, which in turn could lead to depression.
Our understanding of all these matters still remains partial.
One thing we do know is that drugs that make depressed people
normal do not make normal people “high” or manic. They act
like the thermostats in a house that turn on either the furnace
or air conditioner depending on the temperature. Antidepres-
sants lift the mood of the person who is depressed and lithium
and other drugs “lower” the mood of the person who is “high.”
The existence of different kinds of chemical abnormalities
that may underlie depression gives us a clue as to why all de-
pressed individuals do not respond to the same antidepressant.
Psychiatrists routinely find that they may have to try several
antidepressants before finding one that is effective for a par-
ticular individual.
In sum, although we know comparatively little about the
altered chemistry of individuals with depression, our knowl-
edge is advancing rapidly.
Other Illnesses and Depression
Physicians recognize that a large number of medical illnesses

can cause depressive symptoms indistinguishable from those
produced by imbalances in neurotransmitters. Among them are
underactivity of the thyroid gland, mononucleosis, and hepa-
titis. The fact that medical illnesses can cause depression is an-
other reason for requiring that a depressed patient have a full
medical examination.
Some diseases are popularly believed to cause depression but
do not. Two examples are hypoglycemia and allergies. Hypogly-
cemia is an uncommon disorder in which the amount of sugar
in the blood drops to a subnormal level. When this occurs, the
body tries to compensate—for example, by releasing adrenalin,
which raises blood sugar and produces sweating, muscle ten-
sion, rapid heartbeat, and anxiety. There are distinct diseases
associated with hypoglycemia, but they occur infrequently. The
misdiagnosis of hypoglycemia as the culprit responsible for other
diseases (such as depression) is now common; hypoglycemia is
hardly ever the cause of depressive illness.
Another supposed cause of depression is an allergic reaction
to food or to common environmental chemicals. There is no evi-
dence that serious depressive illness is ever produced by such
allergies. Unfortunately, considerable time and money are some-
times wasted pursuing these frequently indicted but unsub-
stantiated claims.
Predicting Depressive Illness
Physicians do not know the chances that any one child will
develop depression, but it has been found, for example, that about
25 percent of the daughters of mothers with depressive illness
will develop depressive illness themselves. This is obviously
distressing, but an awareness of a genetic tendency helps a
concerned parent or the vulnerable individual to detect the
illness when it is beginning to develop. Early detection can
mean early appropriate treatment. The depressed child, ado-
lescent, or young adult may be spared unnecessary pain and
the sometimes cumulative and far-reaching difficulties that stem

from depressive illness.
We want to repeat that depressive illness and manic-depression
do not necessarily follow simple genetic patterns: parents with
one form of the disorder may have offspring with another. De-
pressive illness may skip generations. Both mild and moderate
forms of depressive illness can be genetically transmitted, and
the milder forms, because of their decreased severity, are fre-
quently misdiagnosed as psychological in origin and incorrectly
treated.
Remember, if there is depressive illness or manic-depression
in the family, and if a close relative becomes depressed, or if he
or she develops any severe or unexplained psychological symp-
toms (for example, anxiety attacks, withdrawal, or drug abuse),
it is wisest and safest to assume that he or she may have a de-
pressive illness and to obtain a psychiatric evaluation. Depres-
sion in preadolescents and adolescents may have different
symptoms from those seen in adults—for example, problem
behaviors of various kinds. Therefore, any long-lasting psycho-
logical symptoms deserve careful evaluation.
5
Diagnosis and Treatment of
Depression
Diagnosis
WE HOPE in the preceding pages we have conveyed

to you how important it is to obtain an accurate diagnosis prior
to treatment of depression and related illnesses. Accurate diag-
nosis requires both a general medical and a specialized psychi-
atric examination. Although most patients with depression do
not have another underlying medical condition, the possibility
is great enough so that an initial evaluation must include appro-
priate medical screening. The physical examination should in-
clude the usual blood, urine, and other laboratory tests for the
most frequent abnormalities associated with depression— such
as underactivity of the thyroid gland— and the physician should
also be aware of uncommon, but not rare, conditions associated
with depression, such as hepatitis. If the doctor suspects that one
of these less common medical conditions may underlie the de-
pression, further medical examination is indicated.
It is good practice for patients with mild depression as well as
those with severe depression to receive a medical evaluation.
99
There is no simple relationship between severity and the deter-

mination of whether or not a depression is biological. Most se-
vere depressions are biological, but people who are undergoing
great personal stress (grief, rejection, loss, etc.) may have severe
symptoms. On the other hand, some mild, chronic depressions—
which may seem to be produced by life events—are associated
with widespread loss of interest and pleasure (anhedonia) and
are primarily biological in origin.
In the psychiatric part of the evaluation, the psychiatrist will
inquire about definite signs and symptoms characteristic of
depression and other psychiatric conditions. (Symptoms are
what the patient experiences. Signs are what someone else may
observe, such as weight loss or trembling.) Like the internist,
the psychiatrist inquires about both the presence and absence
of symptoms. For example, the presence of apathy indicates
depression, and the absence of delusions and hallucinations
helps to rule out psychosis. The diagnostician will also be in-
terested in the patient’s life and problems before the present
depression, and in the effects of previous treatments. She often
wishes to interview family members to gain their perspective
on the patient’s difficulties.
Because depressive illnesses often run in families, the psy-
chiatrist will want to know about the pattern of psychiatric
illness within the patient’s family. A relative’s illness may pro-
vide a clue to the diagnosis of a patient whose current illness
is unclear.
The process of sorting out symptoms, signs, and history to
reach a diagnosis, a procedure called differential diagnosis, is es-
sential for proper care. Effective treatments for one kind of de-
pression may be ineffective for another and possibly even
harmful for a third.
The first major question for the diagnostician is whether the
patient has a biochemical depression or a psychological one.
Answering this question requires great skill. Biological depres-
sion can be mild and respond to medication, while a psycho-
logically caused depression may be more severe and yet respond
better to psychological therapy. If the diagnosis is biological
depression, the diagnostician can often recognize particular
Diagnosis and Treatment of Depression 101
forms of the disease that respond better to one type of antide-

pressant medication than to another.
The psychiatrists who are best qualified to make this diag-
nosis have been well trained in modern biological psychiatry.
However, as we mentioned earlier, many other physicians, such
as internists and family practitioners, diagnose and treat de-
pression. Unfortunately, many have not had the training nec-
essary (1) to distinguish between biological and psychological
depression, (2) to determine whether a patient has benefited as
much as possible, nor (3) to use combinations of drugs in pa-
tients who initially obtain only partial relief from their symp-
toms. Indeed, this is still true of some psychiatrists. Similarly,
many well-trained psychologists and social workers are skilled
in the treatment of psychologically produced depressions but
have not been taught to distinguish between biological and
psychological depressions. One’s best chance of getting an ac-
curate diagnosis, therefore, will be from a psychiatrist well
trained in the new biopsychiatry, sometimes called a psycho-
pharmacologist.
After thorough diagnosis the psychiatrist can make predic-
tions about the usefulness of pharmacological (drug) treatment,
psychological treatment, or the combination of the two.
The Effectiveness of
Medical Treatment of Depression
In the previous chapter we discussed the effectiveness of psy-

chotherapy in more serious depression. How effective are the
medical treatments now available? Biological treatments for de-
pression are dramatically effective. Eighty percent, or even more,
of individuals suffering a major depression will respond to one
or another of the antidepressant drugs, singly or in combina-
tion. Of the 20 percent of individuals with major depression who
do not improve when given medication, many will respond to
electroconvulsive therapy. There have been few pharmacological
studies of dysthymia (mild, chronic depression), but it appears
that this condition usually responds to the same antidepressants
used to treat more serious biological depression. Unfortunately,
very little is known about the appropriate treatment of cy-

clothymia (mild manic-depression) since such patients are com-
paratively rare and no research programs have been directed
specifically at this particular illness. Since medication clearly is
beneficial for manic-depressive disease, it is likely that it would
help cyclothymia.
The Decision to Use Drugs, Psychotherapy, or Both:

Relative Costs and Benefits
By his initial evaluation the psychiatrist can predict the likeli-

hood of a given patient’s depression being biological, and if so,
the likelihood of his responding to particular medications. As in
the rest of medicine, perfect certainty is not possible. The facts
he uses are these: Between 70 and 80 percent of people with bio-
logical depression will obtain substantial relief from medication.
This is true of mild as well as more severe biological depression,
whether it has begun recently or has been present for a long time.
There is only slight evidence that specific psychotherapies are
more effective than brief consultations with a physician who fol-
lows no specific psychotherapeutic approach. In a recent study
of the effects of psychotherapy and medication on depression,
conducted under the sponsorship of the National Institute of
Mental Health, practically no differences were found between
cognitive therapy and interpersonal therapy. Both showed only
slight superiority to the placebo treatment that included mini-
mum support. We interpret these findings to mean that psycho-
therapy plays a role in treatment because its offers a very
believable and understandable form of support that is comfort-
ing to the demoralized and suffering patients, but that it is not
actually treating the underlying depression.
Should drug treatment or psychotherapy be tried first? A
good way of answering this question is to evaluate the advan-
tages and disadvantages of four possibilities:
1. The patient is treated only with drugs. Her depression

turns out to be biologically caused, so this is the appro-
priate treatment.
2. The patient is treated only with psychotherapy. His depres-

sion turns out to be biologically caused, so he may waste
considerable time and money.
3. The patient is treated only with drugs, but his depression
turns out be psychologically produced. The treatment is
incorrect. However, this will be determined cheaply and
fairly rapidly (usually within two to three months; if the
patient is part of new drug trials, these rarely extend as
long as six months).
4. The patient is treated only with psychotherapy. Her depres-
sion turns out be psychological in origin, so the treatment
is appropriate.
Another major question concerns patients in category 3, who

do not have a biological depression but who receive drug treat-
ment. All drugs produce side effects—rarely, severe ones. The
risks involved in taking any of the major psychiatric drugs, used
in therapeutic amounts with the recommended precautions, are
probably much lower than the risks of taking penicillin.
Although treatment response is informative if the patient
responds, it is not if he does not improve. If a long-standing
condition improves after taking drugs, that tends to confirm
both the diagnosis and the benefits of medication. However,
there is some trial and error in drug prescription. Patients may
respond to the second or third medication prescribed rather
than the first.
Even failure to respond to all known biological treatments
does not necessarily mean that the patient’s problems are strictly
psychological. It may simply mean that useful biological treat-
ments have not yet been developed for her particular illness.
Similarly, failure to respond to psychotherapy does not nec-
essarily mean that one’s problems are biological, since the fail-
ure may stem from the patient’s inability or unwillingness to
change entrenched ways, or possibly from a mismatch between
patient and type of psychological treatment (or a mismatch
between patient and therapist).
The psychiatrist can discuss the pros and cons with the pa-
tient, whose wishes should be the last word. If a doctor be-
lieves the patient’s choice is unwise, then the patient should
consider another evaluation. Second opinions can be very help-

ful for patients who feel that the doctor’s recommendations are
difficult to accept.
Many physicians prefer to combine psychotherapy and medi-
cation. They believe the medication will relieve the symptoms,
while the psychotherapy will enhance effective social function-
ing. In many instances medicine makes people accessible to
psychotherapy. With the restoration of energy and a zest for
life, biologically depressed patients are far better equipped to
deal with their internal or life problems effectively.
To us, it seems reasonable to start with medication since it is
faster and cheaper and avoids the frustration a biologically de-
pressed person experiences in psychotherapy. Such patients can
be demoralized because they are told if they “work” in therapy
they will get better. Since they don’t get better with psycho-
therapy—their depression persists—they may even conclude that
they are not “good patients” and become more depressed.
We conclude that psychotherapy should not usually be used
as a primary (the first) treatment of depressive illness. Unfor-
tunately, many patients with depressive illness are often mis-
takenly diagnosed, both by psychiatrists and nonpsychiatrists,
as having a depression caused by psychological problems and
are treated with psychotherapy alone. When the depression fails
to respond, many of these therapists then refer the patients to
biological psychiatrists for “adjunctive” medication or “medi-
cal support.”
We think a more reasonable treatment sequence would be to
start with medication. Inappropriate psychotherapy not only
can delay the relief from painful symptoms (with consequent
bad effects on the patient’s personal, vocational, and social life)
but also can make the patient feel even more helpless when the
therapy fails to produce the anticipated improvement. Because
psychotherapy usually provides a plausible explanation for the
depression, the continuation of the symptoms leaves the pa-
tient with a sense of inadequacy and hopelessness.
While the patient is receiving medication, it is useful for him
to spend time talking with his psychiatrist. This enables the
physician to learn more about the patient and his current life
situation. Such knowledge helps the doctor to learn what the
specifics of the patient’s mood disorder are and how his per-
ceptions and functioning are being affected by his illness. He
can then point out to the patient how the depression is affect-
ing other aspects of his behavior. It is one thing to read this
book and learn that many depressives have low self-esteem or
are pessimistic. It is much more meaningful when a psychia-
trist explains to a particular patient how he is devaluing or caus-
ing problems for himself because of excessive caution or anger
or withdrawal. Such guidance and support can enable the pa-
tient to function more effectively and rationally until medica-
tion has had an opportunity to work. Continuing visits are
important because they support the patient in continuing to
take medication. As a first treatment, psychotherapy is prob-
ably most appropriate for nonimpaired, nonsuicidal, nonchronic
depression without the experiences of loss of pleasure and
motivation. Cognitive behavior therapy (CBT) has been exten-
sively recommended. One component of this approach that
seems to have therapeutic effect is its strategy of activating and
energizing the patient. The cognitive techniques, which aim to
change a patient’s dysfunctional ideas and dysfunctional so-
cial strategies, may offer little additional help to those who are
suffering from chronic, disabling depression. There is little evi-
dence that CBT is more effective than placebo.
When psychotherapists refer patients for what they term
“supportive” medication, a further problem sometimes arises
because of conflict over which of the therapists should be in
charge of treatment. We believe that the administrator of medi-
cation should have precedence because of the necessity of ex-
plaining to the patient the likely origin of his illness. The patient
who has been receiving psychotherapy usually has to go
through a process of “unlearning” about the causes of his de-
pression. The psychotherapist may have been emphasizing
factors that are less relevant or even inaccurate. For example,
the psychotherapist may have been focusing on a lengthy ex-
ploration of the patient’s childhood, which in most instances—
contrary to popular notions—has nothing to do with most
severe depressions. Conceivably, for some patients psycho-
therapy may benefit their abnormal physiology, but this is still
speculation.
Some patients may refuse medication for emotional illness

because they see it as a kind of “crutch” that only a weakling
needs. They believe that they should be able to conquer their
problems by will power, taking a deep breath, and keeping a
stiff upper lip. We think that this occurs because the patients
do not understand the causes of mood disorders. (Which is why
we are writing this book!) Rather than embarking on the rela-
tively long process of psychotherapy, the patient should instead
consult a psychiatrist to determine whether medical interven-
tions would make better sense. When maximally effective, such
treatment consists of thorough consultations for several weeks,
followed by less frequent, brief followup visits.
Mild Depressions
Most mild depression is “self-limiting”; that is, it goes away

by itself, without treatment, so that using medication for
mild depression is not always wise. However, chronic, mild
depression—dysthymia—may respond to medication. There-
fore, mild depression should be monitored professionally to be
sure that it does not get worse or become chronic.
Drug Treatment
Many patients have had experience with tranquilizers (such as

Valium or Ativan), sedatives (such as Ambien, Dalmane, etc.),
or pep pills (such as the amphetamines), but not with antide-
pressant medications. The medications used in the treatment
of the biological depressions have characteristics very different
from these more common psychoactive drugs. We describe the
antidepressant medications in greater detail in our chapter on
drugs, but here we want to make some general comments on
the antidepressants as a group.
1. Antidepressant drugs have little effect on normal mood.

When taken by normal persons, they may produce slight
mental slowing; they do not produce a “high.”
2. Antidepressant drugs are “normalizing” in contrast to other

drugs affecting mood. For example, amphetamines, which
are stimulants, produce a feeling of increased wakefulness,
energy, and intellectual activity. If taken by tired, sleepy
people, amphetamines temporarily produce a state of nor-
mal arousal, and if given to people who are normally aware
and alert, they can make them overstimulated (“hyper”).
In other words, amphetamines energize regardless of where
the individual starts.
At the other extreme, sedatives decrease tension whatever

the starting point: if given to overly excited persons, they tend
to calm them down; while if given to people who are neither
tired nor excited, they may put them to sleep.
In describing the major antidepressant drugs as “normaliz-
ing,” we mean that they often make a depressed person lose
his depressed feelings, but they do not have an effect on the
normal person. In this respect they are similar to aspirin. Aspi-
rin lowers a fever but of course does not lower a normal body
temperature.
3. The major antidepressant drugs—both the older and new

antidepressants as well as lithium and the anticonvulsant
drugs—have not been abused because they do not produce
high, elated feelings in normal people, although the anti-
depressants can trigger mania in depressed patients. As we
have said earlier, the older major medications have been
available for more than 35 years and have never been “sold
on the street.”
4. Most patients with depression can stop taking the medica-
tion and remain nondepressed. Patients who do need to
continue taking antidepressants do so because their dis-
ease continues, not because they have become dependent
on antidepressant medication. A depressed patient who
continues to need medication is dependent on it only in
the same way that a person with high blood pressure is
dependent on medication: he must control the symptoms
of a continuing underlying illness.
5. When antidepressants are effective, patients usually con-

tinue to derive benefit from them and do not become toler-
ant to their effects. This also differs from the situation with
abusable drugs.
6. Unlike minor tranquilizers and stimulants, which produce
benefits within an hour, antidepressants and lithium do not
work immediately. The major effects of antidepressants
rarely begin before two to four weeks. Insomnia may sub-
side in a week and appetite may come back in two weeks,
but such symptoms as lack of interest and motivation take
longer to respond. Maximum benefits may take two to three
months to develop.
During treatment, the dosage required may occasionally
fluctuate. If some symptoms recur—such as early morning
awakening—that is a sign that the dose should be increased
before other symptoms reappear.
Many patients grow discouraged and think a drug has
failed because they do not realize it has not been used long
enough to work.
7. Side effects often begin when medication is started, before
the positive effects begin. The side effects usually decrease
with time, but early in treatment the patient may feel that
medication is only making him feel worse.
8. The symptoms of depression may be similar from one per-
son to another, but the presumed chemical abnormalities
that underlie the symptoms may differ. Unfortunately, no
laboratory or chemical tests can as yet predict which drug
will be best for a particular individual. A physician may
have to try several different drugs before she finds the one
that is most effective. Understandably, patients become
concerned when this occurs, but it is a situation familiar in
other branches of medicine. A good example is high blood
pressure. In most instances its chemical causes—like those
of depression—are not well understood. Different patients
with elevated blood pressure may respond very differently
to the same drugs. As with depression, the treating physi-
cian often must try several drugs before he obtains the most
effective one.
Sometimes a drug is effective but the patient finds the

side effects annoying. The newer antidepressants can pro-
duce insomnia, somnolence, weight gain, and impaired
sexual functioning, but these side effects have wide varia-
tion, with some patients experiencing them strongly and
some not at all. The most common side effects of the tricy-
clic antidepressants are dry mouth, constipation, light-
headedness when standing, increased appetite, and weight
gain. They may also affect sexual functioning, but in fewer
patients than the SSRIs. Monoamine oxidase inhibitors
potentially have a more serious side effect that requires
special caution. The physician and patient may want to try
different medications in the hope of getting equal benefits
with fewer side effects.
9. At times, various drugs must be combined. This procedure
is also similar to the treatment of hypertension, which may
require several medications. The use of more than one medi-
cine at a time requires greater clinical skill.
10. The most effective dose—the best dose for each individual—
varies considerably. In extreme instances, some patients
may require 30 times the dose required by other patients of
a particular medication. Some patients fail to respond be-
cause they have been given only a standard dose, since the
treating physician does not realize how much dosage re-
quirements differ. Many patients who have received too
little medication for their particular needs incorrectly con-
clude that the drug is of no use to them.
One of the major problems with treatment by family
physicians and internists is that, even if they have diag-
nosed properly and given the right drug, some tend to be
cautious and administer too low a dose. Others will em-
ploy an adequate dose, but not continue the medication for
a long enough period for it to become effective. Therefore,
patients often tell psychiatrists that they have been treated
with antidepressants that have failed, whereas actually the
medications have not been given a fair trial. Although the
most common difficulty is too low a dose, another treat-
ment problem is that the medications are not given for a
long enough period. Antidepressants cannot be evaluated

