Bipolar disorder in adults: Clinical features

Authors
Trisha Suppes, MD
Victoria E Cosgrove, PhD
Section Editor
Paul Keck, MD
Deputy Editor
David Solomon, MD
Disclosures: Trisha Suppes, MD Grant/Research Support: Elan Pharma International Limited [mood disorders];
Pfizer Inc [mood disorders (Zipriasidone)]; Sunovion Pharmaceuticals, Inc [mood disorders (Lurasidone)].
Consultant/Advisory Boards: Sunovion Pharmaceuticals, Inc [mood disorders (Lurasidone)]; H. Lundbeck A/S [mood
disorders (Asenapine)]; Astra Zeneca [mood disorders (Quetiapine)]. Other Financial Interests: Jones and Bartlett
[royalties]; Medscape Education [honoraria]; Omnia-Provo Education Collaborative, Inc [honoraria]; Astra Zeneca
[honoraria (Quetiapine)]; American Psychiatric Association [honoraria]; International Society of Bipolar Disorders
[honoraria]; Columbia Sunovion Pharmaceuticals, Inc [honoraria (Lurasidone)]. Victoria E Cosgrove, PhD Nothing to
disclose. Paul Keck, MD Consultant/Advisory Boards: Sunovian (bipolar depression [lurasidone]); Alkermes
(schizophrenia [long-acting injectable aripiprazole]); Shire (binge eating disorder [lisdexamfetamine dimesylate]);
Forest (bipolar mania [cariprazine]). Patent Holder: No. 6,387,956 (Methods of treating obsessive-compulsive
spectrum disorder [tramadol]).David Solomon, MD Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Dec 2014. | This topic last updated: Nov 19, 2014.
INTRODUCTION Bipolar disorder frequently disrupts mood, energy, sleep, cognition, and
behavior [1], and patients thus struggle to maintain employment and interpersonal relationships [24]. Pharmacotherapy within the context of a positive therapeutic alliance is central to minimizing
morbidity and the risk of suicide.
This topic reviews the clinical features of bipolar disorder in adults. The assessment, diagnosis, and
treatment of bipolar disorder in adults are discussed separately, as are the clinical features and
diagnosis of bipolar disorder in children and adolescents, geriatric patients, and patients with rapid
cycling (ie, four or more mood episodes in a 12-month period):
(See "Bipolar disorder in adults: Assessment and diagnosis".)
(See "Bipolar disorder in adults: Pharmacotherapy for acute depression".)
(See "Bipolar disorder in adults: Pharmacotherapy for acute mania and hypomania".)
(See "Bipolar disorder in adults: Maintenance treatment".)
(See "Bipolar disorder in children and adolescents: Epidemiology, pathogenesis, clinical
manifestations, and course".)
(See "Bipolar disorder in children and adolescents: Assessment and diagnosis".)
(See "Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and
diagnosis".)
(See "Rapid cycling bipolar disorder: Epidemiology, pathogenesis, clinical features, and
diagnosis".)

DEFINITION OF BIPOLAR DISORDER Bipolar disorder is a mood disorder that is characterized

