CNS Drugs (2013) 27:789–797

DOI 10.1007/s40263-013-0097-3

LEADING ARTICLE

Current Place of Monoamine Oxidase Inhibitors in the Treatment

of Depression
Kenneth I. Shulman • Nathan Herrmann •

Scott E. Walker

Published online: 10 August 2013

Ó Springer International Publishing Switzerland 2013

Abstract This paper reviews the discovery and history of depression but have not replaced the irreversible MAOIs
the use of irreversible monoamine oxidase (MAO) inhibi- for the specific sub-types of depression for which they are
tors (MAOIs) such as phenelzine, tranylcypromine and now recommended in most consensus guidelines and
isocarboxazid, as well as the second generation selective treatment algorithms.
and reversible MAOIs such as the MAO-A inhibitor, The pharmacology, drug interactions and dietary rec-
moclobemide and the MAO-B inhibitor, selegiline. Data ommendations associated with the use of MAOIs are
for review were identified from a literature search of reviewed. With the appropriate dietary restrictions and
OvidSP Medline and PsycInfo performed in July 2012, attention to potential drug interactions with serotonin and
using the subject terms and keywords of ‘monoamine noradrenaline agents this class of drugs can be used
oxidase inhibitors’, ‘major depression’, ‘depressive disor- effectively and safely. The MAOIs still represent an
der’ and ‘depression (emotion)’. The search was limited to important element in our therapeutic armamentarium.
papers published in the English language and from 2007 Despite recommendations by opinion leaders and consen-
onward only. sus guidelines for the use of MAOIs in specific sub-types of
Irreversible MAOIs have the potential to treat the most depression, the prescription rate of MAOIs is far less than
challenging mood disorder patients including those with expected and is decreasing. The ‘‘bad reputation’’ and the
treatment-resistant depression, atypical depression and lack of industry support for this class of agents (especially
bipolar depression. Unfortunately, the use of irreversible the irreversible MAOIs) must be overcome in order to
MAOIs has been declining sharply due to lack of market- continue to provide a potentially useful treatment for a very
ing and the excessive fears of clinicians. Moreover, few vulnerable yet substantial sub-population of mood disorder
clinicians now have any experience, let alone comfort, in patients.
prescribing this class of antidepressants. The newer MAOIs
are available as another option for the treatment of major
1 Historical Background of Irreversible Monoamine
Oxidase Inhibitors (MAOIs)

As in many discoveries in psychiatry, the use of irre-

K. I. Shulman (&)
N. Herrmann versible monoamine oxidase (MAO) inhibitors (MAOIs)
Professor, Department of Psychiatry, Faculty of Medicine, began by serendipity. In the early 1950s, the antituber-
University of Toronto, Sunnybrook Health Sciences Centre, cular agent iproniazid—a derivative of the hydrazine
2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
e-mail: [email protected] compound isocarboxazid—was found to have antidepres-
sant effects in tuberculosis patients who suffered from
S. E. Walker depression [1]. Following this discovery, the MAOIs were
Associate Professor, Faculty of Pharmacy, University used as the first effective antidepressants and by 1957
of Toronto, Director of Pharmacy and Division of Clinical
Pharmacology, Sunnybrook Health Sciences Centre, Nathan Kline published the first report on the neuropsy-
2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada chiatric experiences with iproniazid calling it a ‘‘psychic
790 K. I. Shulman et al.