in less than six weeks.
11. An important feature of psychiatric drugs is that like all
other drugs, they may “interact” with other medications.
Other drugs may increase or decrease the amount of anti-
depressant that stays in the body. This can result in either
too high or too low levels in the brain. Therefore, it is es-
sential that you keep your psychiatrist informed of all the
medications you are taking that may be prescribed by other
physicians. Ideally, the physicians should consult with each
other prior to any medication changes.
12. Antidepressant medications do not affect the natural history—
the lifespan—of the depressive illness. They control the
symptoms while nature is taking its healing course. In this
respect they are similar to aspirin, which, for example, con-
trols the fever of flu but does not shorten the illness. If
aspirin is stopped too soon, the fever will return. If anti-
depressants are stopped too soon, the patient may relapse.
In order to prevent this, most psychiatrists wait six months
after a depression has responded before they gradually re-
duce the dose. If depressive illness is still present, symp-
toms recur, but an increase in dosage will bring them under
control rapidly. If symptoms do not reappear when the drug
dosage is reduced, the episode of depression has probably
run its course and the medication can be discontinued.
Antidepressant medications do not produce severe with-
drawal problems on discontinuation. It is always advisable
to discontinue any drug slowly. However, if these drugs
are discontinued too abruptly, the worst that happens is
that patients temporarily have flu-like symptoms.
Patients who have had an abrupt onset to their illness
often need only about six months of medication and then
can discontinue without immediate relapse, although they
may have another depressive episode in the future. Unfor-
tunately, as we mentioned before, 20 to 25 percent of pa-
tients will continue to have a mild chronic depression and
may require medication for longer periods. It is likely that
maintenance medication given to prevent relapse should
be given at the same dose level as required for initial symp-
tomatic relief. Antidepressants have been studied carefully

for about 30 years in the treatment of large numbers of pa-
tients. Since negative side effects from long-term treatment
have never been described, we feel relatively comfortable in
the long-term administration of the cyclic antidepressants,
monoamine oxidase inhibitors, and lithium in patients
whose illness is chronic. Our experience with the newer
antidepressants is positive, but we are only now develop-
ing experience with their long-term use. We think that, in
long-term use, they are as safe as the first-generation anti-
depressants, but we do not have the same 40 years of expe-
rience with the new group of drugs. One respect in which
the SSRIs are clearly safer is that an overdose of tricyclics
can be lethal whereas an SSRI overdose is rarely lethal.
13. Even though the medication may have to be taken for a
long time, and the illness may return if the medication is
discontinued, one should not conclude that the medication
is not very helpful. Most chronic diseases, such as heart
disease, diabetes, and arthritis, require continued use of
medication for the preservation of good health. The avail-
ability of long-term medication for the chronic depressive
is a step forward in the treatment of another debilitating
illness.
14. One drug—lithium—requires special mention. Lithium is
the soluble form—the salt—of a metal and is very similar
to sodium, its close chemical relative. Lithium’s special use
is in the treatment of manic-depressive illness. It can in
many cases reduce or eliminate the symptoms of mania and
of associated attacks of depression. When lithium is given,
the dose must be carefully regulated so that its concentra-
tion in the blood is kept within certain limits. Adequate
intake of ordinary table salt is also necessary while taking
lithium. When the dose is adequately regulated, the pa-
tient often experiences no or few side effects. A very few
patients develop kidney problems over many years of treat-
ment. Laboratory tests can determine if this is occurring.
In these few instances, patients can be treated with other
mood stabilizing medications. Lithium is frequently given
on a long-term basis—that is, for many years at a time—as

a preventive drug. Its continuous use can reduce the num-
ber of episodes of recurrent manic or depressive illness that
the manic-depressive patient suffers.
Electroconvulsive Therapy (ECT)
One of the most effective treatments for depressive illness is

electroconvulsive therapy (ECT). Seriously depressed patients
who do not respond to antidepressant medications have a seri-
ous risk of committing suicide. Most of the severely ill patients
who fail to respond to medication do respond to ECT. Recently,
however, there has been considerable concern about the use of
ECT because of the side effects it produced in the past, such as
broken bones and memory loss. The idea has also been voiced
that ECT is a punishment used to control unpopular behavior.
To a great extent, those ideas result from earlier misuse of ECT
(analogous to the misuse of digitalis for supposed “heart fail-
ure”; digitalis is a life-saving but dangerous drug) and lack of
awareness of improvements in the technique.
The failure to recognize that ECT is a medical measure that
can reverse serious, often life-threatening illness goes hand in
hand with the belief that peculiar behavior is really a sane re-
sponse to an insane political and social system. According to
this belief, there is no such disease as mental illness; all treat-
ment of mental illness is only some form of psychological or
behavioral control, and ECT is a particularly punishing form
of such control (the book and film One Flew Over the Cuckoo’s
Nest presented this point of view). As we are emphasizing, how-
ever, the evidence is now overwhelming that there are indeed
biological diseases that produce the disturbed behavior known
as mental illness, and these diseases often require medical in-
terventions. No one knows exactly how ECT works, just as no
one knows exactly how digitalis works in heart disease or
Dilantin in epilepsy, but for suicidal depressive patients who
have not responded to medication, ECT is an essential and of-
ten life-saving treatment. However, it is our impression that
severe “atypical” depressives warrant a trial of MAOIs before

considering ECT.
Most of the serious side effects associated with ECT in the
past have been eliminated by modern techniques. When elec-
troconvulsive treatment was first introduced, patients received
neither anesthesia nor muscle relaxants and were conscious
until the seizure rendered them unconscious. Lying on the bed
awaiting the shock was very anxiety provoking, and patients
became increasingly upset with successive treatments. In some
instances the force of the convulsion was very strong, and the
muscle contractions produced broken bones. Following the
treatment, some patients reported substantial memory loss.
The modern procedure, which has largely eliminated these
concerns, involves the administration of a general anesthetic
and a short-acting muscle relaxant. The patient is asleep when
the therapeutic electrical impulse is delivered to the brain, he
feels nothing, and his body does not convulse. Approximately
two minutes after the administration of the anesthetic, the pa-
tient awakens. He is generally slightly confused, because of both
a barbiturate hangover and the treatment itself. He is likely to
remain tired and to feel somewhat fuzzy for the remainder of
the day. When he has been treated as an outpatient, which is a
frequent practice, someone must drive the patient home.
ECT is usually given three times per week. More frequent
administrations do not seem to increase the rate of recovery.
The total number of treatments required varies considerably
but usually is between six and twelve—that is, the total duration
of treatment is two to four weeks. Following the completion of
the course of therapy, many patients do have some memory defi-
cits for the period before ECT was begun, particularly for the
period of their illness. These memory deficits tend to disap-
pear with time, and in most instances patients suffer little
chronic memory loss. Measuring the extent of the memory
loss is complicated because depression itself impairs concen-
tration and memory; the memory deficits of which the patient
complains may be the product of the preexisting depression
rather than of the ECT. Recent changes in the placement of elec-
trodes—on one side of the head (unilateral) rather than both
sides (bilateral)—have also decreased the amount of memory

loss and temporary confusion.
The major problems still remaining in the administration of
ECT arise from the use of general anesthetic (which always in-
volves some risk) and from the small possibility of permanent
noticeable memory loss. In a person who is physically healthy
except for the severe depression, the risk of a fatal reaction to
the anesthesia is minimal. The risk of memory loss affects people
in different ways. A legal scholar, for example, might be handi-
capped by such a loss, but for many people it would be only a
minor nuisance.
In judging whether ECT is advisable for a particular patient,
one must above all weigh the risks of anesthesia and some memory
loss against the threat of suicide (again, individuals with severe de-
pression have a 10 to 30 percent suicide mortality rate). The presence
of severe impairments, such as inability to eat and prolonged
social and vocational withdrawal, can also affect the decision.
On the whole we believe ECT is underused in depressed pa-
tients who have not benefited from medication. (ECT, however,
is of no value in panic disorder or other anxiety states.)
In some instances of severe depression and mania where elec-
troconvulsive therapy is the treatment of choice, the patient will
refuse to accept such treatment and a decision must be made
by the physician and the family about administering ECT in-
voluntarily. These crises arise infrequently, but in severe illness
the family must be prepared for such a decision.
Psychological Management of Depression
Although we believe that for major biological depression, medi-

cation is the immediate treatment of choice, psychotherapy is
of value in several circumstances. In mild depressions, particu-
larly those that seem related to life stresses, psychotherapy is
often a useful initial treatment (if a complete psychiatric diag-
nosis has ruled out biological depression). It is also helpful as a
supplementary treatment directed at the psychological conse-
quences of severe depression.
Occasionally, psychotherapy has distinct value in helping to

resolve a chronically unrewarding life situation that worsens
depression. In particular, marital counseling may have a role
since unsatisfactory marriages seem extremely common in the
environment of depressed patients. It’s often not quite clear
whether the unsatisfactory marriage leads to the depression,
or vice versa, but anything that makes an unsatisfactory mar-
riage better can only be useful. Also, at times, marital counsel-
ing helps to allow a civilized breakup of a crumbling marriage,
with benefit to both parties.
Psychotherapy for Depressive

Reactions to Life Stress
As we have pointed out, mild depressions can be biological in

origin, but sometimes they are normal human reactions of sad-
ness and grief to unavoidable experiences of loss or disappoint-
ment. In distinguishing depressive illness from ordinary
sadness, the psychiatrist watches for such symptoms of depres-
sive illness as loss of pleasure, appetite and sleep changes, en-
ergy loss, low self-esteem, and guilt.
The diagnosis is not made strictly in terms of the depth of
the depression, because depressive illness can be either severe
or mild, and the same is true of sadness and unhappiness re-
sulting from unsatisfactory or tragic relationships with family,
friends, and employers. Mild depressive illness responds best
to medication, while even prolonged depression resulting from
life’s misfortunes may do poorly on antidepressant medications.
Such unhappiness may respond to time, to change, and, in some
instances, to psychotherapy.
Psychological Therapy for the Patient

Successfully Treated with Medication
The fact that medication is of clearly documented, specific ef-

fectiveness in depressive illness does not imply that additional
psychological treatment is of no value. Even when respon-
sive to medication, the depressive patient may have lingering
symptoms that are complications of the illness itself; sometimes

personal limitations and life stresses contribute to these persis-
tent symptoms. In many instances patients will benefit by a
combination of medication, psychological therapy, training in
new social habits, and possibly even a change of lifestyle.
A frequent psychological consequence of depressive illness,
particularly if the depression has lasted for a long time, is de-
moralization. Demoralization refers to feelings of ineffectuality,
inadequacy at solving problems, and inability to control one’s
life; it can result from biologically produced depression as well
as from external events. The depressed person lacks drive,
motivation, and the ability to face the challenges posed by com-
plex personal problems—and all this can result from the bio-
logical illness. Countless marital and other personal problems
often develop as a result of depressive and manic-depressive
illness. Serious marital problems probably occur in at least half
of the couples in which one member is manic-depressive. In
such situations, couple therapy or family therapy focusing on
such problems may be of benefit.
Psychological problems produced by the illness frequently
outlive the illness itself. They are not neurotic problems. They
are not the result of the person’s incorrect perception of the
world and himself. They are the realistic consequences of his
former inabilities. A medical analogy might be a treated bro-
ken leg. After the bone is healed and the cast is removed, the
patient may have to exercise his leg before he can work nor-
mally again. Although the bone is no longer fractured, the
muscles have weakened and must be exercised to regain their
former strength. Just as weakened muscles are a physiological
complication of such an injury, demoralization can be the psy-
chological complication of depression.
The demoralization produced by depression often disappears
with time, especially in the presence of fortunate and pleasur-
able life experiences. However, psychological therapy may ac-
celerate the process. A variety of other psychologically potent
forces can also help, such as patient support groups, religious
groups, social organizations, consciousness-raising groups, and
encounter groups.
The Relationship of the Doctor and the Patient
In any medical treatment the patient must feel comfortable with

her doctor, and this is especially important in the treatment of
biological depression. The doctor and patient must develop suf-
ficient rapport so that the patient feels free to discuss all of her
medical and psychological concerns. Otherwise such factors as
side effects or unexpected complications in the patient’s personal
life might keep her from following the instructions for taking
the antidepressant drugs and thus seriously limit their effective-
ness. Whether the treating physician is a general practitioner,
psychiatrist, or psychopharmacologist, if the patient is dissatis-
fied with the relationship, she should see another doctor.
The Family’s Role in the Treatment of

Biological psychiatrists differ little in the degree to which they

want the family to be involved when the patient is seriously ill.
They want to explain to the family what the nature of the prob-
lem is, the kind of treatment that is being administered, when
treatment response should be expected, and the alternative
plans that are available if the current treatment program is not
working well. Specific information applicable to depression and
to mania is particularly important to family members. We sum-
marize this information in the following pages.
Depression
In counseling families on how to help a depressive patient, we

try to make several points. First and uppermost, the patient has
an illness.
Second, the patient is not trying to exploit the family mem-
bers. Depressed patients have feelings of hopelessness, de-
creased initiative, and feelings of helplessness. They need help
to perform many activities they could easily handle alone when
well; when the depression becomes more severe, they are un-
able to perform such activities even with help.
Third, as our case examples illustrate, the patient’s illness

can disrupt and disorganize family life. At the simplest level,
for adults, there is often a loss of function. The wage earner
may work less effectively and sometimes cannot work at all.
The housewife neglects her house or children. Depressed pa-
tients can also be extremely difficult to live with. In contrast to
a family member who is psychotic and hears voices or has vi-
sions, depressives have problems that appear to be only exag-
gerations of normal human problems. It is easy for family
members to understand that a psychotic person is ill, but de-
pressed individuals may not seem to have a disease. They
often engender familial unhappiness and anger by being a
“wet blanket.” They do not enjoy things. They do not ini-
tiate activities—they must be pushed or pulled. They do not
fulfill appropriate duties in their relationships. It is difficult
not to see this as laziness or selfishness if the family does not
recognize the real pain involved. The black, pessimistic views
of these patients become tedious. Things are not good, things
never were any good, things will never be any good. They may
be irritable, complaining, a “sour puss.” They are not affection-
ate—in depression, many lose feelings of warmth and love.
Since depressives are uninterested in sex, it is difficult for their
partners not to experience this as rejection and as lack of love.
Other members of the family tend to react with resentment and
anger and to distance themselves from the sufferer. Because
depressed patients have feelings of helplessness and feel in-
creasingly dependent, such reactions, even though completely
understandable, may worsen the depression.
Fourth, in some instances the depressive’s feelings may be
completely unrelated to what is really happening in her life.
The depressive’s business, marriage, and children may be flour-
ishing, and yet she will feel that life is empty and barren. It is
pointless to say, “Look at all you have to live for.” Her feelings
are irrational, and she cannot be argued out of them. When she
says, “I’m no good…. My life has been a failure….Things will
not get better,” telling her that she’s mistaken is not useful and
may add to her demoralization. Notice that we are not saying
that the family members should agree with the patient, but
merely that they should not try to talk her out of her feelings,
since she experiences such arguments as another putdown. It

is useful for family members to tell the patient that they are
sorry that she feels so bad and to remind her that these feelings
are a part of the depressive illness and will eventually dimin-
ish. The family’s job is to maintain optimism and perspective.
The most serious symptom the family must recognize in a
depressed person is suicidal thinking. When a depressive ill-
ness has become that severe, skilled professional help is neces-
sary immediately. The depressed person often—but not
always—expresses the suicidal feelings he experiences, saying,
for example, “Life is not worth living,” or “I’d be better off
dead,” or “Life seems purposeless.” Furthermore, because the
mood of some suicidal patients lifts when they finally decide
to commit suicide, the family should not take an apparent im-
provement at face value. When family members are in doubt, they
should seek a psychiatric consultation at once. When they are in
doubt, they cannot leave matters to the patient. Depressed pa-
tients who are suicidal may, because of their feelings of grave
pessimism, reject any notion that treatment could be of help. In
some instances the depressed patient must be hospitalized in-
voluntarily. If the family suspects that the situation calls for
hospitalization and the patient does not have a psychiatrist,
they should contact the psychiatric crisis unit at a large hospi-
tal. If none are available, they should call the police. In many
localities the police have been trained to deal with psychiatric
emergencies and can help take the depressed patient to an ap-
propriate treatment unit.
Occasionally, a depressed patient may not want the family
involved. If so, he and the doctor should discuss that option
and come to a decision together.
Mania
Sometimes the family recognizes manic illness long before the

patient does. He or she is oblivious to the change from normal
good mood to the euphoria or irritability that increases as the
illness worsens. If the patient has been treated before and espe-
cially if he is under continuing treatment with a therapist, he is
more likely to listen to the family and get emergency help from
his psychiatrist or from a crisis unit. If the patient is unwilling

to comply, the family should obtain expert opinion about the
advisability of involuntary hospitalization. The manic’s behav-
ior may be dangerous not only to himself but to his family as
well because of his impaired judgment. Formerly conservative
individuals may go out on wild spending sprees, speculate with
the family’s savings, impulsively engage in unwise business
decisions, initiate one or several sexual liaisons, and so forth.
This behavior can result in permanent damage to the family’s
finances and destroy the relationship with the spouse or sig-
nificant other.
In extreme cases manic patients may minimize or completely
deny the presence of illness and refuse treatment. In such in-
stances involuntary hospitalization is a must, and the family
should obtain help, either from the patient’s psychiatrist, a fam-
ily physician, the local crisis center, or the hospital emergency
ward. Involuntary hospitalization of the manic patient may be
very difficult for the family because of the patient’s anger and
defiance. Nevertheless, for both the patient’s and the family’s
welfare, treatment is absolutely essential, and the family must
persist in obtaining it regardless of the patient’s objections.
Self- and Family Monitoring of Depression
A patient with depressive illness or mania should learn to evalu-

ate and measure her own mood. The patient usually sees a phy-
sician once a week when a medication has first been prescribed
and is still being adjusted, but after that, visits become less fre-
quent. Therefore, the patient should learn how to determine
if she is getting better or worse, in both her feelings and her
behavior.
Toward this end each patient should learn her own “target
symptoms.” Each individual patient does not necessarily have
all the symptoms seen in depression and mania. Accordingly,
two people may both have profound biological depressions and
yet have only some symptoms in common.
For example, both may have no zest for life—they may have
lost interest in their usual activities and they may often feel sad
and even suicidal. However, one may feel guilty while the other
does not; one may sleep 20 hours a day and the other only four;
one may eat compulsively and gain weight, whereas the other
has a marked loss of appetite and loses considerable weight.
One may be agitated and constantly in motion, while the other
moves slowly as if struck in molasses. The first patient may
skip from subject to subject, whereas the other’s mind may move
so slowly that she forgets her first sentence by the time she has
completed her second. The same variation occurs in mania. One
manic may seem fine and act as if ecstatically happy, while an-
other may be extremely irritable and angry.
In order to evaluate himself properly and to help the physi-
cian to evaluate his progress, the patient should learn the par-
ticular symptoms he gets when he becomes depressed or manic.
Armed with this knowledge, both the patient and the physi-
cian can tell when the depression or mania is improving or
when—say, in a period when the patient has stopped taking
medicine—the first mild but important warning symptoms
appear.
Many psychiatrists will ask a depressed patient how she feels
on a one-to-ten scale—with one as the worst ever and ten the
best. While depressed the patient is likely to assign herself an
unrealistically high number—for example, she might report
that she is much closer to normal than she really is, giving her
mood a “six.” When medication and therapy have restored her
mood to normal, she sees that her previous reports have been
inaccurate—that her mood was really a “three.” This is because
each time the patient is in the middle of a depressed episode
she cannot remember exactly what it was like to feel good. When
she receives effective treatment and returns to her normal mood,
she is surprised how good it is to feel normal.
If one notices improvement, it is helpful to report to the phy-
sician that one feels better this week compared to last week,
but one can feel better and still not be functioning very well.
The real question is how the patient is doing in objective, de-
scriptive terms. How much time is she spending in activities
that she usually enjoys—gardening, playing tennis and bridge,
refinishing furniture? How much time is he spending fishing,
playing chess, finishing the basement, or participating in the
men’s softball league? This is the best way of assessing change