by episodes of mania (table 1), hypomania (table 2), and major depression (table 3) [1]. The
subtypes of bipolar disorder include bipolar I and bipolar II. Patients with bipolar I disorder
experience manic episodes and nearly always experience major depressive and hypomanic
episodes (table 4). Bipolar II disorder is marked by at least one hypomanic episode, at least one
major depressive episode, and the absence of manic episodes. Additional information about the
diagnosis of bipolar disorder is discussed separately. (See "Bipolar disorder in adults: Assessment
and diagnosis".)
CLINICAL PRESENTATION Bipolar disorder can present with mania (table 1), hypomania (table
2), major depression (table 3), or mixed features (mood episodes that are accompanied by
symptoms of the opposite polarity) [1,5]. The severity of these syndromes varies widely across
patients, as well as within individual patients, and subsyndromal symptoms are common [6-8]. In
addition, some symptomatic patients remit and become euthymic, while other patients transition
immediately from one type of syndrome to another (eg, from major depression to mania) without an
intervening period of euthymia [9].
The mood episode at onset of bipolar disorder is usually major depression [10]. In a study of 2308
patients, the first lifetime episode was [11]:
Major depression in 54 percent
Mania in 22 percent
Mixed (concurrent symptoms of major depression and mania) in 24 percent
Prodrome Although many studies indicate that prodromal signs and symptoms such as
irritability, anxiety, mood lability (mood swings), agitation, aggressiveness, sleep disturbance, and
hyperactivity may precede onset of diagnosable bipolar disorder, the proportion of patients who
experience a prodrome varies widely across studies [12-14]. In addition, the same features can
occur during the prodrome of other psychiatric disorders.
Mania Manic episodes (table 1) involve clinically significant changes in mood, behavior, energy,
sleep, and cognition (table 5) [5]. It is not known whether the symptom profile of mania is consistent
across multiple episodes within the same patient. The intensity of manic episodes varies widely
across patients.
Abnormally elevated, irritable, and labile mood is a core symptom required to diagnose mania [1].
Classic mania is marked by an unusually good, euphoric, or high mood, which may be
accompanied by disinhibition (eg, wearing garish clothes or disrobing in public), disregard for social
boundaries, expansiveness, and a relentless pursuit of stimulation and social activities (eg, acting
flirtatious, renewing old friendships, or lengthy telephone calls with strangers) [15]. The elevated
mood may have an infectious quality that initially engages others; however, patients often become
offensive due to their insensitivity to the needs of others.
Another core diagnostic symptom of mania is persistently increased energy and goal-directed
activity [1]. Increased planning and activity is typically marked by impulsivity, poor judgement, and
disregard for risks [16]. Examples include taking on new and foolish business ventures,
unaffordable spending sprees, sexual infidelity or numerous sexual encounters with strangers, and
driving recklessly. In addition, patients are often unable to complete the many tasks or projects that
are started. Two independent nationally representative surveys in the United States and a third

survey in Australia, which identified individuals with mania in the general population, all found that
increased goal-directed activity was the most commonly endorsed symptom [17,18].
Manic patients generally have an exaggerated sense of wellbeing and self-confidence, which may
extend to grandiosity of psychotic proportions (see 'Psychosis' below) [1]. As an example, some
patients believe they have a special relationship with God or celebrities, or possess talents that
surpass the abilities of others. Among individuals with mania in the general population, increased
self-esteem and grandiosity are the least commonly endorsed symptom [17,18].
In addition, mania is typically marked by a decreased need for sleep; this is distinguished from
insomnia, which involves the inability to sleep despite feeling tired [1]. Manic patients may feel wellrested after a few (eg, three) hours of sleep, or feel energetic and wired despite not sleeping for
days [15].
Common cognitive symptoms of mania include increased mental activity, racing thoughts,
distractibility, and difficulty distinguishing between relevant and irrelevant thoughts; these symptoms
result in flight of ideas (abrupt changes from one topic to another that are based upon
understandable associations) [1]. In addition, patients may not recall events that occur during manic
episodes [19].
Manic speech is generally loud, pressured or accelerated, and difficult to interrupt, and may be
accompanied by jokes, singing, clanging (choosing words based upon sounds rather than
meaning), and dramatic gesticulations. Irritable patients often make hostile comments, swear more
than usual, or go off on angry tirades [15].
As a result, psychosocial functioning is markedly impaired, and hospitalization is often required to
protect manic patients and prevent behavior leading to painful consequences (eg, financial ruin, job
loss, divorce, and assaulting others) [11,20]. One impediment to treatment is that many patients,
particularly those who are psychotic, have little insight into their psychopathology and functional
impairment, and are impervious to feedback from others [21-23].
The course of illness in mania is generally marked by a sudden onset, and episodes progress
quickly over a few days. The duration of manic episodes ranges from weeks to months; in a
prospective observational study of 246 manic episodes, recovery from 25 percent of the episodes
occurred within 4 weeks of onset, and recovery from 50 percent and 75 percent of the episodes
occurred within 7 and 15 weeks of onset [24]. Resolution of mania typically does not involve
residual symptoms.
Hypomania Hypomanic episodes (table 2) are characterized by changes in mood, behavior,
energy, sleep, and cognition that are similar to those of mania, but less severe [1,25]. Examples
include the following:
Self-esteem may be inflated during hypomania, but never reaches the point of delusional
grandiosity that can occur during mania.
Although mental overactivity and flight of ideas can occur in either hypomania or mania,
thought form is more organized in hypomania.
Thinking in hypomania is often quick and creative, and leads to productive increases in goaldirected activities, whereas mania is marked by racing thoughts that are disconnected and
lead to aimless overactivity.