energizer’’. Within a year of that report more than permanently deactivate it, and the enzyme function is not
400,000 depressed patients were treated with this drug restored until the enzyme is replaced. Newer MAOIs,
marketed as Marsilid [2]. such as moclobemide, are reversible, meaning that when
Shortly after iproniazid was discovered to have antide- the inhibitor dissociates from the enzyme, activity is
pressant properties it was also found to inhibit the enzyme restored.
MAO, which is involved in the catabolism of serotonin, MAOIs are also defined by their selectivity. Some
noradrenaline and dopamine [1]. In association with the inhibitors selectivity inhibit isozyme A (moclobemide),
discovery of tricyclic antidepressants (TCAs), this led to others selectively inhibit MAO-B (pargyline and selegi-
the formulation of the monoamine theory of depression. line) and some are non-selective (phenelzine, tranylcyp-
Moreover, the discovery of an ‘‘antidepressant drug’’ such romine), inhibiting both A and B. However, selectivity is
as iproniazid had a profound effect on the overall attitude often concentration dependent and selegiline is truly only
towards clinically significant depression by emphasizing its selective at low doses, but is non-selective at high doses or
underpinnings as a ‘‘chemical imbalance’’ [2]. Over sub- concentrations [9].
sequent decades, antidepressants with a wide variety of
monoamine-based mechanisms of action were developed.
Iproniazid was eventually removed from the American 3 Tyramine Reaction and Hypertensive Crisis
market because of hepatotoxicity, but was followed by the
discovery of more potent inhibitors of MAO, which were Administration of tyramine results in the displacement
more effective antidepressants including phenelzine (Nar- of noradrenaline from neuronal storage vesicles. This
dil), isocarboxazid (Marplan) as well as the non-hydrazine produces vasoconstriction and an increased heart rate
derivative tranylcypromine (Parnate). In the 1960s and and blood pressure. A tyramine pressor response, which
1970s, the MAOIs were commonly combined with neuro- is defined as an increase in systolic blood pressure of
leptic agents. Once such combination was a drug known as 30 mmHg or more, varies between MAOIs and the
Parstelin, a combination of trifluoperazine (Stelazine) and route of administration (intravenous (IV) vs. oral).
tranylcypromine (Parnate). Now, such combination drugs Bieck [10] demonstrated that the sensitivity to tyramine
are no longer used. was always larger after oral tyramine relative to IV and
MAOIs have continued to be prescribed albeit in increased with increasing doses of phenelzine. Com-
markedly decreasing frequency as their use has been dra- pared to the control treatment, blood pressure sensitivity
matically influenced by safety concerns about the tyramine to IV tyramine increased 2.6-fold during phenelzine
reaction and hypertensive crisis (see below) as well as the (60 mg/day), whereas sensitivity to oral tyramine
fact that they are not promoted by any major pharmaceu- increased from fourfold following 30 mg/day of phe-
tical company. Moreover, residents are not exposed to the nelzine to 15.7-fold following 60 mg/day of phenelzine.
use of MAOIs during training. This is due largely to an increase in tyramine bio-
availability because of MAO-A inhibition in both the
liver and intestine.
2 Pharmacology of MAOIs, Including Irreversible Non-selective MAOIs generally elicit a greater tyramine
and Reversible MAOIs pressor response than selective MAOIs. While the
peripheral distribution of MAO enzyme would suggest a
MAO catalyzes the oxidative deamination of monoamines. greater blood pressure response from MAO B inhibition,
In humans there are two types of MAO: MAO-A and dose response can confound this interpretation. Neverthe-
MAO-B [3]. Serotonin, melatonin, noradrenaline, and less, Tiller et al. [11] have demonstrated a doubling of the
adrenaline are primarily deaminated by MAO-A while sensitivity (equivalent pressor response with half the
phenethylamine and benzylamine are deaminated by tyramine dose) with moclobemide, a selective MAO-A
MAO-B. Both forms break down dopamine, tyramine, and inhibitor. This can be compared to the work of Sunderland
tryptamine equally [4]. Distribution of MAO-A and B [12] who demonstrated a 3.7-fold increase in sensitivity
varies throughout the body. In most peripheral tissues, with a 10 mg per day dose of selegiline which was
MAO isozyme activity is predominately MAO-A [5–7], enhanced to a 22-fold increase at 60 mg/day. This is
whereas, in brain MAO-B activity predominates [8]. similar to the sensitivity observed with the non-selective
MAOIs inhibit the deamination or metabolism of the tranylcypromine and serves to demonstrate that the selec-
neurotransmitters. The early MAOIs inhibited MAO tive nature of MAO-B inhibition of selegiline is lost at
irreversibly. When they interact with MAO, they higher doses [12].
MAOIs in the Treatment of Depression 791