for the better or worse, since depressives forget not only how
good they should feel but what they do when normal.
Although the symptoms of depression and mania are to a
great extent inside the patient’s head, effects of the illness are
clear-cut enough to be visible to an outsider. This means that
other people can be helpful in determining the patient’s progress
or lack of progress. For example, a depressed patient may re-
port that his interest in life is returning and that therefore he is
well on his way to normality, but his spouse can tell the exam-
ining physician how the patient’s interests are still different from
his previous ones.
Similarly, because the depressed patient is often quite un-
aware of her behavior and how it appears to others, her family
may be in a better position to report signs that the treatment
may not be going well—for example, unusual tensions, irrita-
bility, withdrawal, and lack of affection. As we mentioned ear-
lier, this is particularly important if the patient is manic. The
manic’s self-observation is often much less accurate than that
of the depressive, for the illness itself makes him feel good, think
well of himself, be optimistic about his future accomplishments,
and think continuing treatment a waste of time. In addition,
one special caution is necessary with the manic-depressive:
when such patients have been depressed and then begin to re-
cover, they may “overshoot” and become mildly manic—they
exhibit hypomania. Everyone around them may be so pleased
with the disappearance of the depressive symptoms that they
fail to perceive that the patient now has the opposite face of the
illness. It is important to recognize hypomania as a symptom
of illness because of the severe difficulties that may follow.
Self-monitoring and family monitoring are important be-
cause even after a patient has responded well to treatment, his
or her need for medication often fluctuates. On a constant dose,
one patient may experience bouts of depression, while another
may experience periods of pleasant but potentially destructive
highs. This reflects the fact that their disease causes unusual
medical responses. (As we said earlier, individuals not suffer-
ing from depression would experience no such “highs.”) The
treated person with a mood disorder is somewhat like a dia-
betic. The diabetic’s body cannot chemically process the carbo-

hydrate and sugar in his diet, and he must administer the hor-
mone insulin to himself in order to normalize his metabolism.
However, the diabetic’s best dose of insulin depends not only
on the nature of his faulty metabolism but also on the type and
amount of food he eats, his physical activity, and the presence
of other illnesses. All these factors may require him to increase
or decrease his daily insulin dose. The doctor must teach the
patient to measure the effects of these experiences on his dia-
betes and how to adjust his diet and medication himself.
Most biological psychiatrists do not assign such responsi-
bilities to the depressed patient, either because the adjustments
are more complex or because psychiatrists have been more con-
servative in this regard. However, the patient must realize that
his or her need for medication may vary, depending on stress,
illness, and personal experiences. On a fixed and apparently
adequate dose of medication, her psychological motor may not
run smoothly. It may sputter and miss even when it is warmed
up. The patient must learn to observe these misfirings and com-
municate them quickly to the physician, who will help the pa-
tient to adjust her medication. This will minimize fluctuations
in the effectiveness of treatment. Like many other medical treat-
ments, treatment for depression can be very good but does re-
quire constant supervision and adjustment.
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6
A Brief Guide to
Psychopharmacological
Drugs
THIS CHAPTER will provide an overview of the types

of drugs used in the treatment of depression, manic-depression,
and illnesses related to depression (panic disorder and atypical
depression; see next chapter). However, the dosage of the drugs,
whether they should be increased over time, whether they
should be taken on an empty stomach or between meals, the
time of day they should be taken, and the particular side effects
of each should all be discussed in detail with the treating physi-
cian. There are a number of acceptable ways of administering
each medication.
Before describing the major classes of drugs, we wish to make
a few comments about drugs in general.
1. Names of drug classes. The names of drug classes are fre-

quently based on one of their therapeutic effects, but they
may be used in the treatment of other disorders as well. For
example, the drugs used in the treatment of depression—
125
antidepressants—may be used to treat bedwetting in chil-

dren, panic attacks in adults, and excessive shyness in some
people (social phobia).
2. Side effects. Side effects are unwanted, fairly common,
predictable effects produced by drugs. Although side ef-
fects have varying degrees of unpleasantness, they are rarely
life-threatening. Not all drugs have appreciable side effects,
and many produce side effects only in some of the people
who take them. For example, someone who is not allergic
to penicillin (see point 3) will feel no different taking a thera-
peutic dose of that drug than if he had taken nothing at all.
Even very large doses of penicillin produce no side effects
in such people. With aspirin, however, the situation is dif-
ferent. The doses necessary to relieve headache rarely pro-
duce uncomfortable symptoms, but when larger doses of
aspirin are used—such as those that are sometimes neces-
sary to control the pain and inflammation of arthritis—
many people develop side effects such as gastric irritation,
abdominal discomfort, or ringing in their ears. The gastric
irritation produced by aspirin can produce an ulcer, which
in some instances can be dangerous, but this is very rare.
Drugs differ not only in the proportion of people in
whom they produce side effects, but in their range of side
effects. For instance, tricyclic antidepressants cause most
people to develop dry mouth and constipation. We will
discuss the more common side effects and the specific haz-
ards, if any, of the psychopharmacological drugs. Some
drugs that carry side-effect risks are the best treatments for
particular illnesses. In such instances, the physician who
recommends them will carefully monitor the patient at
regular intervals to determine whether drug toxicity is de-
veloping and whether the drug should be stopped. In our
discussion we will identify these drugs and describe the
test procedures.
Even though the Food and Drug Administration (FDA)
will release a drug to the market only when convinced of
its safety and effectiveness, the rare side effect—that is, one
that occurs in less than 1 in a 1,000 cases—cannot possibly
be picked up prior to market release because of the limited
A Brief Guide to Psychopharmacological Drugs 127
number of subjects studied. In order to detect rare side ef-

fects, our society will have to invest the resources neces-
sary to track both the drug use and the drug reactions that
occur after a drug has been released for marketing by fol-
lowing each patient who receives the drug. The entire area
is extremely controversial. The hope of zero risk can never
be achieved. Any drug that helps may on occasion injure.
Poisonous drugs should be removed from the market, but
useful ones should not, and some, like anticancer drugs,
are both poisonous and helpful. The problem is that our
current system allows us to tell one from the other before
market release with regard to common side effects, but is
not effective for detecting rare, and possibly severe, side
effects. Postmarketing surveillance is discussed in more
detail in the final chapter.
The purpose of this book is to help the potential patient
to go about receiving informed professional care. Once the
patient is receiving such care, it is quite understandable
that he or she might wish to know more detail about po-
tential side effects of the medication she is receiving. To
discuss these in detail would obscure the purpose of our
book. Handbook of Psychiatric Drugs, 2004 Edition, by J.
Albers, M.D., Rhoda K. Hahn, M.D., and Christopher
Reist, M.D. (Current Clinical Strategies Publishing,
www.ccspublishing.com/ccs, 27071 Cabot Road, Laguna
Hills, CA 92653-7011) provides a detailed, rational discus-
sion of the variety of side effects that might result from psy-
chotropic drug treatment. Most of these side effects are
trivial and easily managed. If more information is needed
about any particular medication, we heartily recommend
that the reader obtain a copy of Dr. Albers’ book. A valu-
able and authoritative Web site dealing with psychiatric
drugs is http.//www.dr-bob.org/.
3. Idiosyncratic reactions to drugs. Idiosyncratic reactions,
which arise infrequently, can produce life-threatening medi-
cal problems. For example, after repeated treatment with
penicillin, some people develop an allergy to it. Their sen-
sitivity to it is so great that they may develop an allergic
reaction when an injection of a different substance is ad-

ministered from a syringe previously used for penicillin,
even though the syringe has been thoroughly washed and
heated to temperatures above that of boiling water (that is
one of the reasons for using disposable syringes). In rare
instances penicillin allergy produces swelling of the larynx,
which may in turn cause choking and even death. Some
drugs are more likely than others to produce these idio-
syncratic toxic effects.
4. The comparative effectiveness of the antidepressants. An
obvious question is how effective are the different antide-
pressants compared to one another? Another obvious ques-
tion is which of the conditions discussed respond better to
a particular antidepressant than others? The surprising an-
swer to the first question is that there are very few studies
comparing two antidepressants. Most drug studies are
funded by the pharmaceutical industry. They usually do
not want to conduct comparison studies for fear that their
drug will prove less effective than others. They may con-
duct comparative trials if they are trying to break into the
market after their drug has been approved by the Food and
Drug Administration. Such studies are up to the drug manu-
facturer and can be subtly biased in terms of the dosage
they administer of the comparative drug (for example, us-
ing too high or too low a dose). As a result, we do not know
the most effective drugs, nor do we know which is the best
drug to employ if a patient fails to respond to the first drug
tried. With regard to the second question, there are some
depressive disorders known to respond better to one type
of antidepressant than another. An example is adolescent-
onset or chronic atypical depression, which responds to
treatment with the MAOIs, but does not respond to the tri-
cyclic antidepressants.
Since we, in general, do not know which patient will do
best on which drug, we tell depressed patients that there
are several good treatments, that some patients clearly do
better on one drug than another, but there are no tests pre-
dicting the best response in advance of taking a drug. We
may have to try several drugs, and we warn our patients
that they will have to be patient. Jumping quickly from one

drug to another is a self-defeating practice.
5. Combining medications. Because drugs interact with each
other, if a patient takes several drugs simultaneously the
chances for developing side effects are greatly increased.
Therefore, it pays to keep the treatment as simple as pos-
sible. The majority of depressed patients can be satisfacto-
rily treated with a single antidepressant and no other
medication. If patients require multiple medications, this
usually is discovered only after a single medication has
proven ineffective. Some psychopharmacologists com-
monly initiate treatment with three or more different medi-
cations at the same time. We think this is a serious error
and that it would be wise to get another opinion under these
circumstances. If effective treatment for a particular patient
requires the use of several medications at the same time,
such a pattern usually becomes apparent only after succes-
sive steps.
6. Generic drugs. In marketing a new drug, a drug company
assigns it both a generic name related to its chemical com-
ponents and a trade name (brand name). For example, Ciba-
Geigy markets the drug imipramine (generic name) under
the trade name Tofranil. Lilly marketed the drug fluoxetine
(generic name) under the trade name Prozac. Drug compa-
nies patent new drugs that they develop and retain the sole
right to manufacture them until the patent expires. At that
time, any pharmaceutical company may manufacture the
drug, often giving it a new brand name.
A new drug can be marketed only after passing numer-
ous tests reviewed by the FDA, which certifies the drug’s
safety and effectiveness. The FDA’s overseeing of imitative
generic drugs produced after the expiration of the original
patents is less extensive. Effectiveness has already been
documented, and the FDA permits marketing of the drug
so long as it has been shown to be “equivalently available”
to the body—that is, as easily absorbed—as the original
drug. There is some question as to whether such monitor-
ing of generic drugs is always sufficient. The FDA also per-
mits some variation in the amount of the trade-name drug
contained in the new generic: it can range from 80 to 120

percent.
The issue of generic drugs is important both because their
price is often substantially less than that of brand-name
drugs and because of the permitted variations in the amount
of the active ingredients and any additives. Individuals
being switched from a trade-name drug to a generic may
experience overdosage or underdosage. There have been
many letters to psychiatric journals about patients whose
illness recurred when they were switched from the trade-
name drug to the new generic; presumably, they were
underdosed with the generic. Some patients have become
toxic, presumably because they were receiving too much
of the generic drug.
If there is consistent quality control, a generic that var-
ies from the trade-name drug is perfectly acceptable—for
example, if it always contains 120 percent of the brand-name
drug or always contains 80 percent of the brand-name drug.
But if the percentage varies from batch to batch, the patient
will receive different doses of the active medication at dif-
ferent times, even if the label states that the amount is the
same. It should be emphasized that brand-name drugs are
also subject to quality-control problems. It is not uncom-
mon for drug companies—like automobile manufacturers—
to issue recall notices because of defective manufacture.
With these various cautions in mind, it is obviously in
the interest of the consumer to purchase the generic if it is
cheaper than the brand-name product and equally effec-
tive. But we have one more warning here. Because generic
brands may vary among themselves, the patient should be
sure that each time his prescription is refilled he receives the
generic drug produced by a particular company.
A final overall cautionary note. If a patient has been maintained

on the same brand-name drug or the same company’s generic
drug with satisfactory results, and his symptoms recur when
his prescription is refilled, there is a possibility that the quality
control failed and that he has received a batch of defective pills.
The best way to test for this is to have the pharmacist look at
the wholesale lot from which the patient’s prescription was

drawn and to obtain an equivalent medication from a different
wholesale lot.
Side Effects and the

Physician’s Desk Reference (PDR)
Many of our patients look up drugs they are taking on the web
and are sometimes dismayed at the large number of side ef-
fects (often severe) that have been associated with a particular
drug. These side effects are listed in detail in the Physician’s
Desk Reference, also called the PDR, which is really a compila-
tion of the package inserts provided by drug companies for their
products. Before refusing to take such a drug, it is useful for
readers to know the functions of the PDR and how package
inserts are constructed. The important point is that the PDR
“package insert” is not only to inform a physician (or patient),
but to protect the drug company legally. To be marketed, a drug
must be found by the FDA to be effective and safe. This is usu-
ally determined by the results in about 2,000 people. The drug
company then counts side effects on the drug (and placebo)
and divides this number by the number who received the drug
or placebo. This calculates the percentage risks of side effects.
For statistical reasons, one cannot be sure of the presence or
absence of uncommon side effects in such small studies.
When the drug is marketed and physicians begin to prescribe
it, they may notify the FDA or drug manufacturer that they
have treated a patient who developed some unwanted, possi-
bly severe, side effect while on the drug. (But physicians don’t
have to notify, and most do not.) The difficulty is that we can-
not determine the percentage of patients who experience side
effects on the drug, because we do not know how many re-
ceived the drug. After a drug is marketed, no records are made
of everyone receiving the drug so that millions of people may
have received the medication in question. Therefore we cannot
determine the proportion of patients in which a particular side
effect occurs. Its rate of occurrence may be very, very small.
The package insert includes all side effects of which the com-
pany has been notified. It often also includes side effects that
have been reported as occurring in that class of drugs, even if
there has been no such report about this particular drug. The
drug company then publishes a list of these, so that if any pa-
tient anywhere develops what may be a one in a million side
effect, the drug company can state that it listed this side effect
in the package insert, so they cannot be sued for concealing
any of the drug’s dangers. Finally, it is possible that the reported
side effects have nothing to do with the drug and may have
been due to the illness or even another illness. A major public
health advance would be the development of a systematic
postmarketing surveillance system.
The Second-Generation Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs)
These are a familiar group of drugs, of which Prozac was the

first marketed. Some drugs in this same category are Celexa,
Lexapro, Luvox, Paxil, and Zoloft. All are believed to increase
the activity of serotonin, an important neurotransmitter. In gen-
eral, these drugs have fewer side effects than the tricyclic anti-
depressants, though individuals taking SSRIs can experience a
decrease in sexual interest and difficulty reaching orgasm. Many
patients who do not respond to the older antidepressants re-
spond to the SSRIs. But the reverse is also true. Some patients
do not respond to SSRIs, but do respond to older antidepres-
sants. Of the new antidepressants, all SSRIs appear equally ef-
fective. It is not clear if there is any benefit to switching from
one to another, although side effects differ. A problem with all
is that the lowest manufactured drug dose may be too great for
some patients and it is necessary to either dilute them with apple
juice or Gatorade, or cut them up.
Side Effects. The SSRIs produce drowsiness in some people
and agitation and edginess in others. Agitation is described
by some as a feeling of “edginess,” which may be avoided by
taking smaller doses. Some patients, however, simply cannot
tolerate the drug at all. There is also serious concern as to

whether SSRIs may at times increase depression and suicidal
impulses. Some patients have become more depressed—and
even suicidal—while taking SSRIs. This has led to lawsuits. It
is not known whether such reactions were due to SSRIs or were
in spite of SSRIs. Studies that have compared the rate of sui-
cidal ideation and suicidal attempts in patients treated with
SSRIs to that in patients treated with other antidepressants have
not demonstrated any difference. We believe that if such an ef-
fect does occur with SSRIs it is extremely uncommon. It would
be unfortunate if fear of such reactions, which have not been
substantiated, prevented patients from accepting properly
monitored treatment with this useful medication.
Patients with spontaneous panic attacks who are treated with
ordinary doses (20 mg) of Prozac do experience marked in-
creases in anxiety about half the time. Nonetheless, such pa-
tients usually benefit from SSRIs if started with one-tenth to
one-quarter of the standard starting dose. Zoloft also is not well
tolerated in the usual starting dose of 50 mg daily. However,
most patients with panic disorder do seem to be able to tolerate
initial doses of 25 mg daily. Paxil has been reported as tolerable
at 10 mg daily as an initial dose. The starting dose for the other
SSRIs in patients with panic disorder is not known; presum-
ably, they too would have to start at anywhere from one-tenth
to one-quarter of the usual starting dose.
At first, it was thought that Prozac did not produce the weight
gain seen with other antidepressants. Apparently, weight loss
occurs in some people initially but is followed by a return to
normal weight or sometimes by weight gain. Prozac produces
the same adverse sexual side effects as other antidepressants in
roughly one-third of patients, as with the other drugs. These
include decreased sexual desire, decreased erectile potency in
men, decreased vaginal lubrication in women, and either de-
layed or blocked orgasm in men and women. Counteracting
medications can often lessen these effects. After taking SSRIs
for a period of time, some patients experience what has been
referred to as “poop out.” Poop out is not a return of the origi-
nal depressive symptoms. What people report is a subtle loss
of interest and incentive in life. These symptoms can often be
reversed by the administration of the SSRI with certain other

drugs, such as Wellbutrin or a stimulant drug such as Ritalin or
amphetamine. Other patients do experience a return of all of
their symptoms. In some instances, they may respond to an
increased dose of the SSRI, while in others an increased dose
does not produce the initial good response.
Prozac and suicidal preoccupation. After Prozac had been
on the market for some years, there was a report that a small
number of patients became preoccupied with suicide when on
Prozac. All of these patients, however, had been chronically ill
and had suicidal preoccupations previously.
Obviously, it is very difficult when you are treating depressed
people, who are often suicidal, to determine whether a medi-
cation you have given them has increased or decreased their
suicidal impulses or thoughts. Is it because of the medicine or
in spite of it? The only really scientific way to determine this is
to assign a group of patients randomly to the drug in question
or to a standard drug, and then to have the patients evaluated
by psychiatrists who do not know which drug the patient is
on. Such studies, as one might imagine, are extremely rare.
It is well known that any drug may occasionally have un-
pleasant or even intolerable side effects. If the patient is already
in substantial difficulty, the addition of new distress may well
increase hopelessness and suicidal thoughts in an already de-
pressed patient.
Prozac was marketed in a capsule of 20 mg. In most de-
pressed patients, this dosage is well tolerated. However, expe-
rienced biological psychiatrists have found that some people
may become agitated on this dose although they can tolerate a
lower dose.
Recently, there have been frightening claims that paroxetine
(Paxil) and venlafaxine (Effexor) increase suicide attempts in
children. These claims are inaccurate. No actual suicide occurred
in any of the studies in question. What did occur is that on self-
rating forms, approximately 1 percent of placebo-treated pa-
tients reported suicidal thoughts, whereas approximately 2
percent of drug-treated patients stated this.
There has been no published evidence that this small increase
in reports of “suicidal thoughts” is linked to any worsening of
outcome. More important, in the large multisite trials studying

these medications in children, these particular drugs were not
especially useful in treating depression. So for this reason, Paxil
and Effexor should not be used with children and adolescents.
Wellbutrin (bupropion)
Wellbutrin is another recently introduced antidepressant whose

mode of functioning is unclear. Its overall effectiveness is said
to be similar to that of the traditional agents, but there is no
information about its effectiveness compared to the other newer
antidepressant agents.
Side effects. A major advantage of bupropion that distin-
guishes it from other antidepressants is that it does not cause
weight gain or impaired sexual functioning. It also does not
cause drying of the mouth and constipation. Some patients,
however, may become agitated on this medication. It is often a
useful adjunctive medicine for SSRIs, lessening fatigue and
sexual side effects.
Effexor (venlafaxine)
Effexor is a drug that not only inhibits serotonin reuptake, but

in higher doses inhibits reuptake of norepinephrine. Deficien-
cies of norepinephrine in the brain are thought to be a cause of
some depressions, and Effexor, because of its “dual” action on
serotonin and norepinephrine, might be more effective for some
patients. However, this remains speculative. Demonstration
would require a comprehensive research evaluation.
Side effects. If Effexor is begun at too high a dose, patients
often report that they develop diarrhea or nausea. Therefore,
Effexor should be begun at a low dose and gradually increased
slowly enough to minimize these side effects. Other side ef-
fects include dizziness, sleepiness, and insomnia. When doses
of 300 mg or greater per day are reached, blood pressure some-
times increases. For this reason, the physicians will monitor the
patient’s blood pressure. If a patient’s blood pressure is elevated,
but the response to Effexor is favorable, a medication to lower
blood pressure will be prescribed. As with the SSRIs, weight