Hypomanic speech can be loud and rapid, but typically is easier to interrupt than manic
speech.
Psychosocial functioning in hypomania is either improved or mildly impaired, whereas mania
markedly impairs functioning.
Risk-taking behavior in hypomania is mild to moderate, but in mania is severe.
By definition, hypomania never necessitates hospitalization; by contrast, mania frequently
does.
It is not known whether the symptom profile of hypomania is consistent across multiple episodes
within the same patient.
The course of hypomania is such that it generally begins suddenly and progresses quickly over one
to two days. Episodes typically resolve within several weeks; a prospective observational study of
126 hypomanic episodes found that recovery from 25 percent of the episodes occurred within two
weeks of onset, and recovery from 50 percent and 75 percent of the episodes occurred within three
and six weeks [24].
Major depression Episodes of major depression (table 3) involve clinically significant changes in
mood, behavior, energy, sleep, and cognition [5]. The intensity of episodes varies widely.
Similar to unipolar major depression, bipolar major depression is generally characterized by
dysphoria, as well as slowing in the pace of mental and physical activity (eg, speech is slow and
soft, and output reduced) [5]. Interest in pleasurable activities (eg, sex) is minimal, energy is low,
and memory and concentration are impaired. Appetite is typically diminished and accompanied by
weight loss; however, some patients may manifest increased appetite and weight gain. Although
behavior is generally slow, some patients are agitated (eg, unable to sit still or wringing their hands).
Sleep disturbances (insomnia or hypersomnia) often occur in bipolar depression [26], as do feelings
of worthlessness and excessive guilt [5], and suicidal thoughts and behavior. (See 'Suicide' below.)
Other clinical features of major depression include poor eye contact, poor hygiene, unkempt
appearance, feelings of hopelessness and helplessness, rumination and indecisiveness, negative
and nihilistic thoughts, somatic symptoms (eg, pain), and impaired psychosocial functioning [5].
Additional information about the clinical manifestation of major depression is discussed elsewhere.
(See "Unipolar depression in adults: Assessment and diagnosis".)
Depressive symptoms are more common in bipolar disorder than manic/hypomanic symptoms,
especially in bipolar II patients [27,28]:
A prospective observational study of 146 bipolar I patients who were followed for an average
of 13 years examined the mean percent of time that patients had any
depressive, manic/hypomanic, or mixed (concurrent depressive
and manic/hypomanic) symptoms; pure depressive symptoms were present for 32 percent of
follow-up, pure manic/hypomanic symptoms for 9 percent, and mixed symptoms for 6 percent
[7].
A comparable study of 86 bipolar II patients who were followed prospectively for an average
of 13 years found that pure depressive symptoms were present for 50 percent of follow-up,
pure hypomanic symptoms for 1 percent, and mixed symptoms for 2 percent [8].

The symptom profile of bipolar major depression is often inconsistent across multiple episodes
within a particular patient. A study of 583 patients with at least two prospectively observed
depressive episodes found that within an individual patient, there was little consistency in the
specific symptoms or sets of symptoms from one episode to the next [29].
The course of illness in bipolar major depression varies, and onset may be sudden or develop
slowly over weeks to months. Episodes typically last several months. A prospective observational
study of 373 bipolar major depressive episodes found that recovery from 25 percent of the episodes
occurred within 6 weeks of onset, and recovery from 50 percent and 75 percent of the episodes
occurred within 15 and 35 weeks [24]. Residual symptoms are common among patients who
otherwise recover.
Mixed features Episodes of bipolar mania, hypomania, and major depression can be
accompanied by symptoms of the opposite polarity, and are referred to as mood episodes with
mixed features (eg, major depression with mixed features) [1]. Other terms used in the literature
include mixed episodes, mixed states, mixedmania/hypomania, and
dysphoric mania/hypomania [5,30,31].
Manic or hypomanic episodes with mixed features are characterized by episodes that meet full
criteria for mania (table 1) or hypomania (table 2), and at least three of the following symptoms
during most days of the episode [1]:
Depressed mood
Diminished interest or pleasure in most activities
Psychomotor retardation
Low energy
Excessive guilt or thoughts of worthlessness
Recurrent thoughts about death or suicide, or suicide attempt
Major depressive episodes with mixed features are characterized by episodes that meet full criteria
for major depression (table 3), and at least three of the following symptoms during most days of the
episode [1]:
Elevated or expansive mood
Inflated self-esteem or grandiosity
More talkative than usual or pressured speech
Flight of ideas (abrupt changes from one topic to another that are based upon
understandable associations) or racing thoughts
Increased energy or goal-directed activity
Excessive involvement in pleasurable activities that have a high potential for painful
consequences (eg, buying sprees or sexual indiscretions)
Decreased need for sleep
Mood episodes with mixed features may present de novo or evolve from episodes of pure mania,
hypomania, or major depression. Episodes with mixed features may last weeks to months and can
remit or evolve into major depression. It is unusual for mixed episodes to transition to mania.

