Adult ADHD vs.

Bipolar Disorder in the DSM-5 Era:

MICHAEL J. BRUS, MD
A Challenging Differentiation for Clinicians MARY V. SOLANTO, PhD
JOSEPH F. GOLDBERG, MD

Objective. Patients with adult attention-deficit/ ential diagnosis, Diagnostic and Statistical Manual of
hyperactivity disorder (ADHD) and bipolar disor- Mental Disorders, DSM-5, medication response,
der can present with similar symptoms, including comorbidity
increased energy, distractibility, disorganization,
impulsivity, hyperactivity, and rapid speech.
Determining whether the patient has either, or When presented with an adult patient with
possibly both, of these syndromes can be a com- increased energy, distractibility, disorganization,
plex task. This review attempts to clarify where impulsivity, hyperactivity, and rapid speech, the cli-
these disorders overlap, both symptomatically nician may formulate a differential diagnosis that
and epidemiologically, and where they diverge, to includes both bipolar disorder and attention-
help clinicians increase the accuracy of their deficit/hyperactivity disorder (ADHD). However,
diagnoses. Changes to diagnostic criteria from the determining whether the patient has either, or possi-
fourth to the fifth edition of the Diagnostic and bly both, of these syndromes can be a complex task.
Statistical Manual of Mental Disorders (from In this article, we clarify where these disorders over-
DSM-IV-TR to DSM-5) are discussed, as is the evi- lap, both symptomatically and epidemiologically, and
dence base for pharmacological treatments. where they diverge to help clinicians better differen-
Method. Studies and sources were identified using tiate these syndromes.
computerized searches. Results. Adult ADHD and According to the National Comorbidity Survey
bipolar disorder have multiple overlapping symp- Replication (NCS-R), a nationally representative
toms, but there are differences in prevalence diagnostic assessment of thousands of Americans,
(ADHD affects 4.4% of adults in the United States ADHD affects 4.4% of adults,1 while bipolar disorder
versus 1.4% for bipolar disorder), onset of symp- affects 1.4% (0.6% with bipolar I and 0.8% with bipo-
toms (usually before age 7 years in ADHD versus lar II).2 Sixty-two percent of those with ADHD are
after age 12 years in bipolar disorder), disease male,1 while there are no gender differences among
course (chronic in ADHD versus cyclical in bipo- adults with bipolar disorder.2 Although studies con-
lar disorder), mood symptoms (absent in ADHD cerning rates of misdiagnosis of these two disorders
but always present in bipolar disorder), and psy- in adults are lacking, misdiagnosis is something that
chotic symptoms (absent in ADHD but sometimes many clinicians have repeatedly observed. One fac-
present in bipolar disorder). Approximately 20% tor that may lead to misdiagnosis is that adults with
of adult patients with ADHD also have bipolar dis- ADHD are more likely to present with comorbid
order, while 10%–20% of patients with bipolar dis-
order have adult ADHD. Comorbidity of bipolar BRUS: Icahn School of Medicine at Mt. Sinai, New York, NY;
disorder and ADHD is associated with an earlier SOLANTO: New York University School of Medicine, New York,
age of onset and a more chronic and disabling NY; GOLDBERG: Icahn School of Medicine at Mt. Sinai and
course of bipolar disorder, as well as more psychi- Silver Hill Hospital, New Canaan, CT.
atric comorbidity. Conclusion. Distinguishing Copyright ©2014 Lippincott Williams & Wilkins Inc.
between adult ADHD and bipolar disorder Please send correspondence to: Michael J. Brus, MD, Icahn
requires careful attention to phenomenology and School of Medicine at Mt. Sinai, 16 East 96th St., Suite 1A, New
York, NY 10128. [email protected]
awareness of epidemiology, with a focus on child-
hood history, lifetime course of symptoms, and the Joseph Goldberg: Scientific Advisory Board: Avanir Pharmaceu-
ticals, Mylan Pharmaceuticals. Consultant: Medical Communi-
possibility of comorbidity. (Journal of Psychiatric cations, MedScape, WebMD. Speakers’ Bureau: Astra Zeneca,
Practice 2014;20:428–437) Merck, Mylan Pharmaceuticals, Novartis, Sunovion, Takeda.
Royalties: American Psychiatric Publishing, Inc. The other
KEY WORDS: attention-deficit/hyperactivity disorder authors declare no conflicts of interest.
(ADHD), bipolar disorder, bipolar I, bipolar II, differ- DOI: 10.1097/01.pra.0000456591.20622.9e