loss occurs in some people, but is followed by a return to nor-
mal weight and sometimes to weight gain. Effexor produces
the same adverse sexual side effects as the SSRIs in roughly
one-third of patients. Counteracting medications can sometimes
lessen these effects.
Serzone (nefazodone)
Serzone is a relatively new antidepressant whose effectiveness,

compared to the drugs already mentioned, is not known but is
conventionally believed to be effective in a smaller proportion
of depressives. Its two major advantages compared to the anti-
depressants mentioned so far (except Wellbutrin) are that it does
not produce weight gain and does not affect sexual function-
ing. Recently, there have been reports of serious liver failure
and deaths in patients receiving Serzone. The risk is very slight
and it is possible that it can be reduced by obtaining periodic
liver function tests.
Side effects. The most common side effects are dizziness
and lowered blood pressure. Some patients may also experi-
ence muddling of their thinking and problems with memory.
Remeron (mirtazapine)
Remeron is another fairly recent antidepressant. Its effects on

the brain are different from those of any medications discussed
so far, but may involve two neurotransmitters we have seen
before, serotonin and norepinephrine. It lacks the side effects
produced by the SSRIs and Effexor (nausea, insomnia, and
sexual dysfunction).
Side effects. The most common side effects are sleepiness,
increased appetite, weight gain, and dizziness. It tends to make
many patients fat and sedated. A rare side effect may be that it
decreases white cells in the blood, which predisposes to infec-
tion. Any patient taking Remeron who develops the sudden
onset of sore throat, inflammation of the mouth, or high fever
should report this to his physician immediately.
The First-Generation Antidepressants
Tricyclic Antidepressants
The tricyclic antidepressants were one of the first two classes

of drugs used to treat depressive illnesses. They have been used
for 40 years and until recently were the first drugs a psychia-
trist would try with a new depressed patient. They are thought
to work, as mentioned earlier, by preventing the secreting cells
from reabsorbing such neurotransmitters as serotonin and nore-
pinephrine. Some tricyclic antidepressants have a greater ef-
fect on norepinephrine and some a greater effect on serotonin.
Overall, they are almost equally effective, but some patients
will do better on one or tolerate one better than another.
For example, amitriptyline has the greatest sedative effect,
and although useful in some agitated patients, may leave oth-
ers too groggy throughout the day. Other tricyclic antidepres-
sants, such as desipramine or protriptyline, are on occasion
“activating.” Some patients who have been slowed down men-
tally and physically may find that these drugs restore their en-
ergy and relieve their depression, but other patients may
become too agitated by them. These rules are not hard and fast.
Some patients are relaxed or sedated by the “activating drugs,”
while others may be activated by the more “sedative drugs.”
Side Effects. Dry mouth, constipation, blurred vision, low-
ered blood pressure (with dizziness after standing up quickly,
though these medications also can elevate blood pressure),
weight gain, and such sexual side effects as decrease of sexual
desire in men and women, decreased erectile potency in men,
decreased vaginal lubrication in women, and either delayed or
blocked orgasm in men and women are among the most com-
mon side effects.
Management of the effects. After the depression has been
relieved, the physician will often attempt to lower the dose to
see if she can obtain a satisfactory “tradeoff” between symp-
tom relief and side effects. She hopes that the lower dose will
decrease undesirable side effects and still keep the depression
under control. However, recent studies have indicated that pa-
tients may do better during maintenance drug treatment if their
medication level is not cut from their initial treatment dose. It

seems advisable to maintain the dose at as high a level as is nec-
essary, depending on the patient’s particular side effects and how
he tolerates them. Sometimes the side effects disappear with the
passage of time. When they do not, relatively simple techniques
to counteract them are often effective. The dry mouth can be coun-
teracted by sugarless “sourballs.” Light-headedness on stand-
ing up can be prevented by sitting for a moment before standing.
Patients troubled with such hypotension may also have to avoid
hot baths. Increased fluid intake and bulk laxatives (such as
Metamucil) may decrease constipation. Certain drugs (e.g., cypro-
heptadine, urecholine) can be used to relieve the sexual side ef-
fects produced by these agents. To counteract weight gain—which
may come from a decreased “basal metabolic rate”— the patient
must resort to the customary measures of reduced calorie intake
and increased physical activity.
Monoamine Oxidase Inhibitors (MAOIs)
These drugs, introduced at about the same time as the tricyclic

antidepressants, were widely used in Europe, and are used in-
frequently in the United States. The reason for such caution in
the United States was the possibility that, if taken in combina-
tion with certain foods or other medications, these drugs might
produce an episode of dangerously high blood pressure. The
monoamine oxidase inhibitors act therapeutically by prevent-
ing the breakdown of the neurotransmitters dopamine, nore-
pinephrine, and serotonin. They also prevent the breakdown
of tyramine, a constituent of several foods, which is normally
broken down in the intestine before being absorbed. When
MAOIs prevent such breakdown, tyramine enters the blood-
stream, where it can cause a sudden increase in blood pressure,
sometimes to a threatening level. If MAOIs raise blood pressure,
they do so only briefly. They do not produce hypertension—
constant elevated blood pressure.
The MAOIs are very useful agents and are often effective
when other antidepressants are not. Hypertension rarely oc-
curs when a patient follows the dietary instructions. When in-
vestigators discovered what was producing hypertension and
how to prevent it, MAOIs began to be used increasingly in the

United States. Because dangerously high blood pressure can
be avoided by simple precautions, these effective agents are
increasingly used by experienced psychopharmacologists in
early-onset depressions marked by overeating, oversleeping,
lethargy, and rejection sensitivity (atypical depression).
Side effects. Low blood pressure and dizziness after stand-
ing, sleep disturbances, weight gain, and sexual difficulties oc-
cur similar to those seen with the tricyclic antidepressants,
SSRIs, and Effexor, and rapid increase in blood pressure pro-
duced by eating certain foods or by taking certain medications
are among the side effects of this drug group. The sudden rise in
blood pressure that may occur with the MAOIs is distinctive
in that it causes a severe, throbbing headache localized ini-
tially in the back of the head.
Management of side effects. Many doctors give patients on
MAOIs a quick blood-pressure-reducing antidote called
nifedipine (Procardia, Adalat). If the patient develops the severe
pounding headache that accompanies a sudden increase in blood
pressure, he can self-administer this antidote, which quickly low-
ers the blood pressure to normal. The foods the patient on MAOIs
should avoid are those in which there is a large amount of pro-
tein fermentation. This particularly applies to all aged cheeses,
such as Camembert and Stilton. Every doctor who prescribes
MAOIs will provide the patient with a list of foods to avoid. Most
patients do not find this diet unduly restrictive.
Anyone who is receiving MAOIs should tell his nonpsy-
chiatrist physician and should check with a pharmacist before
taking any other prescribed drug or any over-the-counter drugs
(some over-the-counter drugs will raise blood pressure if taken
with MAOIs).
As with other antidepressants, other side effects are man-
aged by dose adjustment; the physician attempts to find a dose
low enough to control the symptoms without producing the
undesired side effects.
Recently, a new class of MAOIs, referred to as reversible
MAOIs, has been developed. One such drug, moclobemide, does
not require dietary restrictions and is currently available abroad.
Other similar drugs are being developed. It is likely that these
agents will prove popular and useful if they come to the United
States market. However, it is possible that concerns about prof-
itability may prevent this.
Desyrel (trazodone)
Trazodone was one of the first of the “new” class of antidepres-

sants. (The only drugs that had been available for years were
the tricyclic antidepressants and the monoamine oxidase in-
hibitors.) It was initially prescribed widely—particularly in
suicidal patients who physicians were afraid might overdose—
because of its safety. Over the passage of time, most psychia-
trists have been disappointed with its effectiveness. For that
reason, and because of a bad side effect described below, it is
now rarely used as an antidepressant. It is still extremely use-
ful as a “sleeping pill.” Even with effective antidepressant treat-
ment, some patients have difficulty falling or staying asleep.
Patients usually become tolerant to other sleeping agents and
require escalating doses, and may become physically depen-
dent on them. Tolerance to trazodone develops slowly, if at all.
However, some patients cannot tolerate the side effects of too
much sedation in the morning.
Side effects. The major disadvantage is that about 1 man in
8,000 who takes the drug may develop “priapism,” a prolonged,
painful erection of the penis. If this is not treated immediately—
by the injection of drugs that terminate the erection—permanent
impotence may result. For this reason many psychopharma-
cologists prefer not to use it in men unless all other treatments
are found unsatisfactory.
Mood-Stabilizing Drugs
Lithium
The discovery of the effectiveness of lithium in the treatment of

manic-depressive disorder was one of the major psychophar-
macological advances of this century; lithium is one of the few
“miracle drugs” in psychiatry. Approximately 70 to 80 percent
of manic-depressive patients respond very favorably to lithium.
As mentioned earlier, lithium is a metal that is a “close rela-

tive” of sodium and potassium, and it is used in the form of a
salt, lithium carbonate (just as salt is used in sodium chloride,
or table salt). Lithium is used to treat mania, to prevent the
recurrence of manic and depressive episodes, and also, in
smaller amounts, to increase the effect of antidepressants (in
this use it is said to “augment” the effects). The most important
aspect of treatment with lithium is a careful adjustment of the
dose so that its level in the blood will be within a certain range.
Too low a level is ineffective, and too high a level will produce
serious side effects. To establish the correct level, the physician
begins with a low dose of lithium and waits until the concen-
tration in the blood is stable, slowly increasing the dose until it
is within the therapeutic range. To determine the blood level
requires periodic blood tests. These should be carried out about
12 hours after the last dose of medication is received. Many
physicians find that lithium is best given in a single dose at
night rather than being spread out during the day. The fre-
quency with which blood tests are taken depends on where the
patient is in the course of treatment. Early in treatment, once or
twice a week is sensible because you are not quite sure what a
given dose will produce in the way of blood level. After a few
months, this should be clear and far less frequent blood tests
become necessary.
Side effects. Minor side effects of lithium may include di-
arrhea, a metallic taste in the mouth, increased frequency of
urination, slight hand tremor, and weight gain.
Two less common side effects require special comment: (1)
About 3 percent of patients receiving lithium develop under-
activity of the thyroid gland. If lithium treatment is working
effectively, the simple and entirely safe remedy is to administer
a small amount of thyroid hormone to bring the blood level of
the hormone to the correct point. (2) In some patients lithium
prevents the kidney from concentrating urine effectively. As a
result, those patients must drink more water than usual and
will urinate more frequently. This is an annoying side effect,
and it is one the physician will monitor. Taking all the lithium
in one dose at night decreases this side effect, and medications
are available to counteract it.
Tests while taking lithium. The regular tests employed at

intervals of four to six months to monitor lithium treatment in-
clude measurement of the lithium blood level, the level of thy-
roid hormones in the blood, the concentrating ability of the
kidney, and kidney function. Although some alterations in kid-
ney function may occur with long-term lithium use, they are
never life-threatening; if lithium proves effective, their inconve-
nience is greatly outweighed by the benefit of the medication.
Precautions. Some routine precautions are necessary while
taking lithium. Lithium is perfectly safe at the right dose, but
may be dangerous if its level is allowed to become too high.
This risk is entirely preventable by monitoring lithium blood
levels and maintaining fluid intake. Early symptoms of excess
lithium in the blood are shaking, trembling, feeling confused,
vomiting, and diarrhea. These symptoms may be brought on
by water loss, which can occur either with intestinal “viruses”
that produce severe diarrhea or vomiting or through severe
dehydration. Such dehydration can be brought on by high en-
vironmental temperatures (as on the beach or in the desert),
vigorous exercise, long periods without drinking, or any com-
bination of these. To maintain correct levels of lithium in the
blood, the patient should drink approximately six glasses of
water a day and not be on a salt-restricted diet. If the patient
does develop a “stomach virus” accompanied by diarrhea or
vomiting, he should discontinue the lithium immediately, in-
crease his fluid intake, and contact his physician.
The necessity for these precautions should not frighten pa-
tients away from the use of lithium. Handled correctly, lithium
is as safe as the medications used for high blood pressure or
the insulin used in diabetes. Like patients with these disorders,
the lithium patient rapidly learns the precautions and danger
signals.
Anticonvulsants
For unknown reasons, some manic patients who respond only

partially to treatment with lithium, or lithium and neuroleptics,
respond to treatment with lithium combined with certain anti-

convulsant drugs.
Tegretol (carbamazepine)
Carbamazepine was the first anticonvulsant drug found effec-

tive when added to lithium in partially responsive manic-
depressive patients. As with lithium, the dosage of carbamazepine
must be adjusted on an individual basis; as the dose is increased,
further tests must be done to ensure that the proper blood level
has been reached (too little is ineffective, but too much may be
toxic).
Side effects. The side effects here include dizziness, drowsi-
ness, unsteadiness, and mental cloudiness. For these reasons
some patients cannot tolerate the drug. A rare serious side ef-
fect occurs in about 1 patient in 50,000: in these patients Tegretol
interferes with the body’s production of blood cells, which can
be life threatening if allowed to persist. Accordingly, the rou-
tine blood tests that are administered when treatment is started
are especially important, and the medication must be discon-
tinued if abnormalities develop. Some psychopharmacologists
suggest that blood tests should be obtained weekly or twice
weekly during the first two or three months, and approximately
every three months thereafter. However, there is considerable
controversy about this; some psychopharmacologists recom-
mend more frequent and others less frequent testing.
Depakote (divalproex)
This anticonvulsant drug is often used for the treatment of epi-

lepsy. Like Tegretol, it is generally added when a manic patient
has responded only partially to lithium. It is begun at low lev-
els, and the dose is kept constant for a few days while the blood
level is measured. The dosage of medication is then gradually
increased until it is within the therapeutic range. Depakote has
proved a particularly successful mood stabilizer. Many psy-
chopharmacologists will use it without lithium, especially in
atypical cases of mania or rapid cycling cases.
Side effects. Among the side effects are drowsiness, weight

gain, and hair loss, which sometimes occur initially. One major
precaution may be indicated in the use of these drugs. They
have been used in severely epileptic infants who were receiv-
ing other anticonvulsants, and some developed liver damage.
Although no liver damage has been reported in adults receiv-
ing Depakote, as a precautionary measure, some physicians
check liver function at periodic intervals by blood testing.
In some bipolar patients, anticonvulsants alone may control
the symptoms. Both anticonvulsants have proved valuable
agents in manic-depressive patients who respond only partially
to treatment with lithium, neuroleptics, and antidepressants.
Depakote has been found by many patients to be even more
easily tolerated than lithium, and many biological psychiatrists
are turning to it as the drug of choice in the treatment of manic-
depressive illness. It’s of interest that it also appears to be help-
ful in patients with very unstable and explosive moods, or
whose moods shift very rapidly between depression and ma-
nia. Unfortunately, it is not as well established as lithium as a
long-term prophylactic agent.
Lamictal (lamotrigine)
This is an anticonvulsant drug that has been used in the treat-

ment of manic-depression. There is some evidence that it may
be effective in treating bipolar patients who are depressed with-
out producing an “overshoot,” causing depression to switch
into mania.
Side effects. Lamictal produces rashes, but if started at a
very low dose—for example 12.5 mg a day—and raised slowly,
this decreases the risk. If medication is discontinued immedi-
ately when a rash develops, the rash usually disappears. How-
ever, some rashes become serious and require hospitalization,
since these rashes may evolve into a serious skin disorder from
which death has occurred. The risk of serious rashes is esti-
mated to be 3 in 1,000. But the risk of death is too rare to allow
a precise estimate. Other side effects are headache, nausea, diz-
ziness, unsteadiness, and double vision.
Topamax (topiramate)
Topamax is an anticonvulsant that has been used to treat bipo-

lar disorder. Experience with it is limited. It has been employed
largely because it does not produce weight gain and may pro-
duce weight loss.
Side effects. Side effects occur in a large number of patients.
These include fatigue, dizziness, language facility problems,
and the development of a “pins and needles” sensation in the
body. Other symptoms include sleepiness, mental slowing, and
difficulties with focusing attention. These side effects are often
confused with depression. This drug requires a cautious ap-
proach and close monitoring.
Newer Anticonvulsants
Other anticonvulsant drugs are reported to be effective in manic-

depression. These include zonisamide (Zonegram), tiagasine
(Gabatril), and oxicarbazepine (Trileptal). Clinical experience
is too limited to accurately determine the effectiveness of these
drugs.
Neuroleptics
Neuroleptics, also called antipsychotics, were the first drugs

effective in the treatment of schizophrenia, the psychosis most
often associated with “insanity.” This illness is still the area of
their major use, but they have also proved helpful in two forms
of mood disorder. First, they are useful in the treatment of ex-
cited manic patients. When patients are very excited, the com-
bination of neuroleptics and lithium works faster than lithium
alone. The neuroleptics can generally be discontinued (while
lithium is continued) when the manic patient achieves normal
mood. The other use of neuroleptics is with depressed patients
who are very agitated. Such patients may suffer from inner feel-
ings of great anxiety and a constant urge to move. These un-
pleasant symptoms are more effectively relieved by neuroleptics
than by tranquilizers such as Ativan.
Side effects. When neuroleptics are administered in large

doses for long periods of time, they may produce alterations in
neurological functioning called tardive dyskinesia, which is char-
acterized by repetitive, involuntary movement. These abnor-
malities are often reversible if the neuroleptics are discontinued.
Since treatment of mood disorders with neuroleptics is neces-
sary with only a few manic-depressive patients and agitated
depressive patients, and is usually brief in those instances, the
risks that accompany high-dose, long-term administration are
minimal. However, should the use of neuroleptics seem advis-
able, the physician should discuss the potential risks and ben-
efits with the patient or the patient’s family.
Atypical Antipsychotics
Zyprexa (olanzapine), Risperdal (risperidone),

Seroquel (quetiapine), Geodon (ziprasidone)
The atypical antipsychotics are a group of novel drugs that were

developed to treat psychosis and produce fewer neurological
side effects. Of them, Clozaril (clozapine) is outstanding as of-
ten improving the status of patients with schizophrenia who
have only partially (or not at all) responded to classical anti-
psychotics. The problem with this medication is that it may in-
frequently produce a fatal blood disorder, agranulocytosis.
Therefore, it is definitely not a first choice medication. Depressed
patients who have responded only partially to antidepressants
may experience improvements when atypical antipsychotics are
added. Atypical antipsychotics have also been found useful in
the treatment of severe mania, often producing improvement
more rapidly than lithium and the anticonvulsants.
Side effects. Although they produce fewer neurological side
effects than the neuroleptics, the atypical antipsychotics do pro-
duce them in some patients. In these patients, there is the risk
that long-term treatment may produce permanent neurologi-
cal changes. The risk of neurological side effects differs among
these drugs. Another side effect, more pronounced in some than
in others, is increased weight. Similarly, some are more likely

to produce metabolic changes when used for some period of
time. Common side effects are sedation, increased appetite, dry
mouth, and lowered blood pressure. Much remains to be
learned about their utility for mood disorders.
Minor Tranquilizers: Benzodiazepines
Benzodiazepines (BZDs) are the common tranquilizers whose

brand names—Valium and Ativan—have entered our popular
language. The several kinds of BZDs on the market differ mainly
in how rapidly they induce calmness after they are taken, and
how long their effects last. The duration of effectiveness of dif-
ferent BZDs ranges from hours to weeks. Making allowances
for their different strengths, all are equally effective, and they
are often useful in the treatment of acute anxiety in depressives.
Alprazolam (Xanax) and clonazepam (Klonopin), which are
very close relatives of the traditional benzodiazepines, have
special utility in the treatment of panic disorder. Unlike the
drugs mentioned previously, benzodiazepines can be abused.
However, most of their abuse has occurred in alcoholics; ac-
cordingly, great care must be used when these drugs are pre-
scribed to treat alcoholics.
A problem with the benzodiazepines is that, when they are
administered for prolonged periods of time, the body may ad-
just to them and become “dependent” on them. If the benzodi-
azepines are then abruptly withdrawn, individuals may suffer
symptoms of agitation and anxiety. Dependence can be avoided
by using benzodiazepines in as low doses as possible, for as
short a period as possible, and by decreasing the dose gradu-
ally when they are being withdrawn. However, for patients with
chronic anxiety, chronic administration may be necessary.
Side effects. The major side effect of this drug group is
drowsiness, which generally disappears with time. A few people
become slightly confused, especially with higher doses. And a
few patients taking BZDs experience memory deficits, which
requires close monitoring by the physician.
There had been media concern about Halcion, a potent, short-

acting benzodiazepine that has been widely used for the treat-
ment of insomnia. The problem is that Halcion, on occasion,
produces a peculiar phenomenon called anterograde amnesia. One
may take a dose of Halcion at night, wake up in the morning,
carry on the activities of the morning, and then in the after-
noon remember nothing about the morning’s activities. From
what we now know, Halcion seems to interfere with the laying
down of recent events into long-term memory when taken in
high doses. In carrying out life’s activities, this side effect is
an annoyance and may even be frightening, but it does not
interfere with one’s daily functioning. The distinction between
short-term memory and long-term memory is of great cur-
rent interest to those trying to understand how our mind
works, but an explanation of this baffling side effect is still
beyond our reach.
Does Halcion represent a substantial risk? The United King-
dom has banned Halcion but the United States has not. Who is
correct? Clearly, we would like to rely on good scientific data,
but there is not a great deal to go on. What is clear is that risk
depends largely on the dosage taken. Our belief is that low doses
of Halcion—that is, one-eighth to one-quarter mg for sleep—
are probably useful for short-term treatment of the vast major-
ity of people and only very occasionally problematic, with
regard to memory, for a small percentage of the population.
The Halcion controversy is another example of how tracking
patients on newly released drugs after FDA approval would
clearly be in the public interest.
Newer Sleeping Agents
Two new sleeping agents are Ambien (zolpidem) and Sonata