4 Drug Interactions with MAOIs 5 MAOI Diets

While many drug–drug interactions occur through inhibi- Since 1911, it has been known that tyramine which is
tion of cytochrome P450, the most serious interactions with derived from the amino acid tyrosine, (meaning cheese in
MAOIs occur through pharmacologic mechanisms related Greek) had the potential to increase blood pressure. How-
to the inhibition of MAO. Since serotonin is primarily ever, it was in the 1960s when Barry Blackwell [19] pub-
deaminated by MAO-A, any drug that works as a serotonin lished a series of case reports in which hypertensive crises
reuptake inhibitor (SRI) can produce serotonin syndrome, a were precipitated by the ingestion of cheese with MAOIs.
dangerous and potentially fatal interaction when combined This alarming discovery at a time of increased ‘‘medical
with an MAOI. SRIs including sertraline, fluoxetine, par- legal sensitivity’’ led to a dramatic decline in the use of
oxetine, fluvoxamine, citalopram, escitalopram, TCAs such MAOIs and also to the development of over inclusive
as clomipramine or imipramine as well as serotonin— dietary restrictions. In an international survey by Sullivan
noradrenaline reuptake inhibitors (SNRIs) like venlafaxine and Shulman [20] as many as 70 different food items were
and duloxetine can produce excessive intra-synaptic sero- listed on a variety of MAOI diets.
tonin when co-administered with a MAOI [13]. This dual Over the last 2 decades, Shulman and colleagues [21]
mechanism of inhibition (inhibition of serotonin metabo- conducted a series of careful tyramine analyses in con-
lism and inhibition of reuptake) can lead to clonus, hyper- junction with a thorough review of case reports and pro-
reflexia, hyperthermia and agitation. The onset of toxicity duced a much simpler MAOI diet (see the Appendix, which
is usually rapid and begins when the second drug is outlines the Sunnybrook MAOI diet). This diet is an
absorbed and reaches effective concentrations. Symptoms attempt to balance patient compliance with safety concerns
subside when one of the drugs has been eliminated. For the and in our experience has proven to be useful and practical.
SRI or a reversible MAOI this will take about 5 half-lives This diet restricts only a very few significant food items
of the drug. For most drugs this will be \2 weeks [14]. including aged cheeses, aged meats, concentrated yeast
However, for fluoxetine, since the metabolite, norfluoxe- extracts (marmite), draft beer, sauerkraut, and soy sauces.
tine has a half-life of at least 2 weeks [15], the washout
period should be much longer.
Some opioid analgesics such as meperidine, tramadol, 6 Irreversible MAOIs
methadone and dextromethorphan appear to be weak SRIs
and have all been reported to cause serotonin syndrome 6.1 Efficacy and Effectiveness
with MAOIs [13]. Even the selective MAO-B inhibitor,
selegiline has been reported to cause serotonin syndrome Krishnan [22] has reviewed the evidence for the efficacy
[16]. While this has been reported in a patient receiving and effectiveness of irreversible MAOIs for a variety of
only 5-mg of selegiline twice per day [16], pharmacology mood conditions. Overall, studies have shown that in an
would predict that this is more likely to occur when the outpatient population suffering from depression, those
selective nature of selegiline is lost at higher doses. treated with MAOIs had a response rate between 50 and
MAOIs, interaction with indirect acting sympathomi- 70 %, similar to that of TCA. The three most commonly
metic amines is perhaps the most likely to occur because of used MAOIs namely tranylcypromine, phenelzine and
the prevalence of pseudoephedrine and phenylephrine in isocarboxazid were found to be equally effective in
‘over-the-counter (OTC)’ cough and cold—decongestant treating major depression [23]. Georgotas et al. [24],
products. Pseudoephedrine and phenylephrine displace or found that elderly patients with depression treated with
release adrenaline from the presynaptic nerve. This results in phenelzine did significantly better in terms of recurrence
an increase in blood pressure, reported to more than double of mood disorder compared to those elderly patients
the pressure response of phenylephrine alone when com- treated with the TCA nortriptyline or compared to pla-
bined with phenelzine or tranylcypromine [17]. Pseudoe- cebo. This effect may be related to the increase in MAO
phedrine has been replaced with phenylephrine in many observed in older adults [25] and in major depression
decongestant products in North America. However, since [26].
both are equally capable of increasing blood pressure, Atypical depression is defined by mood reactivity as
patients should be advised to avoid both pseudoephedrine well as at least two of the following symptoms: hyper-
and phenylephrine containing decongestant products. The phagia or weight gain, increased sleep, subjective feeling
commonest nasal decongestant which is not an indi- of leaden paralysis, and rejection hypersensitivity [27, 28].
rect sympathomimetic amine is oxymetazoline. This adren- It has been estimated that some 30 % of depressives may
ergic alpha 2 agonist can be used safely with MAOIs [18]. meet these criteria [29]. In this subtype of depression,
792 K. I. Shulman et al.