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

major depressive disorder (MDD) and dysthymia Several of the diagnostic criteria for ADHD and
than those without ADHD. For example, the NCS-R bipolar disorder are similar. For example, one of the
reported that 18.6% of patients with adult ADHD ADHD symptoms from the inattentive cluster, “is
have MDD, and 12.8% have dysthymia, compared to often easily distracted by extraneous stimuli,” direct-
7.8% and 1.9%, respectively, among people without ly overlaps with the bipolar disorder criterion of “dis-
adult ADHD.1 This ADHD-MDD comorbidity could tractibility (i.e., attention too easily drawn to
lead a clinician to mistake ADHD symptoms for unimportant or irrelevant external stimuli), as
manic symptoms in a patient who had previously reported or observed.” At least two ADHD symptoms
had a major depressive episode. from the hyperactive/impulsive cluster appear to
overlap with bipolar disorder criteria. The ADHD cri-
Overlapping Diagnostic Criteria terion “is often ‘on the go,’ acting as if ‘driven by a
motor’” may appear to overlap with the bipolar dis-
The first step in correctly diagnosing ADHD and order criterion “increase in goal-directed activity
bipolar disorder is to become thoroughly familiar (either socially, at work or school, or sexually) or psy-
with their phenomenology. Adult ADHD is a chronic chomotor agitation (i.e., purposeless non-goal direct-
disorder with childhood onset. As seen in Table 1, the ed activity).” Likewise, the ADHD criterion “often
symptoms as described in the criteria in the fifth edi- talks excessively” overlaps with the bipolar disorder
tion of the Diagnostic and Statistical Manual of criterion “more talkative than usual or pressure to
Mental Disorders (DSM-5) fall into two clusters, inat- keep talking.” Two other ADHD criteria—”often
tention and hyperactivity/impulsivity.3 There are blurts out an answer before a question has been com-
nine inattention symptoms and nine hyperactivity/ pleted” and “often interrupts or intrudes on others”—
impulsivity symptoms. In adults, DSM-5 requires could also be construed as overlapping with the
five symptoms in a given cluster over the previous 6 “talkativeness” criterion for bipolar disorder.
months for a diagnosis in that subtype (called a “pre-
sentation specifier” in DSM-5). In a study of 107 Differentiating Criteria
adults with ADHD published by Wilens et al. in
2009, 62% had the combined subtype, 31% had the Despite these areas of overlap, some pragmatic
predominantly inattentive subtype, and 7% had the strategies can help distinguish ADHD from bipolar
predominantly hyperactive subtype.4 These results disorder. Age of onset is perhaps the most salient fea-
are similar to the subtype prevalences found in chil- ture. DSM-5 requires that “several” ADHD symp-
dren in the DSM-IV field trials.5 Wilens et al. found toms appear before age 12 years. This age cutoff is
no gender differences by subtype, but they reported higher than the age 7 cutoff used in the DSM-IV-TR,7
that the combined subtype was associated with more but it is still younger than the age at which the vast
psychiatric comorbidities.4 majority of first manic episodes manifest.6 As noted
Bipolar disorder is an episodic disorder with onset in DSM-5, “bipolar disorder is rare in preadoles-
any time from childhood to middle adulthood.6 Its cents.” Onset of bipolar disorder before age 13 years
cardinal feature is a lifetime history of at least one has been reported to occur in just 2%–16% of cohorts
manic or hypomanic episode. As seen in Table 1, to in Europe.6 Even in the United States, where
qualify for a manic or hypomanic episode, patients 22%–28% of bipolar cases have been reported to
must meet Criterion A, which requires a “distinct occur before age 13,6 age of onset falls far earlier in
period of abnormally and persistently elevated, ADHD, as nearly all children reach the symptomatic
expansive, or irritable mood” and “persistently threshold by age 12 and the vast majority show
increased goal-directed activity or energy” lasting for impairment by age 7. Specifically, 95% of those meet-
at least 1 week or requiring hospitalization (manic ing symptomatic criteria for ADHD in the NCS-R
episode) or lasting at least 4 days (hypomanic recalled age of onset by age 12 (and 99% by age 17).1
episode).3 There are seven “B Criteria” for a manic or Moreover, DSM-IV field trial data concerning youth
hypomanic episode, at least three of which are with ADHD indicated that 82% showed impairment,
required if the patient’s mood is elevated or expan- and 96% showed at least one symptom, before age 7
sive, and four of which are required if the patient’s years, the age cut-off in DSM-IV.8 (Among subjects
mood is irritable. with the hyperactive-impulsive subtype, 98% showed