(zaleplon). These drugs act quickly and may wear off after three
to four hours in the early morning hours. If taken for periods of
more than one month, patients may become tolerant and re-
quire increasing doses. After repeated use, the patient may find
it difficult to fall asleep without using these agents.
Herbal Remedies
The FDA evaluates new drugs and assesses their purity, effec-
tiveness, and side effects in treatment of particular conditions.
In contrast, herbal remedies are not screened by the FDA and
are available over the counter. The reason herbal remedies have
not been screened by the FDA is because Congress permits their
sale as “nutritional supplements” without evaluation for safety
and efficacy. There are therefore almost no comparisons of herbal
remedies with established treatments and no evaluation of the
nature and frequency of their side effects. Being “natural” does
not mean a substance is safe. In fact, these drugs evolved in
plants to make them bad tasting or poisonous. Morphine, used
to treat pain, and digitalis, used to treat heart failure, are both
derived from plants and are both lethal in overdose.
The herbal remedy reputed to be an effective antidepressant
is St. John’s Wort. St. John’s Wort has been compared to pla-
cebo in the treatment of moderate and severe depression. The
findings were that St. John’s Wort was no more effective in re-
lieving depression than placebo.
Some people have said that although St. John’s Wort may be
ineffective in more severe depressions, it is more effective than
placebo in treating mild depressions. Only when such a study
is conducted will we know if this is true. Being ineffective in
the treatment of moderate depression does not mean that it is
free of side effects. In particular, if a patient taking St. John’s
Wort is treated with an SSRI, he or she may develop a severe
toxic reaction. The frequency of other side effects of St. John’s
Wort is not known, nor its safety when taken over an extended
period of time.
Another popular herb, Ephedra, was just banned by the FDA
for safety concerns.
Monitoring Drug Treatment
There is a complicated issue with regard to the biological moni-

toring of medication through the use of laboratory procedures.
Some biological psychiatrists believe that, by closely monitoring
the blood level, they can achieve the best trade-off between safety
and effectiveness. Other, equally informed biological psychia-
trists believe that these careful measurements are generally not
helpful and that, in fact, the relationship between the blood level
of a drug and the effective level of the drug in that part of the
brain where it works is probably rather poor. Thus, it would be
surprising if such blood measures were of great benefit. In gen-
eral, the measuring of blood levels is primarily for safety rather
than efficacy. For instance, measuring the blood level of lithium
and the anticonvulsants is important because it can get too high
and produce toxicity. To avoid this, we need to observe blood
levels. However, for only very few other psychiatric drugs has it
been shown that monitoring blood levels avoids toxicity. Also,
for very few drugs has it been shown that some minimal blood
level is necessary before you can be assured that the medication
will do its job.
What is the patient to do? Our suggestion is that the in-
formed, skilled biological psychiatrist is most likely to make
sense of confusing data and controversial findings. Your best
chance of arriving at a reasonable conclusion is by working with
someone who knows the pros and cons of the arguments.
7
Illnesses Related to
Depression
THE FOUR SECTIONS of this chapter deal with panic

disorder, which involves a set of symptoms that frequently ac-
companies depression, and three varieties of depressive illness.
Panic and Depression
We are including a discussion of panic disorder in this book be-

cause it is often found in patients with depression. In addition,
patients who experience both panic disorder and depression of-
ten have substantially more difficulty in overcoming their ill-
ness than those who are only depressed. A special problem is
that for such sufferers, panic attacks and their accompanying
chronic anxiety, which we describe below, frequently are the
major complaints. Because most such patients focus on their se-
vere attacks of anxiety, many physicians treat them with minor
tranquilizers such as Valium, which are ineffective in the treat-
ment of panic disorder and depression. Antidepressant medica-
tion, however, is effective for both panic and depression.
151
Therefore, recognizing that a patient has panic disorder can set

him or her on the right treatment road.
Panic, like depression, is a confusing word for most people
because it is part of common speech. One often hears people
who are upset, who are feeling overwhelmed or are thinking of
a difficult future task, say that they are “panicky.”
When psychiatrists use the term panic disorder, they do not
mean ordinary feelings of being anxious or upset but rather a
particular sudden explosion—a crescendo—of physical symp-
toms, usually but not always accompanied by great fear. The
outstanding physical symptoms are heart pounding, shortness
of breath, trembling, a sudden fear of impending death or in-
sanity, and an intense urge to flee. Of special note are the sud-
den onset, which peaks within a few minutes, and the relatively
short duration. Some patients say that their panic lasts for hours,
but they are usually referring to the feeling of fright that fol-
lows the initial panic. That feeling lasts, but the initial fast heart-
beat, shortness of breath, and so on, subside quickly.
Another distinguishing feature of the panic attack is that it
often occurs for no obvious reason. The person may be quietly
walking down the street when she is suddenly struck with an
attack. Such panics are referred to as spontaneous panics. Their
identification is very important because they have a specific
medical treatment.
People who have panic attacks usually think they have sud-
denly become frightened for no apparent reason. Although
much psychological theory has looked on the panic attack as
sudden fear, we do not consider it the same as ordinary fear.
There are marked similarities, such as trembling and sweating,
but the kind of fear that occurs in armed combat is only infre-
quently marked by shortness of breath, which occurs in almost
all spontaneous panics. Furthermore, hormones such as
adrenalin and cortisone, which are normally released during
emergencies, are not released during spontaneous panic. We
are pointing out such differences in order to help in the recog-
nition of panic attacks. Once identified, this illness is one of the
most treatable of disorders.
Occasional panic attacks are probably fairly common. It has
been estimated that 20 to 30 percent of the population have them
Illnesses Related to Depression 153
once in a while. Panic disorder, however, consists of the regular

repetition of spontaneous panic attacks. If a person has had one
attack a week for three or four weeks, he probably has panic
disorder. If he has had only one severe attack but has been thrown
into a state of persistent, apprehensive worry about when the
next panic will occur, that, too, may be panic disorder.
Some patients with panic disorder seem able to go about their
business without undue worry that the panic may recur or with
a feeling of resignation—they believe that if it does recur, they
can withstand it. Others, after several panics, rush to emergency
rooms, develop chronic apprehension, and eventually start
avoiding situations where they could not easily get help if a
panic suddenly occurred. They also begin to avoid places where
they had a panic attack. If a panic occurred at a supermarket,
they avoid the supermarket; if at a church, they avoid the
church. The panics are not produced by being in these places,
but when the first attack occurs in a specific situation, they learn
to avoid that situation. These people begin to avoid driving
through tunnels or over bridges, being in a strange neighbor-
hood, or being alone. Their travel frequently becomes substan-
tially restricted. They may spend more and more time at home,
and some will not venture out without a companion. If they
have to go somewhere—for example, to church—they experi-
ence anxiety when anticipating the return to a place where they
experienced a panic attack. They have been psychologically
conditioned. In the extreme, they become housebound. Patients
with marked life restrictions because of fear of panic are called
agoraphobic. For panic-prone patients whose lives are constricted
in some of these ways, demoralization can be severe.
The following illustrative case narratives have been used in
training therapists in a research study of the treatment of panic
attacks.
5 Edna Elie was a 25-year-old woman who had been liv-

ing and working in Manhattan for four years since college
graduation. She recalls having symptoms of anxiety as a
child, and at that time she was terrified of being in cars,
where she experienced heart palpitations and fear of loss
of control. She attributed her anxiety to the sensation of speed

or rapid motion, and also disliked swings and amusement
park rides.
Nonetheless, as an adult, Edna became a proficient driver.

However, at age 23 she experienced her first spontaneous
panic attack while driving a car. It came out of the blue, and
she experienced feelings of terror and shortness of breath.
Sine the feelings were short lived, she dismissed the experi-
ence and put it out of her mind. A month later Edna and her
boyfriend broke up, and shortly afterward she had a second
spontaneous panic, again while driving a car. This time her
symptoms were worse. She had a rush of terror, difficulty in
breathing, palpitations and chest discomfort; she felt light-
headed and flushed; and she feared that she would faint,
that she was going crazy, and that she was losing control
She had to pull over to the side of the road and have a family
member take over.
In the following month Edna began to have attacks every

week. Since she was now also having them in buses and sub-
ways, she had to take taxis to work.
Two months later, Edna and her boyfriend reunited, started

living together, and got engaged. At about the same time,
her father had heart surgery. Shortly thereafter, she began to
have several attacks every day, mostly “out of the blue,” and
even at home and at work. Eventually she had to quit her
job. She became fearful of going out at all but forced herself
to do so.
After some months, Edna began to feel less energetic, less

interested in activities, more unresponsive to potential re-
wards. Every day became an increasing burden so that she
felt unable to even attempt to look for work.
This case is typical in many ways, First, the subject is a

woman, and women are distinctly more prone to experience
panic attacks than men. Second, she had had a period of anxi-
ety as a child. That appears to be true for roughly half the women
who develop panic attacks in later life. Most frequently, the
childhood anxiety centers around the fear of separation from
the mother, often appearing as a refusal to go to school—a symp-
tom that this patient did not recall. The course of her illness,
however, is again quite typical, with the onset coming unex-
pectedly but seemingly made worse by the threat of important
personal losses. It is also typical that following severe life con-
striction and continuing panic the patient becomes demoral-
ized in the sense of becoming severely pessimistic and
unresponsive to usual interests and pleasures.
5 Tim Thompson was a 26-year-old, single, male high school

teacher who lived alone. He had his first panic attack while
routinely preparing for his class one morning. He felt dizzy,
had difficulty breathing, and had an unusual feeling that
things around him did not look quite real. The feelings of
unreality lasted for about an hour. Over the next several
months he developed weekly episodes, primarily but not
always on the morning of a school day. Typically his head
would swim, he felt distant from what was going on, he had
difficulty breathing and some chest pain, and he feared that
he might be having a heart attack.
He went to several physicians, and all tests were negative.

One physician told him that he was having panic attacks
and stated that medication might be useful. He was relieved
that he did not have a heart condition but refused a prescrip-
tion because he did not like the idea of taking medicine. He
then stopped drinking his regular two cups of strong coffee
in the morning, which resulted in his feeling less anxious.
The panic attacks persisted but were less frequent and less
severe. Tim was still plagued by the idea that he might have
a heart attack, but he continued to work efficiently, did not
have much anticipatory anxiety between episodes, and did
not avoid traveling.
Tim always maintained his ability to enjoy himself and to

pursue his interests. He continued to worry about his heart,
but did not feel fatalistic.
This patient also shows a number of typical features. First,

Time followed the pattern seen in men, who are somewhat less
likely than women to develop the phobias (fear of being alone,
of going out by oneself, etc.). Second, he had caffeine sensitiv-
ity. Although his morning coffees were probably not the entire
cause of his panic, clearly they had made matters worse. Third,
Tim viewed his symptoms as physical in origin but was even-
tually able to gain some reassurance from medical examina-
tions that revealed no serious illness. Finally, he resisted taking
medication for his condition, a common reaction of patients
when psychological symptoms cannot be traced to specific
physical malfunctions. Tim did not become depressed, which
indicated that panic disorder is not simply a variation of de-
pression but rather a related condition.
5 Linda Light, a 38-year-old woman who worked as a hair-

dresser, had her first panic attack at age 33 while at work.
One morning she experienced a sudden, unexplained onset
of fear, accompanied by shortness of breath, palpitations,
chest pain, a choking feeling, dizziness, hot flashes, faint-
ness, nausea, trembling, fear of dying, and fear of losing con-
trol. She thought she was having a heart attack. These feelings
went away in about a half hour but recurred later that morn-
ing. Co-workers drove her to a physician, who examined her
thoroughly and said that all tests were negative, and there-
fore prescribed Valium. The panics continued several times
a week, but Linda took the Valium irregularly, usually wait-
ing until after she had had a panic attack. Her attacks began
to appear in a somewhat less severe fashion, but she wor-
ried about them continuously.
About three months after her first attacks, Linda became

pregnant. She was panic free during her pregnancy. For the
first few years after her daughter was born, she had infre-
quent attacks—about three or four a year—and they were
not very severe, consisting of brief periods of fearfulness,
heart palpitations, and dizziness. She would forget about
them shortly after they were over.
Linda was considering starting work on a part-time basis

and having her mother take care of her little girl when her
attacks came back in full force on a daily basis. Some were
relatively minor, but others were as severe as the first panics.
She sometimes felt so overwhelmed that it took several hours
to recover from the exhaustion and fear that she experienced.
Since she felt that she could not give in to her symptoms and
had to keep the house running, she forced herself to shop and
carry on other activities. However, she cut down her social
activities and felt unable to return to her work as a hairdresser;
she was afraid of having an attack while cutting hair and not
being able to explain what was happening to her.
Linda’s mood varied. At times, when playing with her

daughter, she felt perfectly content and happy. At other times,
when thinking of going back to work, she felt overwhelmed,
despairing, and pessimistic.
This case also has several typical features. Again, the initial
attack “appeared from nowhere,” and the patient developed
fears of a heart attack despite a negative medical workup. A
mild tranquilizer was prescribed and was only slightly help-
ful. The patient lost her symptoms during pregnancy, and that
is typical. This indicates to us that there may be a physiological
basis for the panic attack and that pregnancy provides an anti-
dote. Interestingly, women are also panic free during the pe-
riod of breastfeeding.
The flare-up in Linda’s panic attacks may have been related
to her plans to separate herself from her daughter. She also
developed social phobias—that is, fear of being embarrassed
or humiliated in case she were to have a panic attack while
working. She did not become agoraphobic, and could endure
travel even though she dreaded it.
Note that Linda’s periods of pessimistic despair could eas-
ily be misunderstood as biological depression. This is of some
importance because some antidepressants do not benefit panic
disorder and some antipanic agents do not benefit depression.
Therefore, it is extremely important to determine if a patient
has panic disorder, depression, or both illnesses.
The Nature of Panic Disorder
In explaining panic disorder, some people emphasize biologi-

cal causes for the attacks, while others emphasize a psycho-
logical origin. The psychological explanation is that some people
develop an uncomfortable physical sensation, misinterpret it
as dangerous, and frighten themselves into an attack. Once
having done this, they perceive similar sensations as even more
dangerous, leading to a vicious circle and recurrent attacks.
Our view is that although the vicious circle may make pan-
ics worse, it is unlikely that this is the cause of the attacks, be-
cause some patients have panics while asleep or while relaxing
under safe circumstances, and women are not likely to have
panics during pregnancy or breastfeeding. The rareness of pan-
ics during pregnancy seems especially significant because preg-
nancy is the source of many distressing internal sensations that
could easily be misinterpreted as dangerous. However, we agree
with a psychological explanation for the development of pho-
bias that develop after repeated panic attacks—the learned or
conditioned phobias we have just discussed. Our experience
with the drug treatment of panic attacks strengthens our view
of these separate causes, as we will explain.
In the early 1960s one of us (DFK) discovered that the anti-
depressant imipramine (Tofranil) prevented the occurrence of
panic attacks. However, it did not relieve the fears that devel-
oped as a result of the panic attacks—fears of driving, of leav-
ing the house, and so forth. The fact that imipramine had
knocked out the most serious form of anxiety without affecting
the chronic (and learned) anticipatory anxiety indicated that
these anxieties probably had two different causes. The older
psychological theories about anxiety and panic reasoned that a
patient becomes increasingly anxious until he is finally over-
whelmed by anxiety. But as the case histories show, the chronic
anxiety occurs after—not before—the panic attacks. The patient
is usually feeling reasonably well, although perhaps under some
stress, when a spontaneous panic attack occurs. After repeated
attacks, chronic anxiety develops.
By now there are several useful medications for spontane-
ous panic attacks. Interestingly, these medications do not work
for the person who has what is called a specific phobia. In a

specific phobia, a particular object or situation brings on the pan-
icky feelings. Common examples are fears of insects or snakes.
A person with spider phobia suddenly confronted with a spi-
der may have a wave of terror and suddenly dash away. Be-
cause this kind of triggered panic is not benefited by
imipramine, it is important to distinguish between spontane-
ous panics and other suddenly provoked fearful experiences.
Simple phobias are often benefited by behavioral treatment—
in particular, exposure therapy. In this treatment, the patient is
successfully brought closer and closer to the phobic object with
repeated demonstrations that she is not actually in any danger
and that she can master her fears.
Treatment with Antidepressants
Extensive clinical experience with various tricyclic antidepres-

sants and SSRIs indicates that they probably all work on panic
attacks. As we said earlier, tricyclic antidepressants are safe and
effective. Monoamine oxidase inhibitors (MAOIs) are also ex-
tremely effective in the treatment of panic disorder, but the
possible side effects require special cautions.
Drugs such as Ativan are widely used for the relief of chronic
anxiety and reactions to illness, but they are not particularly
effective against panic. However, two “high-potency benzodi-
azepines” have been found to be effective against panic—
alprazolam (Xanax) and clonazepam (Klonopin). These drugs
have several distinct advantages and one substantial disadvan-
tage. They are quicker to work than the other medications. One
often sees marked benefits within the first week, whereas the
other medications will take from three to six weeks to work.
They have exceptionally few side effects, and most patients can
easily tolerate them, except for some sedative effects at times.
The substantial difficulty is that they produce a physical de-
pendence so that the patient cannot go off the medication
abruptly. The dosage must be lowered slowly under a doctor’s
supervision. During this period there is frequently a recurrence
of anxiety symptoms, and relapse may occur after the medica-
tion is stopped. It is not clear whether the relapse is temporary
or permanent. Nonetheless, for patients who cannot tolerate

tricyclic antidepressants and do not want to run the risk of
monoamine oxidase inhibitors, these agents are tremendously
helpful.
Fluoxetine (Prozac) has comparatively few side effects when
used in the treatment of depression and is tolerated well. How-
ever, about half the patients with panic disorder are markedly
hypersensitive to Prozac. They react to the usual starting dose
of 20 mg as if they have been given a very strong stimulant. A
common patient response is “I feel as if I’m jumping out of my
skin.” This response is also seen in about 10 to 15 percent of the
patients treated with tricyclic antidepressants, but it is more
severe and more frequent with Prozac. We have therefore initi-
ated the practice of starting patients with panic disorder at the
level of 2.5 mg daily (one-eighth of the usual starting dose). We
then slowly raise the dose by small increments to a level that
can control the panics with minimal side effects.
There are as yet no systematic studies of Prozac in the treat-
ment of panic disorder, but our own experience with it con-
vinces us that, in patients who can tolerate it, there are excellent
antipanic effects within four to six weeks.
Zoloft, in initial doses of 25 mg daily, is well tolerated by
most panic patients and appears effective, as is Paxil in doses
of 10 mg daily.
Given all these options, which medications should be used?
We believe that the doctor and the patient should discuss the
pros and cons of each treatment. The informed patient should
be the one to make the decision as to which medication to use,
or whether to use a medication at all. However, most people
who refuse medication do so on the basis of unrealistic anxiety;
it is the doctor’s task to help the patient to become fully in-
formed about the benefits and risks of the medications.
Treatment with Psychotherapy
Once a physical examination has ruled out a medical origin of