Mixed features occur frequently [32-37]. One review estimated that among bipolar patients, mixed
features occur in 20 to 70 percent [25].
Compared with bipolar patients without mixed features, patients with mixed features are at greater
risk for suicidal ideation and behavior, and comorbid anxiety disorders and substance use disorders
[31]. In addition, response to treatment is often poorer in mood episodes with mixed features than in
pure bipolar major depression or pure mania [24,31,38]. As an example, a randomized trial found
that among 36 manic patients who were assigned to lithium, response was worse in patients (n =
14) with depressive symptoms than patients with pure mania [32,39].
Psychosis Psychotic features such as delusions (false, fixed beliefs) and hallucinations (false
sensory perceptions) can occur during manic, major depressive, and mixed episodes [40];
disorganized thinking and behavior can occur as well. Psychotic features may be more common
during mania than bipolar major depression [5,41]. By definition, psychosis does not occur in
hypomania [1]. Delusions may involve grandiosity, as well as persecutory, sexual, religious, or
political themes; hallucinations are typically auditory in nature [5,42].
Bipolar mood episodes frequently include psychosis:
A pooled analysis of 33 studies (5973 bipolar patients) found a lifetime history of at least one
psychotic symptom in 61 percent of patients and that delusions were more common than
hallucinations [5].
A subsequent, nationwide register based study of 14,529 bipolar patients found that the
lifetime prevalence of psychotic mania and psychotic depression was 19 and 15 percent [43].
It is not clear if psychotic features are associated with a more severe long-term course of illness
[5,40,43-46]. Additional information about psychosis is discussed separately. (See "Clinical
manifestations, differential diagnosis, and initial management of psychosis in adults", section on
'Clinical manifestations'.)
COMORBIDITY Most bipolar patients have at least one comorbid psychiatric or general medical
illness, and many patients have multiple co-occurring illnesses. Comorbidity in pediatric, geriatric,
and rapid cycling bipolar disorder is discussed separately. (See "Bipolar disorder in children and
adolescents: Epidemiology, pathogenesis, clinical manifestations, and course", section on
'Comorbidity' and "Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and
diagnosis", section on 'Comorbidity' and "Rapid cycling bipolar disorder: Epidemiology,
pathogenesis, clinical features, and diagnosis", section on 'Comorbidity'.)
Psychiatric disorders Patients with bipolar disorder commonly manifest comorbid psychiatric
disorders, including:
Anxiety disorders
Substance use disorders
Attention deficit hyperactivity disorder (ADHD)
Eating disorders
Intermittent explosive disorder
Personality disorders

Most bipolar patients have at least one other psychiatric disorder. A large, nationally representative
survey in the United States found that in bipolar patients, the lifetime prevalence of at least one cooccurring disorder was 92 percent [47]. By contrast, the lifetime prevalence of at least one
psychiatric disorder in the general population was 46 percent [48].
In addition, many bipolar patients suffer multiple comorbid psychiatric disorders:
A large, cross-national, epidemiologic survey in 11 countries found that among individuals
with bipolar disorder, the lifetime prevalence of three or more comorbid disorders was 44
percent [49].
An epidemiologic study in the United States found that among individuals with bipolar
disorder, the lifetime prevalence of three or more comorbid disorders was 70 percent [47]. By
contrast, the lifetime prevalence of three or more disorders in the general population was 17
percent [48].
Anxiety disorders Anxiety disorders that can occur in patients with bipolar disorder include:
Agoraphobia
Generalized anxiety disorder
Panic attacks and panic disorder
Specific phobia
Social anxiety disorder (social phobia)
Epidemiologic studies show that patients with bipolar disorder frequently suffer comorbid anxiety
disorders [47,50]:
A survey in 11 countries found that the lifetime prevalence of any anxiety disorder among
individuals with bipolar disorder was 63 percent [49].
A study from the United States found that among individuals with bipolar disorder, the lifetime
prevalence of anxiety disorders was 75 percent [47]. By contrast, the lifetime prevalence of
anxiety disorders in the general population was 29 percent [48].
In bipolar patients, the most common comorbid anxiety disorders are panic attacks, specific phobia,
social anxiety disorder, and generalized anxiety disorder.
Compared with bipolar patients without a history of comorbid anxiety disorders, patients with
comorbid anxiety have a worse course of illness [51], including:
Earlier age of onset of bipolar disorder [52,53]
Decreased likelihood of recovery from mood episodes [51,54]
More recurrent mood episodes [51,53-56]
Increased prevalence of substance use disorders [51,52,55]
Poorer psychosocial functioning [54,55] and quality of life [54,56]
Poorer insight [51]
Greater impulsivity [57,58]
More suicide attempts [52,53,55,56,59-61]
Anxiety disorders are discussed separately.