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

Table 1. Overlapping DSM-5 diagnostic criteria for ADHD and manic/hypomanic episodes
Attention Deficit/Hyperactivity Disorder Manic or Hypomanic Episode
A. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with A. A distinct period of abnormally and
functioning or development, as characterized by (1) and/or (2): persistently elevated, expansive, or
1. Inattention: Six (or more) of the following symptoms have persisted for at least 6 irritable mood and abnormally and
months to a degree that is inconsistent with developmental level and that negatively persistently increased goal-
impacts directly on social and academic/occupational activities: directed activity or energy,
Note: The symptoms are not solely a manifestation of oppositional behavior, defiance, lasting at least 1 week (for a manic
hostility, or failure to understand tasks or instructions. For older adolescents and episode, or 4 consecutive days for
adults (age 17 and older), at least five symptoms are required. hypomanic episode) and present
most of the day, nearly every day (or,
a. Often fails to give close attention to details or makes careless mistakes in
in a manic epidose, for any duration
schoolwork, at work, or during other activities (e.g., overlooks or misses details, work
if hospitalization is necessary).
is inaccurate).
b. Often has difficulty sustaining attention in tasks or play activities (e.g., has B. During the period of mood
difficulty remaining focused during lectures, conversations, or lengthy reading). disturbance and increased energy or
c. Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, activity, three (or more) of the
even in the absence of any obvious distraction). following symptoms (four if the mood
d. Often does not follow through on instructions and fails to finish schoolwork, chores, is only irritable) are present to a
or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily significant degree and represent a
sidetracked). noticeable change from usual
e. Often has difficulty organizing tasks and activities (e.g., difficulty managing behavior:
sequential tasks; difficulty keeping materials and belongings in order; messy, 1. Inflated self-esteem or
disorganized work; has poor time management; fails to meet deadlines). grandiosity.
f. Often avoids, dislikes, or is reluctant to engage in tasks that require sustained 2. Decreased need for sleep (e.g.,
mental effort (e.g., schoolwork or homework; for older adolescents and adults, feels rested after only 3 hours of
preparing reports, completing forms, reviewing lengthy papers). sleep).
g. Often loses things necessary for tasks or activities (e.g., school materials, pencils, 3. More talkative than usual or
books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones). pressure to keep talking.
h. Is often easily distracted by extraneous stimuli (for older adolescents and
4. Flight of ideas or subjective
adults, may include unrelated thoughts).
experience that thoughts are
i. Is often forgetful in daily activities (e.g., doing chores, running errands; for older
racing.
adolescents and adults, returning calls, paying bills, keeping appointments).
2 Hyperactivity and impulsivity: Six (or more) of the following symptoms have persisted 5. Distractibility (i.e., attention
for at least 6 months to a degree that is inconsistent with developmental level and that too easily drawn to
negatively impacts directly on social and academic/occupational activities: unimportant or irrelevant
Note: The symptoms are not solely a manifestation of oppositional behavior, defiance, external stimuli), as reported
hostility, or a failure to understand tasks or instructions. For older adolescents and or observed.
adults (age 17 and older), at least five symptoms are required. 6. Increase in goal-directed
a. Often fidgets with or taps hands or feet or squirms in seat. activity (either socially, at
b. Often leaves seat in situations when remaining seated is expected (e.g., leaves his or work or school, or sexually) or
her place in the classroom, in the office or other workplace, or in other situations psychomotor agitation (i.e.,
that require remaining in place). purposeless non-goal-directed
c. Often runs about or climbs in situations where it is inappropriate. (Note: In activity).
adolescents or adults, may be limited to feeling restless.) 7. Excessive involvement in
d. Often unable to play or engage in leisure activities quietly. activities that have a high
e. Is often “on the go,” acting as if “driven by a motor” (e.g., is unable to be or potential for painful consequences
uncomfortable being still for extended time, as in restaurants, meetings; (e.g., engaging in unrestrained
may be experienced by others as being restless or difficult to keep up buying sprees, sexual
with). indiscretions, or foolish business
f. Often talks excessively. investments).
g. Often blurts out an answer before a question has been completed (e.g.,
completes people’s sentences; cannot wait for turn in conversation).
h. Often has difficulty waiting his or her turn (e.g., while waiting in line). Overlapping symptoms are shown in
i. Often interrupts or intrudes on others (e.g., butts into conversations, bold.
games, or activities; may start using other people’s things without asking Reprinted with permission from the
or receiving permission; for adolescents and adults, may intrude into or DSM-5 (copyright 2013). American
take over what others are doing). Psychiatric Association.3