panic symptoms, the question arises: can panic attacks and ago-
raphobia be treated by psychological methods, thus making it
unnecessary to use medication? Before the effects of antidepres-
sants were discovered, the most common psychological treat-

ment for agoraphobia was exposure therapy.
Exposure therapy is a behavior therapy in which the patient
gradually relearns to leave her home—that is, to return to the
feared situation. First, she is encouraged to walk outside for a
short distance—say, to the corner—often with the therapist. As
she grows more at ease, she tries longer excursions—around
the block or to a nearby park. Eventually, she can resume tak-
ing buses and visiting neighborhood shops. Finally, she can
again travel alone.
A number of studies have shown that exposure therapy is
effective in decreasing the patient’s phobic avoidance—that is,
the patient no longer avoids the world outside the “safe” home
ground. However, our own and other studies indicate that,
while the phobic avoidance has decreased, the panic attacks
remain. The patients learn to become stoical about the panic—
they learn to endure it. Instead of running home or to an emer-
gency room when they get a panic, they now understand that
the panic attack is harmless, even though very upsetting; many
patients can learn just to sit down and wait for the attack to go
away, and then resume whatever they were doing. In our view,
exposure therapy is not a treatment for panic disorder but a
treatment for the phobias that develop as a result of panic dis-
order. However, once the panic attacks have been controlled
by medication, exposure therapy helps the patient to unlearn
her learned phobias. Now that she no longer experiences at-
tacks, she will overcome her phobias more quickly if she re-
turns to supermarkets, bridges, and other panic-inducing
situations, and “deconditions” herself—that is, learns through
experience that panics do not occur in these places. She may
also learn this through ordinary experience, but learning
through exposure therapy may be considerably faster.
Recently, a behavior therapy for panic attacks has been de-
veloped in which the patient is purposely exposed to situations
in which panic-like symptoms develop—but under controlled
circumstances. For example, patients are given certain demand-
ing physical exercises or rotated dizzyingly in chairs until an
increased heart rate, breathlessness, and nausea mimic their
panic symptoms. This procedure is repeated until the patients
learn not to overreact to these symptoms. These treatments are

frequently combined with a cognitive approach to the panic in
which the patient is trained to understand that the symptoms
are harmless and that the fearful reactions are unnecessary; this
therapy also supports a stoical attitude. Researchers claim that
this technique reduces the number of panics and even produces
cures. Unfortunately, systematic evidence for effectiveness has
only been found in patients with pure panic disorder, who have
not become phobic.
One particularly interesting feature of the behavioral ap-
proaches to panic is training in slow, shallow breathing. This is
usually done with the aid of a relaxation tape. If the patient
suffers only from occasional spontaneous panics, does not have
any of the phobic complications, and recognizes that she is in
no serious danger, then learning how to breathe shallowly at
the rate of 10 to 12 breaths per minute, and doing that for 20
minutes twice a day, may be useful. As usual, this is denied by
some experts.
Atypical Depression
As we indicated earlier in the book, typical depression is usu-

ally characterized by a widespread inability to enjoy life in any
way, marked insomnia, and loss of appetite.
However, researchers have gradually realized that some
patients with contrasting symptoms also suffer from depres-
sion. They respond positively to good things that happen to
them, they are able to enjoy simple pleasures like food and sex,
and they tend to oversleep and overeat. Their depression, which
is chronic rather than periodic and that usually dates from ado-
lescence, largely shows itself in lack of energy and interest, lack
of initiative, and a great sensitivity to episodic—particularly
romantic—rejection by others. Some of these patients also have
occasional spontaneous panics. Extensive studies have shown
that atypical depression is common. Individuals with this dis-
order do not respond well to tricyclic antidepressants, but they
do very well on monoamine oxidase inhibitors. This is surpris-
ing because in “typical depression” both types of antidepres-
sants work well. A case illustration follows. The earlier the on-
set and the more chronic the disorder, the more likely that only
MAOIs will be helpful.
5 Barbara Bahm was a 44-year-old woman who arrived for

treatment complaining of chronic depression since early
childhood. Her longest period of well-being had been dur-
ing her pregnancy and the year after the birth of her first
child. She had a similar period of well-being after the birth
of her second child.
The major symptom accompanying her depression was con-

stant lethargy, with a feeling of leaden heaviness. She fre-
quently overslept by several hours and spent a great deal of
time in bed. She tends to overeat when depressed and had
gained ten pounds in the last year. She does not eat regular
meals, but picks at a variety of junk foods throughout the
day. Although only ten pounds over her ideal body weight,
she felt quite obese.
Barbara’s mood is clearly affected by favorable events, and

she can enjoy a good party. She is sensitive to rejection and
says that feeling rejected makes her angry and depressed.
Her tendency to react in that way has lessened over the years
but initially strained her marriage.
Barbara had a spontaneous panic attack at about age 11, as-

sociated with typical symptoms. Panic attacks have recurred
irregularly since then. However, she has not developed ago-
raphobia. She believes her mother was also chronically de-
pressed, although the details are not clear, and she believes
that her son, now age 20, has symptoms similar to hers. Ex-
tensive psychotherapy earlier in her life decreased some of
her interpersonal and vocational difficulties, but did not re-
lieve her depression or anxiety. Under her doctor’s care, she
tried 150 mg of imipramine, over a few weeks, some years
ago without benefit and was currently taking Valium with
moderate benefit.
Barbara responded well to treatment with Nardil (an MAOI),

becoming energetic, losing weight, and getting along better
with her husband. The panics also ceased. After six months,
she discontinued medication but relapsed quickly. Return-
ing to medication, she once again felt normal.
This patient’s symptoms are characteristic of atypical

depression—chronic lethargy, sensitivity to rejection, over-
eating, oversleeping, and sporadic panic attacks. That she
dates her depression from childhood is somewhat unusual
since most such patients date their depression from adoles-
cence. Her lack of response to imipramine (a tricyclic) and
positive response to Nardil (a MAOI) are also customary.
Since Prozac is a simpler drug to use than Nardil, many pa-
tients with atypical depression are first treated with Prozac.
Recent experience indicates that even if Prozac appears suc-
cessful, these gains are rarely maintained. Also, its use requires
a five-week delay before switching to a MAOI.
Seasonal Affective Disorder
One kind of depressive illness that closely resembles atypical

depression is seasonal affective disorder. Patients with this dis-
order commonly develop symptoms much like those of atypi-
cal depression but only during the periods of the year with less
daylight. They regularly cheer up during the summer. Of great
interest is the fact that exposure to bright light in the morning,
which has the effect of extending the day, has a quick beneficial
effect on many such patients. Monoamine oxidase inhibitors
also help seasonal affective disorder. An example of a patient
with such a pattern follows.
5 Claire Cooper, a 31-year-old, single, freelance art director,

complained of depression, increased appetite, weight gain,
increased sleep duration, low energy, and inactivity begin-
ning in late November each year and lasting through Febru-
ary. Although she first noticed a connection between the time
of year and these problems only a few years ago, she remem-
bers that even as a young girl she thought of winter as “dark
and scary.”
Irritability is a problem for Claire at any time of the year, but

she finds herself avoiding company in winter because she
feels less tolerant and does not want to snap at people.
During such periods she is still able to concentrate while read-

ing books, but she has more difficulty finding one that she
wants to read. She spends most days sitting, sleeping, and
watching TV, and frequently does not get out of the apart-
ment all day. When she is at her worst during the winter, she
may sleep 14 hours a day. Because of her increase in appe-
tite, particularly for sweets, ice cream, and candy bars, she
has put on from 25 to 40 pounds during some winters. Nor-
mally, during the summer she loses some or all of the extra
pounds gained.
Claire has been in therapy several times, starting in the fall

and stopping in the summer when she felt better. When she
heard about phototherapy (bright light treatments), she en-
tered an experimental program that consisted of sitting at a
desk from six to eight o’clock in the morning, reading the
newspaper or doing her work while exposed to a bank of
bright lights. Within a week she rapidly responded to the
treatment. The change was very distinct, with a marked rise
in energy and a decrease in sleep and appetite. She was able
to discontinue the light therapy as the amount of natural
daylight reached the point where her mood would usually
start to improve each spring.
It seems clear that seasonal affective disorder is a biological

illness that, in about half the cases, can be benefited by light
therapy. We are still learning about this disorder. Its symptoms
of oversleeping and overeating closely resemble the symptoms
of atypical depression, already described. Our work has shown
that light therapy is ineffective for patients with atypical de-
pression who do not have a seasonal pattern. On the other hand,
the monoamine oxidase inhibitors, which are effective for atypi-

cal depression, are usually effective for seasonal affective dis-
order. That there are effective treatments is clear.
Premenstrual Syndrome
Women who are thought to have premenstrual syndrome (PMS)

develop a sudden, sharp, unpleasant change in their emotional
state and behavior premenstrually. They are distinguished from
women with an enduring depression by the fact that, when their
menstrual period ends each month, their mood returns to nor-
mal. Prior to their next menstrual period, the same set of symp-
toms recurs. The symptoms of premenstrual disorder differ
substantially from woman to woman. Patients often focus on
their mood disturbance—for example, becoming irritable, an-
gry and impatient, depressed, sad, low, blue, lonely, anxious,
jittery, and nervous. They may also stay home and avoid social
activity. Some patients complain of physical discomfort, includ-
ing abdominal pain, breast pain, lessened sexual interest, back,
joint, or muscle pain, and feelings of being bloated or having
edema. Other patients emphasize decreased energy: they sleep
longer, take more naps, work less, and feel tired and weak.
Another group of premenstrual patients develop a craving for
stimulants (amphetamine), and they may actually have more
sexual interest, greater activity, and increased efficiency. Excel-
lent studies by Jean Endicott and her co-workers have helped
to clear up this confused field by meticulous attention to detail.
They emphasize recurrent premenstrual problematic states. It
is a mistake to talk about one premenstrual disorder. However,
there are various patterns of premenstrual changes that are dis-
tressing and may cause impaired functioning.
One problem with this description is that the symptoms do
not recur with every cycle, and for some women, the premen-
strual emotional unpleasantness occurs irregularly. Clearly, this
produced difficulties for those studying the treatment of PMS.
For example, if one were studying patients who had irregular
PMS and who had just experienced a bad premenstrual epi-
sode, it would be quite likely that, at their next period, they

would be feeling much better. Therefore, if these patients were
then divided into two groups, with one group receiving medi-
cation and the other receiving placebo (a sugar pill) before their
next period, the placebo group would do as well as the medi-
cation group. Until recently, this was exactly what happened in
studies of PMS. Most studies failed to show that medication
was more effective than placebo because so many women with
PMS had “good” months. If they were on placebo they might
feel better than the patients on antidepressants because they
had no side effects. In some studies 80 percent of the patients
receiving drug or placebo did well.
However, better recent studies have required that the diag-
nosis be established by daily ratings across at least two men-
strual cycles. Furthermore, the studies required that for a
diagnosis of premenstrual syndrome the symptoms had to be
associated with at least moderate social or occupational impair-
ment during most menstrual cycles of the previous year. Most
crucially, the daily ratings of symptoms had to demonstrate the
absence of significant symptoms for at least one week post-
menstrually. In studies using this strict definition, a variety of
medications have been shown to be useful, including nortrip-
tyline, alprazolam, and fluoxetine. It appears that fluoxetine—
and probably the other effective SSRIs—need be given only
during the second half of the menstrual cycle.
One of the difficulties about research and diagnosis in this
area is that women with chronic depressive complaints often
claim that they have premenstrual syndrome for two reasons.
First, they have an increase in their symptoms premenstrually.
Second, PMS has tended to be acceptable while depression has
been an illness that has not yet come out of the closet. How-
ever, these patients are really no different from women who
have only chronic depressive disorder. They have similar re-
sponses to antidepressant treatment, and with successful
treatment, both the chronic depression and the premenstrual
syndrome disappear.
In general, women who have premenstrual syndrome with-
out another psychiatric illness have much milder symptoms
than patients who have both chronic mood disorder and pre-
menstrual syndrome. However, some women have no emo-
tional disorder, yet do have distinct and severe changes in mood,
behavior, and functioning during the premenstrual period. It
is evident that women who think they may have a premen-
strual disorder deserve a complete psychiatric evaluation that
is not simply focused on their premenstrual symptoms.
It is also clear that most women do not have a problem with
premenstrual changes. However, patients who do have depres-
sive swings in the premenstrual period are particularly prone
to develop depressions in later life. Therefore, women should
not shrug off a developing depression as simply the result of
their menstrual cycle. Instead, like women with severe premen-
strual symptoms, they should have an evaluation by a profes-
sional skilled in the diagnosis of depression.
8
How to Get Help
ONE OF THE CONFUSING problems that a person with

a depression or related illness faces is finding the right kind of
therapist. Because therapy for various kinds of emotional dis-
orders is offered not only by psychiatrists but also by psycholo-
gists, social workers, nurses, and pastoral counselors, it is
difficult for the potential patient to decide who can best evalu-
ate his needs, help him to plan treatment, and carry it out.
Who Is Most Qualified to

Diagnose and Treat?
The only professionals who can legally dispense medication

for the treatment of psychiatric illness are doctors of medicine
and doctors of osteopathy (M.D.s and D.O.s). The therapists
best qualified to provide all of these services are psychiatrists
with adequate training in biological psychiatry.
All psychiatrists are physicians who have attended four years
of medical school and have had at least a year of postgraduate
general medical experience plus three years of special training
in psychiatry. After a certain number of years in practice, a
169
psychiatrist is eligible to take special examinations, “board ex-

aminations” in neurology and psychiatry, the passing of which
entitles him or her to use the title “board-certified.” Recertifi-
cation at fixed intervals would be a useful method of ensuring
that doctors stay abreast of medical progress. All psychiatrists,
like all other physicians, must continue to attend courses and
engage in other academic activities in order to maintain their
medical licenses.
Among psychiatrists, the best qualified to treat depression
are those who specialize in the diagnosis and drug treatment
of depression, manic-depression, and other biologically caused
psychological difficulties. No formal training programs in bio-
logical psychiatry exist. Psychiatrists master the field as part of
their general psychiatric training or on their own, following
their formal training. Until the past 20 years most training pro-
grams in psychiatry emphasized the psychological causes and
treatment of psychiatric problems (and these programs were
often indistinguishable from those given in social work, clini-
cal psychology, etc.). Thus, older psychiatrists generally have
not had formal training in biological psychiatry. A substantial
number have completely retrained themselves, but many have
not. This is particularly true among the group of psychiatrists
most firmly committed to the psychological treatment of psy-
chiatric problems, such as the psychoanalysts. Many psycho-
analysts, despite their training as physicians, are actively
opposed to the use of medication as the primary treatment of
psychiatric problems.
Many nonpsychiatrist physicians (e.g., internists, family prac-
titioners, neurologists) have also begun to treat large numbers
of depressed patients. There are several reasons for this. Often
depressed patients who have been referred to psychiatrists will
not go, believing that psychiatrists treat only crazy people. They
think that accepting such a referral will mean that they are much
sicker than they had realized, and they believe that going to
see a general physician instead will demonstrate their lack of
serious mental illness.
Sometimes a general physician will treat depressed patients,
either because there are no competent psychiatrists with bio-
How To Get Help 171
logical training in the community or because he has no confi-

dence in the available psychiatrists who specialize in psycho-
therapy. However, for many general physicians, training in the
diagnosis and treatment of depression has been only “on the
job.” Others, particularly family practitioners, may have had a
relatively brief period (three to six months) of training in psy-
chiatry during their post-medical school training (residency).
As we pointed out earlier, general physicians vary tremen-
dously in their skill in handling differential diagnosis, drug
management, and psychological assistance for depression. Some
deal with most routine cases with great ease and are quick to
refer nonroutine cases to biologically skilled psychiatrists. Oth-
ers do not recognize the possible complexity of depressive ill-
ness, approach all kinds of depression in the same way, and
provide inadequate treatment. A further problem is that the
internist or family practitioner may settle for a partial improve-
ment, although more vigorous treatment or alternative medi-
cation might produce complete relief of the depressive illness.
He may then refer the partially improved patient to a psycho-
therapist, who assumes that the remaining problems are psy-
chological. However, because the physician providing the
medication may not have provided optimal medical treatment,
the remaining difficulties may not be psychological problems
at all but biological symptoms that did not yield to the inad-
equate medical management.
If the patient with a mood disorder does not know how to
contact a psychiatrist, he can begin by seeing his family practi-
tioner or internist. He should ask his doctor if he treats mood
disorders or refers people with such problems to a psychiatrist.
If the doctor prefers to treat depression himself, the patient
may decide to remain with him. If the depression does not
resolve completely after two trials of medication, the patient
should request a referral to an appropriate psychiatrist. For
related disorders—manic-depression, panic attacks, atypical
depression—the patient should consult a specialist directly.
Nonphysician therapists, such as psychologists, social work-
ers, and pastoral counselors, are handicapped in treating de-
pressive patients because of their lack of medical training.
Although many have doctoral degrees and postgraduate train-

ing, their education largely focuses on psychological and social
factors in mental disorders. Minimal attention is given to the
all-important biological factors. Social workers usually have
several years of postcollege education, nurses two to four years
of post-high school education that includes varying emphases
of the treatment of other medical and surgical problems, and
psychologists several years of postcollege training in diagnos-
ing and treating patients. Psychologists are often still taught to
use diagnostic techniques that are no longer considered useful
by biological psychiatrists, and they were not trained to recog-
nize biological factors in mood disorders and other psychiatric
illnesses. As we have emphasized, although nonphysician thera-
pists can play a useful role in the treatment of depression, we
do not believe they should be consulted first. In too many in-
stances they may be insufficiently aware of the superiority of
medication to psychotherapy in the treatment of biological de-
pression, and they may fail to make a proper referral.
If the patient contacts a “counseling service” or “mental
health center,” she must be careful that she is not evaluated
only by a nonpsychiatrist. Some such services and clinics still
operate on the basis that all professionals are equally qualified
to diagnose depression. Unfortunately, this is not true, since
many are untrained in diagnosis and cannot make the appro-
priate (necessary) referral to psychiatrists. If the patient is first
seen by a such a “therapist,” she should request a referral to a
psychiatrist, and if this is not made, seek help elsewhere. Oth-
erwise, she may receive inappropriate and ineffective “treat-
ment,” may suffer continuing symptoms, and may never be
referred to a psychiatrist for diagnosis.
A situation that occurs increasingly often as nonphysician
therapists do learn about biological factors is the referral of a
patient by such a therapist to a physician or psychiatrist for
“medical management” of depression or another psychiatric
disorder. In a referral of this kind the physician regulates the
medication while the therapist treats the patient with psycho-
therapy. A possible difficulty with this arrangement is that many
of the “psychological” problems the psychotherapist is treat-
ing may be additional symptoms of only partially treated bio-
How To Get Help 173
logical depression. If so, the monitoring physician may not see

the patient frequently enough to provide the best psychophar-
macological treatment. If the patient is referred by a therapist,
some managed-care organizations will authorize only a one-
hour evaluation (for diagnosis and initiation of treatment) and
ten to fifteen minute follow-up visits.
Here is an example of a possible misunderstanding of this
kind. As we mentioned in discussing possible causes of depres-
sion, psychoanalytic theory holds that depression results from
anger that is held in rather than directed at the person or situa-
tion provoking it. Thus, a psychotherapist might guess that a
depressed wife was not expressing her anger at her husband’s
neglect because she unconsciously thought that expression of
anger would lead to his departure—a situation she feared more
than his transgressions. In such a case, psychotherapy would
be directed largely at “getting the anger out”— helping the wife
to express it. One could then have a situation in which a de-
pressed patient was receiving inadequate antidepressant drug
management while the psychotherapist’s maneuvers were pos-
sibly making her worse. Since excessive anger and irritability
can sometimes be a manifestation of depression, encouraging
the patient to express such emotions might lead to further dis-
tancing from the patient’s family or other close ones. On the
other hand, if the patient was unable to express supposedly
repressed anger (which may not be there), she might see her-
self as a “bad patient,” lowering further her already low self-
esteem.
The possibility of such treatment mismanagement in psy-
chotherapy is what leads us to emphasize that a depressed
patient’s treatment should be directed by a knowledgeable
physician. If a psychotherapist is necessary, the physician can
select one who has learned to distinguish between the psycho-
logical symptoms produced by biological depression, the psy-
chological consequences of a biological depression, and other
psychological problems that the patient may have. Correctly
directed collaborative treatment plays an essential role in deal-
ing with the nonbiological problems that biological depression
produces and with the other psychological problems that pa-
tients may have simply because they are human.
Finding a Psychiatrist with