phenelzine was found to be superior to the TCA amitrip- treatment of depression includes the use of ’MAOIs as a
tyline. Henkel et al. [30], using meta-analysis found a mean step four of five steps, just ahead of electroconvulsive
effect size of 0.45 favouring MAOIs over placebo and also therapy [39].
found a more modest effect size favouring MAOIs over Nolen et al. [40] reported a failed trial of lamotrigine vs
TCAs. In a double-blind randomized controlled trial of tranylcypromine in the treatment of refractory bipolar
phenelzine, imipramine, and placebo, phenelzine, with a depression and highlighted some of the methodological
response rate of 71 %, was clearly superior to placebo challenges in recruiting patients to such a trial. They still
(28 %) and was also significantly better than imipramine concluded that there was a role for tranylcypromine in the
with a response rate of 50 % [27]. treatment of refractory bipolar depression.
In studies of TCA resistant patients, approximately Stewart [41] reviewed the treatment of atypical
50 % responded to MAOIs [31, 32]. This response rate depression and concluded in his analysis that despite some
compared to TCAs was even more pronounced in atypical methodological concerns, efficacy reports seemed to favour
depression. Krishnan [22] concluded that MAOIs are MAOIs followed by TCAs.
probably the treatment of choice for later staged treatment In the STAR*D trial [42], MAOIs were used as a level
resistant depression and may be preferentially helpful with four treatment in refractory depression [43]. Not surpris-
specific subtypes of depression including atypical depres- ingly, in the context of the poor overall results of the
sion, anergic bipolar depression and anxious/phobic asso- STAR*D trial, the effectiveness of the MAOIs was very
ciated depression. In a recent prospective study of modest indeed. Treatment with a MAOI yielded a remis-
treatment resistant unipolar depressed patients discharged sion rate of 6.9 % and a response rate of 12.1 % in those
from a tertiary unit in the UK, Fekadu et al. [33] found a who had not achieved remission in three prior trials of
positive association between treatment with an MAOI and medication. However, methodological challenges make it
remission at discharge as well as remission at final out- difficult to interpret this finding. The average dose of
come. They call for renewed attention to the potential role tranylcypromine was low at 36.9 mg/day and maximum
of MAOIs in this especially vulnerable sub-population of dose was 60 mg. Nolen et al. [44] note that most trials of
mood disorder patients. To further emphasize the potential refractory depression used dosages of tranylcypromine up
role of MAOIs in refractory depression, a recent letter from to 100 mg or even higher.
Hamani et al. [34], reports on a patient who had an
incomplete response to the experimental treatment of deep 6.2 Safety and Prescription Patterns
brain stimulation. When the tranylcypromine was added at
a dose of 40 mg b.i.d., the patient’s depression rating score A population-based cohort study of older adults on tra-
declined sharply from a pretreatment Hamilton Depression ditional MAOIs utilizing large administrative healthcare
Rating Scale score of 22 to only 9 after 4 months. The case databases in Ontario, Canada [45] examined prescription
report requires further replication, but is yet another patterns and safety issues. In a ten-year period, only 348
example of the potential role of MAOIs in severely ill new continuous users of traditional MAOIs were identi-
refractory depressed patients. fied in a population of 1.4 million older adults in
MAOIs continue to be listed as second or third line Ontario. Yearly incidence rates of MAOI prescriptions
options for treatment resistant depression, atypical decreased from 3.1/100,000 in 1997 to 1.4/100,000 in
depression or bipolar depression in most of the major 2006. This occurred during a period of time when anti-
consensus guidelines including the American Psychiatric depressants overall were being prescribed at an increas-
Association [35] and the Canadian Network for Mood and ing rate (10,900/100,000 population) in older adults
Anxiety Treatments (CANMAT) [36]. The American compared to MAOIs where the prescription rate was only
Psychiatric Association, CANMAT, the Texas Algorithm 21.3/100,000 older adults. Not surprisingly, the MAOIs
Project [37], and the British Association for Psychophar- were being used for older adults who had a high prior
macology [38] also recommend MAOIs for treatment of rate of use of other antidepressants as well as ECT thus
bipolar depression. Despite the significant safety concerns confirming its role in refractory depression. In this study,
including tyramine and drug interactions, and the lack of safety concerns were addressed and despite a significant
industry promotion, irreversible MAOIs continue to be a rate of concomitant exposure to at least one serotonin
treatment recommendation by expert clinicians for treat- drug (18.1 %) with MAOIs, no case of hypertensive
ment resistant depression, atypical depression and bipolar crisis or serotonin syndrome was identified in this
depression. A Dutch algorithm for pharmacological database.
MAOIs in the Treatment of Depression 793