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

impairment, and 100% showed at least one symp- tation. All of these features may superficially resem-
tom, before age 7 years. Among those with the inat- ble the presentation of an adult patient with ADHD
tentive subtype, those figures were 57% and 85%, with both inattentive and hyperactive/ impulsive fea-
respectively.8) tures. For example, “psychomotor agitation (i.e., pur-
Another key distinction between adult ADHD and poseless non-goal directed activity)” closely resembles
bipolar disorder is the persistent rather than episodic the ADHD symptoms of “fidget[ing] with or tapp[ing]
display of symptoms in patients with ADHD. Patients hands or feet or squirm[ing] in seat,” “feeling restless,”
with adult ADHD can display symptoms throughout “leav[ing] seat in situations when remaining seated is
life at any time as a baseline characteristic, while expected,” and being “‘on the go,’ acting as if ‘driven by
patients with bipolar disorder, by definition, suffer a motor.’” However, even in this example, it is possible
discrete periods of illness that represent departures to distinguish the two disorders. For example, while
from a baseline or “usual” state. On the other hand, “irritable mood” may be less specific to mania than an
ADHD symptoms and functional impairment do “elevated” or “expansive” mood, it is not a mood often
attenuate over the life cycle, at least in the sense that found in patients with ADHD.
ADHD is a childhood disorder that persists into adult- The existence of symptom overlap between ADHD
hood in only about half of cases.9 De novo onset of and bipolar disorder has led some to hypothesize that
adult ADHD in the absence of childhood symptoms the disorders are overdiagnosed because the same
has not been demonstrated. By contrast, the long- symptoms are being counted twice. One study has
term course of bipolar disorder seldom involves an addressed this issue. Milberger et al. re-assessed 20
attenuation of symptoms or attenuation of functional adult patients with the comorbid conditions, account-
impairment. Most individuals (especially those with ing for overlapping DSM-III-R symptoms.11 Depen-
early onset in late adolescence or young adulthood) ding on how the overlapping symptoms were
have multiple episodes and, according to at least some accounted for, between 15 and 16 of the 20 patients
natural history studies, the duration of intervals (75%–80%) retained their ADHD diagnosis, and
between episodes may become shorter over the course between 12 and 18 of the 20 patients (60%–90%)
of time.10 retained their bipolar disorder diagnosis. The same
In DSM-5 itself, it is acknowledged that “many study re-assessed 15 children and adolescents,
[ADHD] symptoms overlap with the symptoms of accounting for overlapping symptoms in the same
mania.” However, the classic manic patient with bipo- fashion. All 15 of the children kept their ADHD diag-
lar I disorder—the “elevated” or “expansive” type—is nosis (100%), and between 7 and 12 of the 15
not easy to confuse with a patient with ADHD, (50%–75%) kept their bipolar disorder diagnosis.
whether adult or child. The manic patient may display Although it is not a formal diagnostic criterion for
grandiose or erotomanic delusions; show extremely either of the disorders, emotional lability may draw
rapid speech characterized by loose associations and the attention of clinicians during an evaluation, as
wordplay; take sexual, financial, or physical risks; and cyclothymic temperaments have been described in
stay up for days on end pursuing quixotic projects both bipolar disorder and adult or childhood
with a frantic energy. This contrasts with even ADHD.12,13 In bipolar disorder, patterns of mood labil-
extreme forms of ADHD, which are never character- ity have been shown to vary from euthymia to depres-
ized by delusions or formal thought disorder, and sion or elation, or from depression to elation, rather
which feature risk-taking of a less severe variety. than from euthymia to anger (as observed more often
However, these distinctions blur somewhat when in patients with borderline personality disorder).14 By
the differential is between ADHD and certain presen- contrast, mood lability in ADHD has been described
tations of bipolar II disorder. For example, a patient more as deficient emotional self-regulation that can
could present with a hypomania that lacks many of involve temper outbursts and low frustration toler-
the “classic” features of manic states, such as eupho- ance in response to stress.15
ria, grandiosity, a decreased need for sleep, and an Critical to the phenomenologic distinction between
increase in productive behavior. Such a patient could bipolar disorder and ADHD is recognizing their
qualify for a hypomanic episode with irritable mood unique, non-overlapping symptoms, as summarized
and a combination of talkativeness, racing thoughts, in Figure 1. Features such as psychosis and suicidal-
distractibility, and non-goal directed psychomotor agi- ity are common in individuals with bipolar disorder