Training in Biological Disorders
A logical way to begin looking for a biologically trained psy-

chiatrist is to request a referral from one’s family physician. If
the physician has not had much professional contact with psy-
chiatrists in the community, one can inquire of the state or dis-
trict branch of the American Psychiatric Association (APA). The
branch will give the inquirer the names of several psychiatrists
practicing in the community. The names are usually given on a
rotation basis, and the caller can ask whether the psychiatrist is
board-certified or not. However, the APA or district branch will
provide no evaluation of the psychiatrist’s skill, areas of spe-
cialization, or interest and training in biological psychiatry.
Another especially good way to locate specialists in the bio-
logical treatment of depression is to find out if any nearby uni-
versity medical schools have a research or treatment clinic for
depression (or “mood disorders” or “affective disorders”). Such
clinics generally not only conduct research but evaluate new
drugs and train young psychiatrists in the diagnosis and treat-
ment of depressive illness. The level of expertise in these clinics
is usually high, and they are often able to recommend not only
their own staff but psychiatrists practicing in the community.
If the university medical school does not have such a clinic,
it is sometimes helpful to ask whether any of the senior staff or
members of the Department of Psychiatry see private patients.
However, physicians associated with medical schools are not
necessarily better trained than physicians in the community.
The odds are greater that a physician chosen at random is well
trained if associated with a medical school, but some senior
physicians at medical schools still emphasize the psychologi-
cal approach to psychiatric problems. We wish to emphasize
that there are many excellent, biologically skilled psychiatrists
in the community who are not associated with medical schools.
We refer patients to such psychiatrists all the time; some of them
are in private practice and some are in good private clinics that
specialize in depression.
Many communities have community mental-health clinics,
which are supported by federal and state funding and that of-
How To Get Help 175
fer psychiatric services on a sliding-fee scale. The philosophies

of the clinics and the expertise of their psychiatric staffs vary
considerably. In very many, evaluation is done by non-
psychiatrists. In others, all evaluations are done or reviewed
by psychiatrists. Community health clinics have the advantage
of lower fees, but the prospective patient must ask the same
questions of them that she would of any private psychiatrist.
In addition to these avenues for getting help, several national
organizations provide assistance.
The Depression and Bipolar Support Alliance consists of
patients and families who try to educate the public about de-
pression and bipolar disorder and to help prospective patients
obtain adequate therapeutic help. The central branch responds
to requests for help by referrals to convenient local branches
that maintain lists of physicians whom their members have
found helpful. It does not attempt to certify the excellence of
the doctors; however, the association’s recommendations, based
on experience, are very useful. (Address: 730 N. Franklin Street,
Suite 501, Chicago, IL 60610. Telephone: 800-826-3632.)
Meeting with the Psychiatrist

for the First Time
In the first interview, which will probably take an hour or two,

the prospective patient should ask the psychiatrist about his or
her approach to therapy. In particular, it is vitally important to
find out what the doctor’s policy is regarding the use of medi-
cation. An open-minded psychiatrist will not think that such
questions are presumptuous and will not conclude that the
patient is resisting recognition of possible psychological prob-
lems. If the psychiatrist does seem to resent such inquiries, we
recommend that the patient seek another psychiatrist.
Before being seen in psychiatric consultation, the patient
should prepare a detailed list of all treatments, including
medications of any sort, that he has received for any medical
or psychological conditions. The actual dates and dosages of
medications are crucial for evaluating past treatment. Memory
is unreliable with regard to such information. The patient should
check with his physician or pharmacist to get the exact names,

dates, and amounts.
Depending on the severity of the depression, the psychia-
trist may see the patient initially twice a week for two or three
weeks, then once a week for a few weeks, and at decreasing
intervals thereafter. Psychotherapy is not a necessary compo-
nent of the initial treatment of biological depression, but the
patient and doctor may wish to discuss it. The patient should
be sure to raise any questions he may have about his type of
mood disorder.
At the outset it is also desirable to discuss openly how the
progress of the therapy will be evaluated. An increasing num-
ber of psychiatrists now find this approach acceptable, some
even draw up contracts with their patients specifying the du-
ties of both participants, the frequency of the meetings, and the
point at which progress will be evaluated in order to determine
whether the treatment should continue.
Second Opinions
How long should one stay in treatment that is not helping? Over
80 percent of patients with a mood disorder will respond to at
least one of three drugs, if each is tried in adequate dosage for
a minimum of six weeks. The degree of response may vary con-
siderably. Some patients will experience complete relief of
symptoms, others will have some decrease in symptoms, and
about 20 percent of properly diagnosed and properly treated
patients will fail to respond.
As explained previously, all patients should have an ad-
equate medical examination prior to embarking on a course of
medication. If medication has failed to be effective, there should
be an even more intensive medical review. In particular, the
physician will want to determine if the patient has a mild de-
gree of hypothyroidism. Among its many functions, thyroid
hormone affects not only metabolism but also the way the
brain functions. Borderline underactivity of the thyroid gland
can be detected only by special medical tests. These tests have
demonstrated that, in many instances, a lack of response to
How To Get Help 177
standard antidepressant treatments is due to hypothyroidism.

Often the addition of thyroid hormone “potentiates” the anti-
depressant and relieves the depression.
If a patient has received three trials of medicine of six weeks
each and does not feel any better, she and her psychiatrist should
discuss obtaining a second opinion. If progress is not apparent,
or if in open discussion the psychiatrist acknowledges uncer-
tainty, it is perfectly appropriate for a patient to request a sec-
ond opinion, a consultation. This does not necessarily reflect
on the competence of the psychiatrist. It is merely a recognition
of the fact that no physician can know everything and that some
patients’ problems can be exceedingly perplexing.
The preceding discussion has assumed that initial treatment
has been by a biologically trained psychiatrist. If a patient with
the symptoms of unipolar depression (loss of pleasure, loss of
interest, loss of energy, etc.) has been in psychotherapy for over
three months with a nonbiological psychiatrist or a non-
psychiatrist and has not responded, he or she should obtain a
consultation from a psychiatrist who offers biological treatment.
Even if the symptoms are unclear and the therapist cannot be
certain that the patient is depressed, such a consultation is ad-
visable. Any patient with manic symptoms should consult with
a biologically trained psychiatrist immediately.
Recently, the United States Department of Health and Hu-
man Services has released an excellent document, titled “Clini-
cal Practice Guidelines” for the treatment of depression. It states,
with regard to psychotherapy, that “If there is no symptom
improvement at all within 6 weeks, the choice of treatment
modality should be reevaluated. For patients who improve but
who are still symptomatic after 12 weeks, treatment with medi-
cation is a strong consideration.”
Some patients with depression, like some patients with hy-
pertension, are extremely difficult to treat. With these patients,
even a skilled physician may have to try several medicines
singly and in combination before he finds a recipe that works
for a given patient. It is hard for a patient to distinguish be-
tween a good physician who is systematically trying medicines
and a poorly educated one who may be prescribing in a non-
systematic way. However, whenever the patient has doubts
about a treatment to which he is not responding, it is sensible

to request a second opinion.
Psychotherapy for the Depressed Patient
When a patient who is receiving adequate and successful medi-

cal treatment for depression still has several psychological diffi-
culties (demoralization, various day-to-day problems consistent
with life circumstances, learned maladaptations), it would be best
if the patient’s psychiatrist could also handle the psychological
requirements. However, adequate training in both the biological
and the psychological aspects of psychiatric illnesses is uncom-
mon, which makes finding well-rounded therapists difficult for
patients and for referring physicians and agencies. We ourselves,
when asked to refer a patient for treatment in a distant city, often
must ponder long and hard in order to locate appropriate psy-
chiatrists. We do not have too much difficulty in locating a phy-
sician for a patient with a clear-cut biological depression or a
reputable psychotherapist for someone with personal limitations
or maladaptations that are clearly psychological in origin. But
when the patient’s problems are a variable mixture requiring
careful biological and psychological evaluation, finding an ap-
propriate physician can be very hard.
We would like to emphasize that, in such instances, biologi-
cally trained psychiatrists often turn to the many well-trained
nonmedical psychotherapists, recommending psychologists,
social workers, or others who are equipped to carry out the
necessary psychotherapy for depressive patients. Sometimes
psychiatrists also recognize that patient support groups, reli-
gious groups, and social organizations can provide the neces-
sary support for patients with depression who have special
psychological needs.
Conclusion
In closing, we would like to offer one last piece of advice to the

depressed patient receiving therapy, who is like any other medi-
How To Get Help 179
cal patient receiving therapy. It was advice—a “law”— dispensed

by one of the grand old men of American internal medicine to
his medical students and interns: “If what you’re doing is work-
ing, don’t stop; if what you’re doing isn’t working, try some-
thing else.” Profound wisdom, simply stated.
As scientists and clinicians, we are appalled because depres-
sion and manic-depression affect so many people. Even when
treated, they are too frequently inadequately treated. This al-
lows unnecessary pain, impairment and, tragically, too many
deaths. As working clinicians, we are frequently heartened by
our ability to radically improve the lot of confused and suffer-
ing people. As scientists, we have shown that our treatments
are real, effective, and not simply wishful thinking.
The stigma of mental illness has interfered with proper, hu-
mane, and rational care of emotional disorders. This has been
confounded by the discrimination against mental illness car-
ried out by funding agencies, in the form of both private insur-
ance and underfunded public mental-health organizations.
Proper attention to clinical depression will lower medical costs,
increase productivity, and provide solace to the many suffer-
ing from depression.
We hope this book will help individuals with undiagnosed
depression and manic-depression to recognize their illnesses,
to understand them somewhat better, and to seek and receive
appropriate treatment.
Epilogue
What Don’t We Know?

What’s Blocking Progress? What to Do?
WE HAVE BEEN scientists and psychiatrists for over

50 years, and in that time much medical progress has taken
place. But what we have learned is that chance observations
often lead to clinical breakthroughs that can only be recognized
by the prepared mind of a clinician—what is known as “seren-
dipity.” That many of the major advances in psychiatric medi-
cation have been serendipitous comes as a surprise to even
well-informed people. Frequently, psychiatric medications pro-
duce unanticipated benefits that don’t fit current theories or
clinical expectations. These remarkable benefits were respon-
sible for changing our diagnostic system and allowing im-
proved, more specific medications to be prescribed.
Over five decades we have studied emotionally ill people
and their treatment. Paul did pioneering, creative studies in
the vastly unpopular area of medication for children, wrote the
first book on ADHD (attention-deficit hyperactivity disorder) in
children, was the first to diagnose ADHD in adults, and demon-
strated the effectiveness of stimulant treatment; and Don found
181
182 Epilogue
a remarkable benefit from using the first widely used antide-

pressant, imipramine, on spontaneous panic attacks, which led
to the concept of panic disorder, as well as proving the value of
the concept of atypical depression.
Our point in bringing up our research history is to under-
score that these and other therapeutic advances came directly
from detailed long-term studies of sick people, whose various
treatments sometimes worked and sometimes made matters
worse. Unfortunately, current psychiatric research programs
have turned away from this fruitful clinical approach to dis-
covering new treatments to focus almost exclusively on basic
laboratory studies. But these types of studies still have only a
tenuous relationship to either psychiatric illness or treatment
because sick patients are not their focus. There is no question
that basic studies are important, but their payoff is far from
immediate. Our concern is that the federal granting agencies
(particularly, the National Institute of Mental Health) and uni-
versity researchers have effectively abandoned clinical studies
of psychiatric medicines to the pharmaceutical industry. We will
review this unfortunate shift and suggest remedies.
Recent Progress
The past ten years, since this book’s first edition, has seen re-
markable, positive, changes in the public understanding of clini-
cal depression. A number of books, written for patients and
families, deal with mental illnesses, in particular, depression.
These books have been written by professional writers as well
as by sufferers from depression. The National Institute of Men-
tal Health has ongoing public-education programs. Public fig-
ures, notably Mike Wallace and Senator Chiles, have spoken
out about their illness, helping to destigmatize depression and
mental illness in general.
Patient support organizations broadened their agenda to
support private psychiatric research foundations. These sup-
port groups try to correct society’s views of mental illness as a
mere lack of will power, obtain parity on medical insurance,
stimulate research, and promote professional education.
Epilogue 183
Negative Trends
Despite these advances, negative trends have emerged. The

public spends billions on herbal “alternative” remedies and
“natural” substances in the belief that they are safer and more
effective than the high-tech medicines purveyed by the phar-
maceutical industry. This is fueled by suspicion of the industry’s
profit-driven motive, a distrust of technology, and a romantic
return to the good old days, when natural foods and remedies
were at hand—unfortunately, a nostalgic, unrealistic view of
the past experience with mental illness.
A movement for “animal rights” has ruthlessly exploited a
good-hearted, sympathetic devotion to pets, rather than the
more sensible concern for animal welfare, both human and non-
human.
To counter the stigmatizing beliefs that psychiatric illnesses
were psychological in nature, or “psychogenic,” the term “brain
disease” is now being used as a slogan—clearly more correct
than blaming bad mothering or offering other psychological
theories to explain biological problems. Unfortunately, HMOs
justify swift, inaccurate diagnosis and treatment based on a
superficial examination and have relied on this slogan. The in-
fluence of HMOs on medical practice cuts patient contact time
short, while paying less for care of mental illness. This is a dis-
incentive for skilled effort.
Surveys show that primary-care physicians regularly miss
clinical depression. When recognized, it is treated poorly. To
do a proper job of diagnosis and care takes time. This is under-
cut by the current rates set for coverage of mental illness. At-
tempts to achieve parity for mental illness insurance has, once
again, been defeated (2004).
The Continuing Lack of a

Knowledge Base for Medical Practice
Pharmacological treatment is the center of medical practice.

When illness drives you to a doctor, you expect medical sci-
ence to provide an exact diagnosis and to receive a beneficial
drug prescription. But when medication is prescribed, just what
does the doctor know?
184 Epilogue
Here are some practical questions for which we do not yet

have definitive answers:
• Patients often have many symptoms and impairments, or

even several illnesses, both medical problems and a psy-
chiatric illness. Which symptoms and impairments are
most or least likely to benefit from this treatment?
• Which drug is best?
• Which drug causes the least side effects?
• What is usually the most effective minimum dose?
• What is the maximum dose beyond which continuing to
push the dose yields no benefit?
• How fast should the doses be increased?
• How often should medication be given? Will once a day
work well?
• Which side effects indicate that treatment should be
stopped?
• How often should the patient be seen or talked with?
• Does the drug affect mental acuity, emotional responsive-
ness, creativity, sexuality, and other activities? If not now,
maybe later?
• When will benefit appear?
• How long do you wait before deciding this treatment will
not work?
• If the first treatment fails, what next?
• What if that fails?
• Does drug withdrawal cause problems?
• Will the drug be affected by other drugs?
• How does this treatment compare to other treatments,
with regard to benefit, speed of action, side effects, rela-
tive cost, and chances of relapse?
• Should treatments be combined? Which ones?
We could go on, but the message is plain. These questions

rarely have factual answers. Only a small part of psychiatric
practice is based on hard evidence. The FDA only insists that a
marketed drug outperform placebo and is safe during the short
term, but that is almost all that is known when the drug is mar-
keted and usually well after.
Epilogue 185
Laws and regulations decide who can market a product, or

where houses can be built, or assure safety in industry, or de-
crease pollution, and so forth. These public actions have enor-
mous, obvious, economic impacts and stir heated arguments.
However, as Marcia Angell, M.D., past editor of the presti-
gious New England Journal of Medicine, states, “The American
public seems to be extraordinarily attuned to threats to their
health. Issues such as asbestos, the possible cancer-causing ef-
fects of birth control pills, the multiple plagues supposedly pro-
duced by breast implants, the issue of drug recall by the FDA,
the safety of a new vaccination, caused endless discussion,
multiple newspaper headlines, hearings in Congress and not
infrequently billion-dollar class-action suits.”
Yet the sins of taking no action also gravely impact our lives,
but these pass unnoticed. A bad drug or a useless diagnostic
procedure produces a smaller effect on medical care than our
sparse knowledge of effective practice. The questions far out-
number the answers.
These deficiencies are not limited to psychiatry but are evi-
dent across all of medicine and surgery. There is a new slogan—
“evidence-based medicine”— which urges doctors to use tested
and proven treatments. This seems sensible, and is a step in the
right direction, but the underlying problem still exists. There
are many important clinical questions without evidence based
answers. And there is no financial, academic, or political incen-
tive to produce evidence that would answer these questions.
Demanding the knowledge required to improve care is not a
public demand—although it should be.
Drug Discovery
In psychiatry we are far from knowing the “pathologic mecha-

nism,” the underlying biological cause, of many mental ill-
nesses. So our working models of schizophrenia, bipolar
disorder, major depressive disorder, panic disorder, obsessive-
compulsive disorder, and the like, are incomplete. And yet many
claim that basic research will produce quick therapeutic ben-
efits and is required for progress. For instance, the Federation
186 Epilogue
of American Societies for Experimental Biology (FASEB) re-

leased a report titled “Federal Funding for Biomedical and Re-
lated Life Sciences Research FY 2000 Recommendation.”
Although FASEB’s recommendations are largely sensible, their
understanding of clinical research is that it “applies the under-
standing gained from basic research to problems of human
health.” For psychiatry this is premature, because of our insuf-
ficient knowledge of how the brain works and why it goes awry.
Even for general medicine, the case for the progression from
basic scientific knowledge to clinical usefulness is not direct.
To use just one example, the recognition of Viagra’s erectile
benefit was a serendipitous observation made during the in-
vestigation of Viagra as a possible anti-hypertensive drug. Pa-
tients reported the peculiar “side effect” of enhanced erections.
Once the clinical discovery is made, basic research is required
to understand how it works. The problematic reality remains
that every major psychotropic drug discovery has been due to
clinical observations of unexpected benefits. So an exclusive fo-
cus on basic science, in the hope of new treatments, is misguided.
The Process of FDA Medication Review:

The Lack of Postmarketing Surveillance
Since the activities of the Food and Drug Administration (FDA)

are often misunderstood, we briefly describe how it works.
Many people think the job of the FDA is to promote the public
health by bringing out new beneficial drugs. But their job is
actually to prevent the release of unsafe or ineffective drugs.
They are a regulatory agency, whose job is to appropriately say
“No”; it is not their job to find or promote useful treatments.
The law says that medications must be proved safe and ef-
fective before marketing is allowed. This has led to our cur-
rent system of FDA drug approval (note this law does not
apply to psychotherapy or surgery). After a medication has
gone through animal studies for safety and possible useful-
ness, there follows human safety studies, usually in healthy
subjects but sometimes, as with anticancer drugs, in patients.
This is referred to as Phase I.
Epilogue 187
This is followed by openly treating patients so as to observe

possible treatment benefits (Phase II). If Phase II is promising,
elaborate, usually multisite, double-blind, placebo-controlled,
randomized studies of thousands of patients are done (Phase
III). Phase III makes sure that early promising effects are actu-
ally real.
Once completed, reams of research data are shipped to the
FDA for a detailed review that may go on for years. Finally, the
FDA may agree that the material is valid enough to be pre-
sented to an Advisory Committee. The independent experts on
this committee review the various summaries and debate
whether the drug is safe and effective, and therefore
“approvable,” or requires more work, or should be rejected.
Their decision is not binding on the FDA.
However, even if the FDA accepts approvability, 10 to 15
years after the first human use, it is still not ready for market-
ing. The problem is writing the “package insert,” which accom-
panies every bottle of medication and sets the limits for
advertising. Its language will enter the ubiquitous PDR (Physi-
cians’ Desk Reference) as warnings, contraindications, and side
effects. The package insert must be negotiated between the FDA
and the company. This directly affects profitability.
A concerned FDA may demand an insert, rimmed by a black
box, in which warnings are highlighted. Such a black box is
considered a sales killer by industry. Such discussions usually
last months. The company may actually discard a drug as prob-
ably unprofitable if a “black box” is required.
The FDA can influence medical caution before marketing.
But once a drug is marketed, there is no standard system for
postmarketing surveillance—that is, finding out how those who
receive the drug are benefited or harmed. Doctors are not
obliged to report possible side effects to the FDA, although some
do. But even if they do, there is no system to find out if the
symptoms that occur after taking a medication are actually due
to the medication, or to an interaction with another drug, or to
an illness that has nothing to do with the medication, or maybe
to unusual allergies of a patient, or something they ate, and so
on. Therefore, this unsystematic information about postmarket-
ing side effects includes a flood of misinformation; all added to
188 Epilogue
the package insert, thus protecting the company from suits

claiming patients were not informed of possible risks. How-
ever, this drastically reduces the worth of the PDR warnings,
while they scare the hell out of patients.
On occasion, rare dangerous effects such as liver failure or
blood abnormalities are reported. The FDA, or the company,
may then decide to withdraw the drug from the market imme-
diately. This judgment is usually hasty and political. The phar-
maceutical industry is an easy target for accusations of
negligence and profiteering. And the FDA is damned if it does
and damned if it doesn’t: that is, for releasing dangerous drugs
into the market but also for taking too long to release promis-
ing drugs. Thus, the FDA leans over backward to avoid ap-
proving any possibly dangerous drug, which slows down the
release of all drugs, but also has a hair-trigger response leading
to drug withdrawal. The pharmaceutical industry, spooked by
class-action suits, such as the one that bankrupted the asbestos
industry, often withdraws products even before the FDA de-
mands it.
This is not a rational system. A proper system of computer-
ized postmarketing surveillance through prescription registra-
tions and symptomatic reporting would let scientific monitors
know how many patients are exposed to particular medications,
if the side-effect rates differ from the usual, and determine the
kind of patient who is at risk for severe side effects. This would
be a complicated, difficult undertaking. For instance, it will be
hard to tell if a drug given to very sick people is helping or harm-
ing. Nonetheless, it is a feasible goal. But nobody lobbies for it.
Some drugs have occasional serious side effects, but are still
uniquely useful. For instance, clozapine is an invaluable anti-
psychotic that can work when no other drug does. However,
on rare occasions, it can cause a blood disease that can be fatal.
Thus, the FDA required a weekly blood test that markedly de-
creases this risk. Since no other drug approaches clozapine for
effectiveness in difficult cases and since chronic schizophrenia
is so serious, the FDA allows marketing, but requires the sys-
tematic blood testing.
A similar program could have been developed for nomifen-
sine (considered a uniquely valuable antidepressant) which also
Epilogue 189
can cause a blood disorder. However, given the availability of

other antidepressants, coupled with a lack of concern for the
subgroup of patients who need that particular drug, no at-
tempt was made to keep this valuable drug available through
proper monitoring. The company withdrew it, and it is no
longer available.
Pharmaceutical companies are reluctant to search for evi-
dence that a particular drug works best for a subgroup of pa-
tients, such as those with treatment-resistant depression. If there
are no specific indications declaring when an agent is useful, a
“broad” spectrum of action can be claimed. For those who re-
spond poorly to an initial treatment, finding out whether one
drug works better than another is important, but again, avoided
by the pharmaceutical industry, perhaps in fear of discovering
that their drug is worse than the competition. Thus, competi-
tive economic forces within the industry are strong incentives
to avoid developing such clinically vital information.
The Special Case of Children and Adolescents
Before marketing, the FDA must approve a medication’s safety

and efficacy for a particular disorder. However, it is a matter of
medical judgment whether a marketed drug should also be used
for similar conditions. This is referred to as “off-label” prescrib-
ing and is very common.
Children and adolescent depression have not been studied
extensively. Therefore, SSRI antidepressants shown useful in
adults have been prescribed for children.
To date, only Prozac has been shown safe and effective in
child and adolescent depression. There has been much concern
that some firms have evidence that their drugs are actually in-
effective but have not made this known.
There is even more concern that these drugs may actually
cause suicidal attempts, although no actual suicides have oc-
curred in the treatment studies.
This is a difficult situation, since it is not clear, as yet, whether
the reported negative effects are due to the drug or to the ill-
ness itself.
190 Epilogue
Therefore, caution dictates that the use of antidepressants in

children be restricted to those where medication is clearly needed.
What constitutes a serious depression? A child or adolescent
is seriously depressed when he or she has multiple severe symp-
toms of depression, is seriously impaired in functioning, ex-
presses thoughts such as the lack of meaning or purpose in life,
or talks about death or suicide. Serious impairment in func-
tioning refers to a marked loss of interest in activities the youth
previously enjoyed, withdrawal from friends and family, and
deterioration of performance in school. Because self-harm is a
serious risk and because antidepressants may decrease the risk
of suicide, the cautious use of the most effective treatment avail-
able is one in which the benefits exceed the risks.
Also, any treatment for such children (not just by drugs but
also by psychotherapy) requires vigilant monitoring of the
child’s condition. Weekly reviews are often necessary. It is bad
treatment to diagnose depression, prescribe medication, and
schedule the patient to be seen in a month. Parents must be
educated that if things do not go well the doctor must be quickly
informed.
Fostering Serendipity
How can serendipitous observations of unexpected clinical

benefits be fostered? An environment in which patients are well
known to their doctors and easily observed for a substantial
time makes the detection of unexpected benefits much more
likely. By studying chronically hospitalized patients, anti-
psychotics, antidepressants, and antipanic agents were discov-
ered. However, in the subtler, inherently fluctuating disorders
that are common in outpatients, observing possible benefits is
much less reliable. Reports of improvement may be mislead-
ing since the improvement may have occurred in spite of the
treatment. For instance, sexual inhibition is often caused by
selective serotonin reuptake inhibitors (SSRIs). This common
effect was not initially noted by industry. After it was clinically
obvious, many anecdotes of supposedly beneficial antidotes
have been reported. Nonetheless, to this day, no large-scale case
series or controlled treatment study has examined how to coun-
Epilogue 191
teract this important, treatment-impairing side effect. Perhaps

the pharmaceutical industry avoids such studies because this
openly admits the real importance of this side effect, leading to
negative repercussions on marketing and profit. There are few
academic rewards for doing such studies. Therefore, our igno-
rance persists.
The Current State of Psychiatry
An unblinking look at the state of psychiatry must recognize

the problematic facts. Psychiatric diagnosis is still at a descrip-
tive level because objective, specific, diagnostic tests have not
been discovered. Therefore, similar conditions that actually have
different causes and treatment responses are lumped together.
Theories about the causes of psychiatric illnesses are poorly
supported and have a bad historical record. Few have survived
rigorous tests. The conventional wisdom about how both the
psychotherapies and the pharmacotherapies work is superfi-
cial. Therefore, attempting to deduce from theories how to im-
prove treatment usually doesn’t work.
Research has demolished some simplistic notions, but this
has not translated into treatments. The hopes that genetic re-
search will allow laboratory diagnoses of psychiatric diseases
have floundered amid the complexity of genetic findings that
reveal just how much we don’t know. Even though the exact
simple genetic mechanism for Huntington’s disease was iso-
lated over 15 years ago, and although the damaged protein pro-
duced by this defective gene is known, translation into a
therapeutic intervention has not yet occurred. This is probably
because of the complex, and still largely unknown, cascade of
events that take place between gene, gene product, and clinical
manifestations in the body and brain. This remains one of the
few cases, however, where diagnosis has been made objective,
through the use of genetic screening.
Because the major treatment advances in psychiatry have
been serendipitous, one would think our scientific leadership
would focus on developing clinical contexts that foster seren-
dipity. But this is not the case. “Chance and the prepared mind”
192 Epilogue
require the clinical opportunity for discovery, but the contact

of experienced clinicians with possible new drugs is steadily
shrinking.
The Need to Focus on Illness
If we really understood normal psychological and brain func-

tions, then understanding psychiatric illness might be straight-
forward. Attempting to evaluate and treat things that have gone
wrong, without first understanding normal functioning seems
misguided.
However, the human organism, and particularly the brain,
is fantastically complex. The past half century has given us a
mind-boggling glimpse of the complexities that remain to be
discovered. Every day a new discovery reveals just how much
we still need to understand.
Fortunately, medical advances have not depended on first
correctly understanding normal functioning, but rather focused
on treating illness. Treatments that somehow succeed, highlight
what went wrong. This allows the discovery of further treat-
ments that somehow repair or compensate for the still poorly
understood dysfunctions.
In medicine, until very recently, the sciences benefited from
clinical discoveries rather than the other way around. The de-
velopment of vaccines and antibiotics fostered the field of im-
munology. The treatment of scurvy, pellagra, and beriberi led
to the discovery of the vitamins that played a role in these dis-
eases, which in turn taught us how the enzymes, the basic bio-
logical catalysts, worked. The development of antipsychotics,
antidepressants, and anti-anxiety drugs fostered the neuro-
sciences, which may eventually in turn discover the underly-
ing cause of mental illnesses.
It follows that in psychiatry, given our inadequate grasp of
what goes wrong and why, that a major research focus should be
the detailed, imaginative study of novel therapies on difficult-
to-treat illnesses. Focusing on the processes that underlie effec-
tive treatments of psychiatric illness suggests testable hypotheses
about what went wrong. That is a good bet for advancing both
basic knowledge of disease mechanisms and clinically useful
Epilogue 193
understanding. Can we once again focus on the impact of psy-

chiatric treatment and the observation of surprising clinical
benefits? This requires radical changes in both drug develop-
ment and clinical care. It will not happen unless the public,
sparked by patient support groups, demand it.
Treatment-Resistant Depression
Carrying out treatment studies in the usual community clinic

is simply too difficult. Clinicians object to patients being ran-
domly assigned to treatments because they believe they already
know what should be done. Scientifically untrained personnel
yield unreliable, misleading measurements. Yet one must evalu-
ate and provide improved treatment for patients with difficult,
complicated illnesses. The hope was that the discovery of po-
tent new medications, combined with randomized, placebo-
controlled, double-blind trials, would create evidence-based
comparisons of different treatments. This has not occurred. If
the first treatment fails, hardly anything is known about what
the second treatment should be.
One solution would be to develop standing, research-
oriented clinics and day hospitals to provide systematic collec-
tion of data.
Absence of Sound Psychotherapy Research
There is no industry, comparable to the pharmaceutical indus-

try, to support the study of psychotherapy. The American Psy-
chological Association (which used to be research focused) has
turned into a psychotherapists’ guild. However, they also ac-
tively lobby for the right to prescribe medications, with a re-
cent success in New Mexico. This organization’s domination
by privately practicing psychotherapists, who claim promis-
ing results for many of their therapies, reached the point that
many scientist members split off to form the American Psycho-
logical Society in 1988. However, this new group does not fo-
cus on evaluation of treatment.
Studies of psychotherapy benefits rarely take into consider-
ation the effects of suggestion, family support, or the passage
194 Epilogue
of time. Comparisons of different psychotherapies that suppos-

edly work by entirely different mechanisms rarely show one
more effective than another.
Competing claims about the relative value of pharmaco-
therapy and psychotherapy, with regard to cost, speed of onset
of effect, acceptability, degree of benefit, ability to maintain ef-
fects over time, and so forth, are almost never based on actual
collaborative trials between experts with differing backgrounds.
The rare collaborative expert comparative trial is almost never
repeated. Nonetheless, the popular press often seizes on sur-
prising, undocumented claims for psychotherapeutic benefit.
Public Pressure
The general public thinks it knows too little to even express an

opinion about the goals and methods of medical research. But it
was public pressure, sparked by the philanthropist Mary Lasker
and the psychopharmacologist Nathan Kline, that led Congress
to force the National Institute of Mental Health (over the objec-
tions of its director) to develop the Psychopharmacology Research
Service. A system for funding independent academic clinical
psychopharmacological studies was thus started. Unfortunately,
this effort lapsed when NIMH effectively abdicated support of
such clinical studies to the pharmaceutical industry.
Patients can affect government and industry policies, if they
clearly understand what will benefit them and are well orga-
nized. The well-organized, public relations savvy success of the
AIDS activists and the National Organization of Rare Diseases
convinced Congress that federal incentives should spur treat-
ment development for their constituencies. Realistically improv-
ing medical practice will also require political organization and
public pressure.
Development of a Proactive Federal

Medical Practice Improvement Agency
There is no federal agency primarily charged with improving

the public health by developing medications or monitoring
practice. The FDA is regulatory, not proactive. Their job is to
Epilogue 195
say, “No,” not to search for opportunities to say, “Yes.” The

National Institute of Health primarily supports research in the
basic sciences rather than treatment and practice issues.
A National Board of Medical Experts should be part of a pro-
active agency. Pharmacological experts would review undevel-
oped opportunities, including medications studied abroad.
Potentially useful drugs with expired patents provide no finan-
cial incentive for companies to invest in establishing new uses
(e.g., lithium as an add-on for refractory depression). There-
fore, this federal agency should offer the cheap financial incen-
tive of increasing the period of marketing exclusivity, if the
potentially useful drugs are found to satisfy FDA requirements
for safety and efficacy. Other incentives are needed for promis-
ing compounds “sitting on the shelf” because they are thought
to be unprofitable. The same applies to likely new uses for
marketed drugs that the drug industry does not pursue because
of insufficient projected profitability.
In all these cases there is no actual increased federal expen-
diture on research. Rather, industry is given new incentives, if
they accomplish specific goals that public health experts agree
are worthwhile.
This new proactive agency should develop joint NIMH/
industry/FDA collaborative programs on clinical trial meth-
ods. The precedent for such cooperation comes from the devel-
opment of drugs that requires improvement in assessment
methods (e.g., Alzheimer’s disease and obsessive-compulsive
disorder).
The largest sets of data relevant to improving clinical trials
are owned by industry and protected by law, even if used to
gain FDA approval. For regulatory approval, the pharmaceuti-
cal industry naturally presents the most favorable analyses.
They rarely make raw data available to independent research-
ers; therefore, potentially informative independent analyses
cannot be done. There is almost no opportunity to indepen-
dently compare drugs, except through weak techniques applied
to data summaries.
We believe that the data files that support all the analyses
published in medical studies should be made available, on
publication, by placing the underlying data on the Web. After
196 Epilogue
all, publication of data summaries affirms that the supporting

data is real and correctly analyzed. Independent, critical reanaly-
sis would amplify peer review. The current peer review system
does not require, or even allow, the reanalysis of primary data.
Financial incentives for investigators and journals to carry out
such analyses should be provided by the proactive agency.
Also, nobody is under any obligation to publish a study say-
ing that a drug is useless. This can be very valuable knowledge
but can also be against the economic interest of the sponsors.
There is a peculiar ethical problem here. Patients volunteer to
undergo the risks and discomforts of a clinical trial, so as to
increase medical knowledge. Shouldn’t informed consent in-
clude the fact that they may be wasting their time or shouldn’t
the Institutional Review Boards require that the sponsor guar-
antee that detailed publication will be forthcoming? Such ethi-
cal issues are largely ignored.
Clinical Research Centers
This new Federal Medical Practice Improvement Agency could

establish a network of Clinical Treatment Research Centers of
excellence. These centers would supervise multisite, research-
oriented, model clinics and day hospitals, whose job would be
to expertly evaluate patients who have not responded to usual
clinical care. Careful, reliably documented studies of treatment
processes and outcomes can develop outcome norms for these
groups, defined by diagnosis, economic status, treatment his-
tory, and comorbidity.
All research is, to some degree, a gamble on an unknown
future. Treating and studying many well-delineated patients,
some who may also have medical, psychiatric, and substance-
abuse conditions, would define expectable treatment outcomes.
Therefore, if a new approach looks better than expected, this
provides a rational basis for undertaking the expenses and dif-
ficulties of a proper clinical trial.
Public Involvement
A regular public conference program on medication develop-

ment should be started. Our society has made only piecemeal
Epilogue 197
adjustments to the flood of extraordinary pharmacological ad-

vances. Given recent developments in molecular and genetic
biology, enormous strides are possible. However, without a
well-formulated, continued national discussion and debate con-
cerning how to foster and regulate these advances, the current
period of public misinformation and regulatory chaos will get
even worse. The current debate over whether estrogens should
be used for menopausal symptoms is a forerunner of even more
heated arguments.
Developing a proactive program for drug development and
monitoring is essential. Many of our suggestions are contro-
versial. Some may be wrong. Our intention is to stimulate open
discussions of thorny issues by informing the public how they
are being short-changed with regard to achievable medical
advances. The democratic political process has a chance to
work constructively only if correct information is available
and debated.
Index
activating drugs, 137 American Psychological Society,

ADHD (attention-deficit hyper- 193
activity disorder), 72, 181 amitriptyline (Elavil), 95, 137
adolescents. See children and amnesia, anterograde, 148. See
adolescents also memory effects
adoption, 87–88 amphetamines, 106, 107, 134
adrenalin, 95–96, 152 anemia, 80, 90
African Americans and depres- anesthesia and ECT, 113
sion, 70 Angell, Marcia, 185
agoraphobia, 153, 157, 160–61, anger, 32–33, 58, 91, 173
163 anhedonia, 15, 100
agranulocytosis (blood disease), animal rights, 183, 186
146 anticonvulsant drugs, 81, 142–
Albers, J., 127 45
alcohol, 30, 52–53, 71, 74, 84 antidepressant medication, 7,
allergies, 97 38–39, 76, 100, 101–12, 132–
alprazolam (Xanax), 147, 159, 38; chemical function of,
167 95–96; for children and ado-
Ambien (zolpidem), 106, 148 lescents, 72, 134–35, 189–90;
American Cancer Society, 3–4 in combination, 109, 110, 129,
American Psychiatric Associa- 140–46, 177; dependence on,
tion, 4, 174 107, 110, 147; effectiveness
American Psychological Asso- of, 101, 106–12, 128–29; first-
ciation, 193 generation, 137–38; and
199

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Understanding Depression:

A Complete Guide to Its

Donald F. Klein, M.D.

OXFORD UNIVERSITY PRESS

2. Symptoms of Mood Disorders: Recognizing Biological

3. What Happens to the Depressive or Manic-Depressive

DEPRESSION MAY be a normal human emotion—a

1. To explain what biological depression is and to clarify the

2. To give the reader brief self-screening tests that can help to

Let us elaborate on these points:

1. Biological depression is common—in fact, depression and

If there were a physical disease that manifested itself in

would plead and demand that this suffering be eased.

Depressive illness is common, painful, and dangerous, but

themselves but to teach them to watch for suggestive symptoms—

availability of the diagnostic manual has stimulated the teach-

development for the health of the public would be a move to-

In urging family participation, we are not referring to

medical evaluation and medical treatment. The purpose of this

The Question of Names

THE NAMES of the “mood disorders” have changed

as delusions (false beliefs) and hallucinations. We now realize

tients we have treated. In elaborating on the description of de-

Self-Rating Scale for Depression

Have either of the following symptoms been present nearly

A.1. Have you been sad, blue, or “down in the dumps”?

If either A.1. or A.2. is true, continue. If not, you probably do

1. A poor appetite or overeating? No Yes

3. Oversleeping? (Going to bed earlier than

4. Do you have low energy, fatigue, or

5. Are you less active or talkative than

6. Do you avoid the company of other

7. Do you lose interest or enjoyment in

8. Do you fail to experience pleasure

9. Do you have feelings of inadequacy or

10. Are you less efficient or do you accomplish

11. Do you feel less able to cope with the

12. Do you find that your concentration is

should consult a qualified physician. Even if you have only two

social life have been substantially affected, a checkup is highly

Recurrent Problems in Patients’ Illnesses

The symptoms of sadness and loss of interest in life are two

eating and sex. People also look forward to family gatherings,

The cases given derive from actual case histories, with

5 Jill Jason, a busy young housewife and mother, found

Jill’s mood was particularly bad in the morning. Sometimes

5 Mary Malloy was a vivacious young receptionist who or-

Mary spent a lot of time quietly in bed. However, when

Surprisingly, when she did agree to go out, she seemed to

Finally, like Jill Jason, Mary was persuaded to go to a resort

5 Milton Meyer was a successful surgeon in his forties who

playing in his amateur quartet, and hired someone to take

When the cousins were in their early thirties, their fathers,

Despite their torment, both women rose to the occasion and

After some three months, Sally’s emotional life had pretty

Most of the time people have a feeling of zest, of get-up-and-

5 Mary Malloy expected to hear from her remaining boy-

now she felt physically incapable of moving. She crawled

5 Sally Harris had resumed her meaningful 60-hour work