7 Second Generation MAOIs antidepressants. For example, in a meta-analysis by Lot-

ufo-Neto et al. [51], 66 studies of moclobemide published
7.1 History between 1984 and 1996 were included. The response rate
of moclobemide was 58 % and no different compared to
In an attempt to capitalize on the perceived efficacy of other antidepressants including TCAs and SRIs. The
traditional irreversible MAOIs for atypical and treatment response rate of moclobemide in studies with placebo was
refractory depression, drug development began to focus on 49 %, and favoured moclobemide significantly by 15.8 %,
selective and reversible MAOIs, in order to improve safety though the authors noted that the drug-placebo difference
and convenience. Because hypertensive crises are caused was somewhat smaller compared to similar studies with
by the inhibition of MAO-A in the gut, selective inhibitors irreversible MAOIs. When they compared moclobemide to
of MAO-B were developed. Selegiline is a selective MAO- individual antidepressants, they found no significant dif-
B inhibitor at low doses, but it was eventually determined ferences with response rates compared to SRIs and TCAs,
that it was only at higher doses, when selegiline inhibits but lower rates compared to four studies with irreversible
both MAO-A and MAO-B, that it possessed antidepressant MAOIs. In terms of safety, the most common adverse
benefits. The next drugs developed were the selective event was insomnia followed by GI disturbances, and only
reversible inhibitors of MAO-A. Because these drugs do one hypertensive crisis was documented. The authors
not bind irreversibly to the MAO in the gut, tyramine is concluded that moclobemide was as effective as SRIs, and
able to displace these drugs, dramatically decreasing its safer and better tolerated than irreversible MAOIs and
ability to raise blood pressure. The reversible MAO-A TCAs, with the clear advantage of having fewer sexual
inhibitors brofaromine and moclobemide were developed, adverse events compared to other antidepressants. Inter-
but only the latter was eventually marketed [46]. estingly, the authors also noted the ‘‘clinical impression’’ of
More recently development took another approach to MDs in Mexico, Canada, Brazil, the UK, and Europe that
avoid the potential for hypertensive crises. Transdermal moclobemide was not as effective as the irreversible
drug delivery systems avoid first pass metabolism and MAOIs. Other meta-analyses found similar results includ-
result in inhibition of MAO in the brain while minimizing ing analyses that focused on studies comparing moclobe-
MAO inhibition in the gut. Transdermal selegiline was mide, a relatively activating antidepressant, to more
approved by the FDA in 2006, and at low doses (6 mg/ sedating antidepressants for the treatment of agitated,
24 h) can be administered without dietary restrictions [47]. anxious depression [52]. A meta-analysis of MAOIs com-
In spite of improved safety and fewer dietary restric- pared to other antidepressants for the treatment of atypical
tions, the use of moclobemide and transdermal selegiline depression found only two studies with moclobemide [30].
never reached the popularity of drugs like the SRIs or A small study (N = 53) of moclobemide compared to
SNRIs. While this may be due to concerns about poor fluoxetine found a slight advantage for moclobemide [53],
efficacy (see below) it is also likely due to their place in while a larger study comparing moclobemide to sertraline
clinical practice guidelines. For example, in the American (N = 172) found better efficacy for sertraline [54]. These
Psychiatric Association Practice Guidelines for major authors concluded that more studies of patients with
depression [35], MAOIs are not recommended as first line atypical depression using moclobemide are necessary.
agents but traditional MAOIs or the transdermal selegiline Finally, while more studies are clearly required, there is
can be considered options for patients who have not some evidence that moclobemide might be effective for
responded to SRIs (moclobemide is not available in the dysthymia [55], and may not be as effective as TCAs for
US). Other guidelines also omit MAOIs as first line agents elderly depressives [56].
and designate them as being for use by specialists only, and
frequently never distinguish between traditional MAOIs 7.3 Efficacy and Safety of Transdermal Selegiline
and moclobemide or transdermal selegiline [48–50]. One
of the few guidelines to include moclobemide as a first line Unlike the large number of studies examining the efficacy
antidepressant is CANMAT [36]. In these guidelines, and safety of moclobemide, there are only four published
selegiline transdermal is mentioned as a second line agent randomized controlled trials of transdermal selegiline. The
even though it has not been approved by Canadian Health first published study included 177 out-patients with a fixed
Regulatory agencies nor is it marketed in Canada. dose of selegiline compared to placebo in which selegiline
resulted in statistically significant benefits after six weeks
7.2 Efficacy and Safety of Moclobemide on all outcome measures [57]. In a larger second study with
365 outpatients, 8 weeks of fixed-dose transdermal seleg-
Numerous meta-analyses have documented the efficacy iline was modestly but statistically significantly better than
and safety of moclobemide compared to placebo and other placebo on the primary outcome measures of depression
794 K. I. Shulman et al.