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

Figure 1. Symptoms of bipolar disorder and attention-deficit/hyperactivity disorder

Bipolar disorder ADHD

Definable, discrete episodes Inattention Non-discrete, chronic symptoms

Rare onset in childhood Executive dysfunction Always onset in childhood
Prominent depression Impulsivity Depression not prominent
Psychosis during mania (BP I) Sensation-seeking No psychosis
Suicidality Restlessness No suicidality
Grandiosity Substance use comorbidity No grandiose beliefs
Hypersexuality No hypersexuality
Reduced need for sleep If less sleep, consequent fatigue

but quite rare in those with ADHD. Among potential the context of a new-onset euphoric, elevated, or irri-
overlapping symptoms, Geller et al. identified five table mood. Moreover, high energy states in mania or
key features—elation, grandiosity, decreased need hypomania usually are linked to purposeful, goal-
for sleep, racing thoughts, and hypersexuality—as directed activities (such as the pursuit of financial or
“cardinal” in mania/hypomania and seldom evident other high-reward activities), whereas the hyperac-
in ADHD.16 tivity associated with ADHD is often not necessarily
directed toward a specific goal or achievement.
Changes in DSM-5 A second significant change in DSM-5 was the
committee’s decision to loosen the age-of-symptom-
While the main symptom clusters in ADHD and onset requirement for ADHD. DSM-IV-TR required
bipolar disorder, and their associated textual that “some hyperactive-impulsive or inattentive
descriptions, remain largely the same as in DSM-IV, symptoms that caused impairment were present
three important changes were made in DSM-5. before age 7 years,” while DSM-5 requires that “sev-
First, DSM-5 has added to the stem criterion for eral inattentive or hyperactive-impulsive symptoms
manic and hypomanic episodes (Criterion A in Table were present prior to age 12.” Although the DSM-5
1). For a patient to qualify for mania or hypomania committee made this change in part to accommodate
in DSM-IV-TR, the person simply needed to display a patients who are not diagnosed until adulthood and
“persistently elevated, expansive, or irritable mood,” may have problems with retrospective recall of child-
in addition to three or four of the seven Criterion B hood symptom onset, and although the committee
symptoms (Criterion B in Table 1) However, the believed that this change would have a “negligible”
DSM-5 committee elevated one of these “B” (non- impact on the rate of ADHD diagnoses,18 this change
mandatory) symptoms (“increase in goal-directed in the age-of-symptom-onset criterion may make it
activity … or psychomotor agitation”) to an “A” (nec- more difficult to distinguish ADHD from hypomanic
essary) criterion (“persistently increased goal-direct- symptoms when they first appear at age 11 or 12—
ed activity or energy”) based on studies showing that the end of the ADHD symptom window and the
psychomotor activation robustly discriminated bipo- beginning of the bipolar disorder window.
lar from unipolar depression.17 However, when examining an adult patient who
To minimize diagnostic confusion in the wake of remembers onset of symptoms at age 10 or 11 years,
this change, when clinicians evaluate energy and the astute clinician would be advised to remember
activity levels they must differentiate hyperactivity the DSM-IV field trial data indicating that symptom
as an ADHD-associated trait from the psychomotor onset in ADHD is usually before age 7, when very
acceleration that arises as a change from baseline in few cases of mania appear. The clinician may then