Substance use disorders Epidemiologic studies show that patients with bipolar disorder
frequently suffer comorbid substance use disorders (eg, alcohol, benzodiazepines, and cannabis)
[50,62,63]:
A survey in 11 countries found that the lifetime prevalence of any substance use disorder
among individuals with bipolar I disorder was 52 percent, and in bipolar II disorder was 37
percent [49].
A study from the United States found that among individuals with bipolar I disorder, the
lifetime prevalence of substance use disorders was 60 percent, and in bipolar II disorder was
40 percent [47]. By contrast, the lifetime prevalence of substance use disorders in the United
States general population was 15 percent [48].
Studies of bipolar patients in clinical settings indicate that comorbid alcohol and drug use disorders
are associated with a worse course of illness, including [64-66]:
More mood symptoms [67,68]
More hospitalizations [69,70]
Decreased likelihood of recovery from mood episodes [68,71]
More recurrent mood episodes [64,72,73]
Neurocognitive impairment [74]
Poorer psychosocial functioning [71,75] and quality of life [76,77]
Higher levels of aggressiveness [64,78] and more arrests [72,79]
More suicide attempts [71,80,81]
Substance use disorders are discussed separately.
Attention deficit hyperactivity disorder Epidemiologic studies show that patients with bipolar
disorder frequently have a history of ADHD:
A survey in 11 countries found that the lifetime prevalence of ADHD among individuals with
bipolar disorder was 20 percent [49].
A study from the United States found that among individuals with bipolar disorder, the lifetime
prevalence of ADHD was 31 percent [47]. By contrast, the lifetime prevalence of ADHD in the
general population was 8 percent [48].
Compared with bipolar patients without a history of comorbid ADHD, patients with comorbid ADHD
have a worse course of illness, including:
Earlier age at onset of bipolar disorder [82-85]
Decreased likelihood of recovery from mood episodes [82]
More recurrent mood episodes [82,83,85]
Increased prevalence of anxiety and substance use disorders [82,84]
Poorer psychosocial functioning [83,84]
History of legal problems and violence [82,85]
More suicide attempts [82]
Adult ADHD is discussed separately. (See "Adult attention deficit hyperactivity disorder in adults:
Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis".)