[58]. In a third flexible-dose study of 265 patients, trans- treatment should be at least 6 weeks in duration at a
dermal selegiline was again modestly but significantly maximum tolerated dose. Furthermore, in addressing the
better than placebo [59]. The fourth study was a 52-week, safety concerns about MAOIs, he notes that in over
double-blind, fixed-dose study of relapse prevention in 312 40 years of practice he has observed only one case of
patients [60]. Significantly fewer selegiline patients hypertension with headache that was induced by a die-
(16.8 %) relapsed after 52 weeks compared to placebo tary factor but was easily managed on an outpatient
(30.7 %). Selegiline treated patients in these studies basis. In reviewing his personal University practice over
experienced more insomnia and more application site skin a five-year period, with a selection bias towards refrac-
reactions but virtually no weight gain or sexual adverse tory depressive patients, he identified seven patients who
events. Also notable was the fact that there were no were given a trial of MAOIs. Six of those patients
hypertensive crises in 2,553 patients treated with trans- achieved remission. He makes a strong case for main-
dermal selegiline in spite of the lack of dietary restrictions taining this class of drugs in the therapeutic armamen-
in most of the drug development trials [47]. Finally, from a tarium for refractory depressions and thereby not
clinical standpoint, it is notable that these trials demon- depriving the patients of a potentially useful and even
strated very high rates of treatment adherence (84–90%) life saving treatment.
suggesting excellent patient acceptance [14].
Despite reasonable evidence for the effectiveness of
selective and reversible MAOIs in the treatment of major 9 Conclusion
depression they have not replaced irreversible MAOIs in
the therapeutic armamentarium for atypical depression or The number of patients with atypical, treatment resistant
treatment refractory depression. or bipolar depression who may potentially benefit from
MAOIs is substantial [22] and therefore MAOIs could
play a role in a much larger proportion of patients than is
8 Why Are Irreversible MAOIs Not Used More Often? currently observed. Moreover, the recent reassuring evi-
dence regarding safety concerns should encourage clini-
Traditional MAOIs are not being used despite continued cians to be bolder with the use of this class of drugs
recommendations by opinion leaders, and the inclusion of including the use of practical and safe dietary recom-
MAOIs in a wide range of consensus guidelines and mendations while still being alert to the potential for drug
treatment algorithms, especially for atypical depressions interactions, especially with serotonergic agents and
and treatment refractory depressions. The recent study by amphetamine-like drugs.
Shulman et al. [45] demonstrates that current use of There has been a recent flurry of ‘clarion calls’ to rally
MAOIs appears to be safe and has not resulted in the interest in the use of MAOIs reflected by terms such as
feared hypertensive crises or serotonin syndromes. ‘unrequited class of anti-depressants’ [62], ‘risks, benefits
Because there are no major pharmaceutical companies and lore’ [14] and ‘relics reconsidered’ [63]. Indeed,
promoting MAOIs and due to their ‘‘bad reputation’’, a Goldberg and Thase [64] have argued that MAOIs repre-
whole generation of psychiatrists has virtually no expe- sent a currently available ‘secret weapon’ that provides
rience or knowledge of MAOI use, thereby depriving a triple reuptake inhibition. It is really up to experienced
subgroup of seriously ill depressive patients from a clinicians, the profession and the academic community to
potentially useful treatment. maintain within our therapeutic armamentarium, treatments
In a recent personal opinion paper, Fawcett [61] a that are not promoted by industry yet require special
respected psychopharmacology expert speculates about training and knowledge that should be incorporated into
why this has occurred. He notes that because of limited psychiatry education programs. In this way we can main-
numbers available for clinical trials, guidance for this tain a treatment that has the potential to benefit a vulner-
class of drugs is really dependant on the personal able and substantial sub-population of mood disorder
experience of opinion leaders. He emphasizes that in his patients.
clinical experience, a number of patients with treatment
Acknowledgments Dr. Shulman is supported in part by the Lewar
resistant depression do achieve remission when given a Chair in Geriatric Psychiatry. Dr. Shulman, Dr. Herrmann and Dr.
trial of MAOIs. He emphasizes that a full course of Walker have no conflicts of interest to declare.
MAOIs in the Treatment of Depression 795

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