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

wish to further investigate corroborative sources of ADHD is usually observed rapidly, within hours to
information, to see if symptom onset can be pinned days), the targeted effects of agents on attentional
down to an earlier age when a bipolar disorder diag- versus behavioral (e.g., impulsivity-hyperactivity)
nosis would be extremely unlikely. domains in ADHD, and the potential for adverse cog-
A third significant change in the criteria for ADHD nitive effects with mood stabilizers and antipsy-
in DSM-5 is the lowering of the symptom threshold chotics. Notably, many of the clinical trials described
for making the diagnosis in adults. Specifically, only in Table 2 focused on childhood or adolescent ADHD,
five, rather than six symptoms in either the inatten- which limits extrapolation to adult ADHD. Of course,
tive or hyperactive-impulsive domain are required. the treatment implications for ADHD and bipolar
This change was based on studies indicating that disorder extend beyond pharmacology, as the psy-
adults who score 1.5 standard deviations or more chotherapeutic and psychosocial management of
above the normative mean typically endorse fewer these disorders differs as well.
than 6 symptoms.19,20 This may be expected to have
the effect of increasing the likelihood that ADHD will Comorbidity of Bipolar Disorder and ADHD
be diagnosed in adults.
It should be noted that relying on symptoms and In addition to distinguishing between bipolar disor-
phenomenology to distinguish these disorders has its der and adult ADHD, it is also important to recognize
limits, even when done by an expert clinician. For that the disorders may occur together. Although, as
that reason, the National Institute of Mental Health mentioned earlier, data for rates of misdiagnosis are
(NIMH) has proposed an alternative and controver- lacking, rates of comorbidity of bipolar disorder and
sial nosology in which dimensions of psychopathology adult ADHD have been catalogued more rigorously.
are considered only if they have been shown to map The NCS-R found comorbid ADHD in 21% of
to a known gene or neural circuit.21 However, until adults with bipolar disorder.1 Another extensive
valid biomarkers are established for any psychiatric study of ADHD comorbidity in populations with bipo-
diagnosis, a careful descriptive phenomenological lar disorder was Nierenberg et al.’s evaluation of the
approach remains the standard of care for clinicians. first 1,000 participants in the Systematic Treatment
Enhancement Program for Bipolar Disorder (STEP-
Prognosis and Response to Treatment BD), a multicenter trial of treatments for patients
with bipolar disorder sponsored by the National
Differentiating ADHD and bipolar disorder has Institute of Mental Health.40 This study found a life-
important implications for prognosis and treatment. time prevalence of ADHD of 9.5% (14.7% among
For example, a patient with bipolar disorder is at males, 5.8% among females) in the first 1,000
constant risk for manic or depressive episodes poten- patients with bipolar disorder who enrolled in STEP-
tially leading to acutely self-destructive or self-inju- BD. However, the prevalence of comorbid ADHD
rious behavior and the clinician must weigh the depended strongly on the age of onset of the bipolar
benefits and risks of prescribing mood-stabilizing disorder. Among patients with onset of bipolar disor-
medications. These medications offer the benefit of der before age 18 years, 13% met ADHD criteria;
symptomatic and functional control in patients with among those with disease onset at age 18 or older,
bipolar disorder, but they usually take weeks to only 5% met criteria for ADHD. Over the last 5 years,
months to show efficacy and are often associated multiple studies of adult populations with bipolar
with risks of side effects such as weight gain, seda- disorder have found adult ADHD comorbidity rates
tion, and cognitive dulling.22 Thus, the “cost” of pre- approximately between the 9.5% found in STEP-BD
scribing such medications to patients with ADHD and the 21% found in NCS-R.41–46 The one study that
who have been misdiagnosed as having bipolar dis- found a much higher rate of adult ADHD comorbidi-
order is significant. ty (30%) was the only one that assessed ADHD using
The potential effects of various drug classes in only a self-report instrument without a follow-up
patients with bipolar disorder and in those with clinical interview.47 Those studies that also deter-
ADHD are summarized in Table 2. Key points of mined the comorbidity of childhood ADHD that
comparison involve the expected time course of drug remitted in adulthood reported a total comorbidity
effects (e.g., the efficacy of stimulant medication for rate (combined current and childhood-only ADHD) in