Eating disorders The prevalence of comorbid eating disorders appears to be greater among
bipolar patients treated in clinical settings, compared with bipolar patients identified in the general
population. In addition, comorbid eating disorders are associated with a worse course of illness.
A clinical study of 875 patients with bipolar disorder found that a lifetime history of at least one
comorbid eating disorder was present in 14 percent, including [86]:
Binge eating disorder 9 percent of patients
Bulimia nervosa 5 percent
Anorexia nervosa 3 percent
A second study of bipolar patients in clinical settings (n = 717) found that binge eating disorder was
present in 9 percent [87].
By contrast, a large, nationally representative epidemiologic study of the general population in the
United States found the following lifetime prevalence rates [88]:
Binge eating disorder 2.8 percent
Bulimia nervosa 1.0 percent
Anorexia nervosa 0.6 percent
Compared with bipolar patients without a history of comorbid eating disorders, patients with
comorbid eating disorders have a worse course of illness, including:
Earlier age of onset of bipolar disorder [86,89]
More recurrent mood episodes [86,89]
Lifetime history of psychosis [87]
Increased prevalence of anxiety and substance use disorders [86,87,89,90]
More suicide attempts [86,87,89]
Eating disorders are discussed separately. (See "Eating disorders: Overview of epidemiology,
diagnosis, and course of illness" and "Eating disorders: Overview of treatment".)
Intermittent explosive disorder Epidemiologic studies show that patients with bipolar disorder
frequently suffer comorbid intermittent explosive disorder:
A survey in 11 countries found that the lifetime prevalence of intermittent explosive disorder
among individuals with bipolar disorder was 24 percent [49].
One study from the United States found that among individuals with bipolar disorder, the
lifetime prevalence of intermittent explosive disorder was 29 percent [47]. By contrast, the
lifetime prevalence of intermittent explosive disorder in the general population was 5 percent
[48].
Intermittent explosive disorder is discussed separately. (See "Intermittent explosive disorder in
adults: Epidemiology, clinical features, assessment, and diagnosis" and"Intermittent explosive
disorder in adults: Treatment and prognosis".)
Personality disorders Personality disorders are more prevalent in bipolar disorder than the
general population. A nationally representative survey in the United States found that the

prevalence of the following disorders was greater in bipolar patients than the general population
[91]:
Any personality disorder (51 percent of bipolar patients versus 9 percent of the general
population)
Any Cluster A (paranoid, schizoid, and schizotypal) personality disorder (13 versus 6
percent)
Any Cluster B (antisocial, borderline, histrionic, and narcissistic) personality disorder (15
versus 2 percent)
Any Cluster C (avoidant, dependent, obsessive compulsive, and passive aggressive)
personality disorder (22 versus 6 percent)
Borderline personality disorder (15 percent of bipolar patients versus 1 percent of the general
population)
In addition, bipolar patients in clinical settings commonly present with personality disorders [92]. A
meta-analysis of 13 studies found that in 1101 outpatients and inpatients with bipolar disorder, at
least one personality disorder was present in 42 percent [93]. Compared to bipolar patients without
a personality disorder, patients with comorbid personality disorders have a worse course of illness,
including:
Earlier age of onset of bipolar disorder [92]
Decreased likelihood of recovery from mood episodes [92,94,95]
Poorer psychosocial functioning [92]
More suicide attempts [92]
In addition, personality traits such as novelty seeking and harm avoidance are more common in
bipolar patients than healthy controls [96].
The diagnosis and treatment of personality disorders are discussed separately. (See "Personality
disorders".)
General medical illnesses Bipolar patients are at increased risk for comorbid general medical
illnesses [50,97]. In a large, nationally representative epidemiologic study in the United States that
included 1548 individuals with bipolar disorder, at least one general medical condition was present
in the past year in 32 percent, and five or more conditions were present in 10 percent [98]. For most
of the general medical disorders that were examined, the annual prevalence rate was higher in
bipolar individuals than nonbipolar individuals; as an example, the prevalence of angina in bipolar
persons was 18 percent and in nonbipolar persons 6 percent.
General medical disorders that appear to be more prevalent among bipolar patients than persons
without the disorder include [97-111]:
Arthritis
Back pain
Cardiovascular disease (angina pectoris, atherosclerosis, or myocardial infarction)
Chronic obstructive pulmonary disease (COPD)
Diabetes
Dyslipidemia

Gastritis and stomach ulcer

Headache
HIV infection
Hypertension
Hypothyroidism
Liver disease other than cirrhosis (eg, hepatitis C)
Metabolic syndrome and obesity
In clinical settings, most bipolar patients have coexisting general medical conditions. A study from
the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) found that among
3766 patients, at least one comorbid illness was observed in 59 percent [112]. In other clinical
studies of bipolar disorder, the mean number of co-occurring general medical illnesses ranged from
2.4 to 3.4 [76,109,113,114]. The number and severity of general medical illnesses may increase
with age and duration of bipolar disorder [114].
Compared with bipolar patients without a history of comorbid general medical conditions, patients
with co-occurring conditions have a worse course of illness, including:
Decreased probability of recovery from depressive episodes [104]
More recurrent mood episodes [98,115-117]
Increased prevalence of anxiety and substance use disorders [98,101,104,108,117,118]
Poorer psychosocial functioning [98,104,108]
More suicide attempts [118,119]
Increased all cause mortality [120]
As an example, a national registry study in Sweden found that bipolar patients (n >6600) died
approximately nine years earlier than the population [120]. Premature mortality in bipolar disorder
was related to a two- to three-fold increase in mortality from coronary heart disease, chronic
obstructive pulmonary disease, diabetes mellitus, and influenza or pneumonia. In addition, mortality
from chronic diseases (coronary heart disease, chronic obstructive pulmonary disorder, and
diabetes) was lower for bipolar patients who were already diagnosed with chronic disease than
bipolar patients without a prior diagnosis. Thus, identifying and treating chronic diseases in bipolar
patients may reduce premature mortality.
NEUROCOGNITIVE FUNCTION Multiple studies using standardized tests demonstrate that
neuropsychological function in bipolar patients is impaired during euthymia as well as mood
episodes [121-124]. As an example, a meta-analysis of 45 observational studies compared 1423
euthymic bipolar patients with 1524 healthy controls, and found several deficits in patients, including
impaired [125]:
Attention
Verbal memory
Executive function (eg, planning, concept or set shifting, and response inhibition)
Information processing speed

A subsequent meta-analysis of individual patient data (31 studies, 2876 euthymic bipolar patients
and healthy controls) that controlled for age, sex, and intelligence quotient found that these deficits
were clinically small to moderate [126].
Neuropsychological deficits can occur in both bipolar I disorder and bipolar II disorder [127,128],
appear early in the course of illness [129-131], persist over time and remain stable (rather than
progressing) [132-134], are associated with impaired psychosocial functioning [132,135], and
overlap with impairments found in schizophrenia and schizoaffective disorder [136-139] as well as
unipolar major depression [140,141].
However, neurocognitive function in bipolar disorder ranges from normal to global impairment [142].
In addition, intelligence quotient appears to be largely preserved [121,127,141].
Cognitive impairment in pediatric and geriatric bipolar disorder is discussed separately.
(See "Bipolar disorder in children and adolescents: Epidemiology, pathogenesis, clinical
manifestations, and course", section on 'Neurocognitive function' and "Geriatric bipolar disorder:
Epidemiology, clinical features, assessment, and diagnosis", section on 'Cognitive impairment'.)
Social cognition Bipolar disorder is associated with impaired social cognition or competence
[143-145]. Social cognition involves the ability to:
Recognize thoughts, beliefs, and intentions in oneself and others (often referred to as theory
of mind)
Identify basic emotions such as happiness, sadness, fear, anger, disgust, and surprise in
others (emotion processing)
Make decisions by weighing choices associated with variable rewards and punishments
A meta-analysis of 20 observational studies (650 euthymic bipolar patients and 607 healthy
controls) found statistically significant, clinically large deficits in theory of mind, as well as clinically
small to moderate impairments in emotion processing [143].
Creativity The hypothesis that bipolar disorder is associated with creativity is longstanding but
not established [5,146,147]. Limited evidence for the association includes studies that found higher
scores on creativity measures in bipolar patients than controls and disproportionately high rates of
bipolar disorder in creative individuals or occupations [148-151]. As an example, a case control
study based upon Swedish population registries identified bipolar patients, healthy siblings of
patients, and controls [152]. Bipolar patients were more likely to have worked in creative
professions than controls (OR 1.4, 95% CI 1.2-1.5), and siblings were also more likely to have
worked in creative professions than controls (OR 1.3, 95% CI 1.2-1.5).
SUICIDE
Deaths A review estimated that approximately 10 to 15 percent of bipolar patients die by suicide
[153], and many studies indicate that the rate of suicide deaths in patients is greater than the rate in
the general population:
A meta-analysis of 14 observational studies (3700 patients with bipolar disorder) found that
the observed number of suicides was 15 times the expected value [154].