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

Table 2. Anticipated effects of psychotropic medications in bipolar disorder versus ADHD

Agent Likely responses in bipolar disorder Likely responses in ADHD

Psychostimulants Could exacerbate manic or psychotic symptoms. Organizing, calming effect,

May help depressive symptoms23 but must monitor improves both attentional and
for risk of mood destabilization. motor symptoms, relatively
Stimulant use may be associated with younger age at rapid onset.
24
onset in youth with bipolar disorder.
In youth with comorbid ADHD and bipolar disorder,
adjunctive mixed amphetamine salts added to
25
divalproex may improve ADHD symptoms, while
adjunctive methylphenidate may be ineffective for
ADHD symptoms when co-administered with
26
aripiprazole.
Alpha2 agonists Case reports of secondary mania in children treated May be especially helpful for
(e.g., guanfacine, for ADHD; no published reports in patients with impulsivity, hyperactivity, and
clonidine) known bipolar disorder. frustration tolerance, although
27
modest effect sizes.
Noradrenergic Despite theoretically greater risk for induction of Desipramine > placebo in
agents (e.g., mania/hypomania with noradrenergic drugs in children/adolescents with
atomoxetine, patients with bipolar disorder, open-label ADHD, equally effective for
nortriptyline, atomoxetine added to antimanic drugs significantly attentional and behavioral
29
desipramine) improved ADHD symptoms without worsening domains.
28
mania symptoms in comorbid youth.
Other Controversial efficacy, and risk for mood Bupropion ~2.5-fold greater
30
antidepressants destabilization. efficacy than placebo.31 other
antidepressants less well-
established.
Dopamine agonists Efficacy in bipolar depression without inducing Theoretically could improve
32,33
(e.g., mania. Pramipexole may improve cognitive attentional processing, but no
bromocriptine, function in patients with bipolar disorder who are published open or randomized
34
pramipexole, euthymic. trials.
ropinirole)
Lithium Robust antimanic efficacy. Comparable efficacy to
May cause modest impairment in associative fluency, methylphenidate for reducing
verbal memory, short- and long-term memory, irritability and aggression in
35 36
motor speed. adult ADHD.
Divalproex Robust antimanic efficacy. Stimulant plus divalproex more
May cause subtle attentional and verbal memory effective for ADHD-associated
35
deficits. aggression than stimulant plus
37
placebo.
Carbamazepine Robust antimanic efficacy. Inferior to clonidine for treating
May cause subtle learning deficits and delayed impulsivity and hyperactvity
35 38
visuospatial processing. in children with ADHD.
Lamotrigine Prophylactic > acute efficacy. No data in ADHD.
More robust against recurrent depression than
mania.
No documented adverse cognitive effects in bipolar
disorder.
Atypical In youth with comorbid disorders, aripiprazole Possible efficacy for impulsivity-
39
antipsychotics improved mania but not ADHD symptoms. aggression but no known
benefit for attentional
processing in ADHD.

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 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

adults with bipolar disorder ranging from just under to a rate of about 20% for bipolar disorder comorbidi-
30%41–43 to 37.8%.46 ty in cohorts with adult ADHD. The researchers in
The data from STEP-BD highlighting the impor- these studies did not comment on whether bipolar
tance of bipolar age of onset were consistent with disorder comorbidity was associated with severity of
those of many other studies of adult populations illness, age of onset, functional impairment, or other
with bipolar disorder.41,43,44,46,48 For instance, Sachs psychiatric comorbidity. It should be noted that all of
et al.48 found that patients with bipolar disorder with these comorbidity studies involving cohorts with
a history of childhood ADHD had a mean age of onset bipolar disorder or ADHD based their ADHD diag-
of bipolar disorder at age 12.1 years, while patients noses on retrospective recall of childhood symptoms
with bipolar disorder without a history of childhood rather than on prospective observation of child
ADHD had a mean age of onset of bipolar disorder at probands. Thus, it is possible that current symptoms
age 20 years. Tamam et al.41 found that a majority of bias recall of childhood symptoms so that more
those with either current or past ADHD comorbidity ADHD-like symptoms are “recalled.”
had onset of bipolar disorder before age 18 years,
while 85% of those with bipolar disorder alone had Conclusion
onset at age 18 years or older.
Not only is comorbidity of bipolar disorder and Distinguishing between adult ADHD and bipolar
ADHD associated with earlier age of bipolar disorder disorder presents many challenges for clinicians.
onset, but a wealth of evidence indicates that Although the existence of phenomenological overlap,
patients with comorbid ADHD suffer a more chronic the high prevalence of depressive episodes in
and disabling course of bipolar disorder. For patients with ADHD, and the existence of true
instance, they have been found to have more lifetime ADHD-bipolar disorder comorbidity can make this
affective episodes,40–43 more mixed episodes,45 more differential diagnosis difficult, some clear character-
manic episodes,46 more interpersonal violence,40,42 istics distinguish the two disorders.
more legal problems,40 more repeated grades,46 more
suicide attempts,40 more impulsivity,43 decreased Age of onset. By definition, ADHD symptoms must
quality of life,44,47 decreased social adjustment,47 and manifest prior to age 12 years, and data indicate that
a higher level of psychopathology.45 They also have the vast majority of individuals with ADHD show
more psychiatric comorbidities, especially substance symptoms by age 7 years. By contrast, the vast
abuse and panic disorder.40,41,44–46 majority of patients with bipolar disorder have dis-
Studies of bipolar comorbidity in adult cohorts with ease onset after age 12 years. For those with a true
ADHD are fewer, but the larger ones tend to agree on first-break mania in the early teen years, ADHD-
prevalence. The NCS-R, which used psychologist- bipolar disorder comorbidity may be a possibility.
administered semi-structured interviews to make
diagnoses in a large epidemiologic sample of patients Epidemiology. Most estimates put the prevalence of
with ADHD, found bipolar disorder in 19.4% of adults adult ADHD as at least double—and perhaps triple
with ADHD.1 The National Epidemiologic Survey on or quadruple—the prevalence of bipolar disorder in
Alcohol and Other Related Conditions (NESARC), the general population.
which was similar in scale and method, found a 12-
month prevalence of bipolar disorder of 22.7% in Disease course. By definition, ADHD is a non-cycli-
adults with ADHD.49 Two other studies—each involv- cal, chronic disease. Bipolar disorder is characterized
ing over 100 adult outpatients with ADHD, and with by episodes of depression, mania, or hypomania,
both disorders diagnosed by trained lay interviewers interspersed with periods of normal mood and ener-
administering the Structured Clinical Interview for gy.
DSM-IV—found lifetime rates of bipolar disorder of
18% and 18.7%.4,50 One study found a rate of comor- Mood. Although patients with ADHD can have
bid bipolar disorder of only 5.1%. This study was comorbid mood disorders, ADHD itself does not fea-
smaller (N = 79) and was based on a cohort of adult ture mood episodes. An ADHD patient may feel elat-
parents with ADHD who had two or more affected ed, depressed, or irritable at times, but a sustained
children.51 The aggregate of the research thus points change in mood from baseline lasting days to

Journal of Psychiatric Practice Vol. 20, No. 6 November 2014 435

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 ADULT ADHD VS. BIPOLAR DISORDER IN THE DSM-5 ERA

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