A subsequent study using Swedish national registries found that among female bipolar
patients (n = 8808), mortality from suicide was 22 times greater than the rate in the general
population, and for male patients (n = 6578) was 15 times greater [155].
A subsequent study found that in 220 bipolar patients followed for up to 44 years, the rate of
completed suicide was 12 times greater than the rate in the general population [156].
Two risk factors for completed suicide in bipolar disorder were identified in a meta-analysis of 13
observational studies (847 bipolar patients who committed suicide and 16,831 who did not) [59]:
History of attempted suicide
Hopelessness
Attempts Suicide attempts are common in bipolar disorder:
In a retrospective study of 3536 patients, a lifetime history of at least one suicide attempt was
found in 27 percent [157].
A prospective study of 1556 patients followed for up to two years found that suicide was
attempted by 3 percent [158].
A prospective study of 4360 patients (mean follow-up 16 months) found that suicide was
attempted by 4 percent; among the 174 patients who attempted suicide, 32 percent made
multiple attempts [159].
Based upon a meta-analysis of 23 observational studies (2213 bipolar patients who attempted
suicide and 5120 patients who did not), suicide attempts are associated with [59]:
Marital status of never married (single)
History of having been physically or sexually abused
Early age of onset of bipolar disorder (eg, <25 years)
Depressive symptoms (see 'Major depression' above)
Mixed features (see 'Mixed features' above)
Progressive, increasing severity of depressive and manic episodes
Comorbid psychiatric disorders, including anxiety disorders, drug abuse, and alcohol abuse
(see 'Psychiatric disorders' above)
Family history of suicide death
A subsequent prospective study found that suicide attempts were associated with prior attempts
and depressive symptoms [158].
Additional information about suicidal ideation and behavior is discussed separately. (See "Suicidal
ideation and behavior in adults".)
VIOLENT BEHAVIOR Violent behavior appears to be more common in bipolar patients than the
general population, but at least some of the elevated risk is due to comorbidity (eg, substance use
disorders) [160]. Evidence linking violent behavior to bipolar disorder includes the following:
A national registry study found that violent crime (convictions for homicide, assault, robbery,
arson, or threats) was greater in bipolar patients (n = 3743) than matched general population
controls (n = 37,429) (8 versus 4 percent) [160]. However, the risk was largely confined to
patients with comorbid substance abuse; violent crime in bipolar disorder plus substance

abuse (n = 795) was greater compared with bipolar disorder alone (n = 2948) (21 versus 5
percent).
A nationally representative survey in the United States (n >49,000) found that violent
behavior (eg, forcing someone to have sex, physically assaulting others, or robbing someone)
was more prevalent in bipolar I individuals (n = 1411) and bipolar II individuals (n = 494),
compared with individuals with no lifetime psychiatric disorder (25 and 14 versus 1 percent)
[161]. In addition, interpersonal violence was higher in bipolar I and bipolar II patients with
comorbid substance use, anxiety, and personality disorders than bipolar patients with no
comorbidity. Many of these findings were replicated in a subsequent study using the same
dataset [162].
A meta-analysis of nine observational studies found that aggressive behavior occurred in
more bipolar patients (n >6000) than general population controls (n >112,000) (10 versus 3
percent; odds ratio 4); however, heterogeneity across studies was large [160]. A subsequent
prospective study, which adjusted for sociodemographic characteristics, victimization (abuse)
in childhood, negative life events, and poor social support, also found that bipolar individuals
were four times more likely to perpetrate physical violence than the general population [163].
Other epidemiologic studies indicate that among bipolar patients, comorbid intermittent explosive
disorder occurs in approximately 25 to 30 percent. (See 'Intermittent explosive disorder' above.)
Aggressive behavior may be more common in bipolar disorder than other psychiatric disorders
[164,165]. A four-year prospective observational study found that physical aggression (eg, using
physical force to express anger) was persistently greater in bipolar patients (n = 227), compared
with patients with other psychiatric disorders (n = 75) [166]. In addition, aggressive behavior in
bipolar patients was more common during mood episodes.
Aggression in bipolar patients may be elevated even during periods of euthymia. A study found
greater levels of aggression (assessed with a standardized scale) in 24 euthymic bipolar patients in
stable treatment, compared with 38 matched controls [167].
Assessment and management of agitation and aggressive behavior are discussed separately.
(See "Assessment and management of the acutely agitated or violent adult".).
LEGAL PROBLEMS Manic patients often incur criminal justice problems. A nationally
representative survey in the United States identified 623 individuals who had suffered an episode of
mania in the past three years; during the episode, 11 percent were arrested [168]. The probability of
arrest was increased in patients with prior arrests, psychosocial impairment, and substance use
disorders, as well as patients whose race was nonwhite. However, its not clear whether the rate of
legal involvement in manic patients is greater than the rate in the general population.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The
Basics and Beyond the Basics. The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Bipolar disorder (The Basics)")
Beyond the Basics topics (see "Patient information: Bipolar disorder (manic depression)
(Beyond the Basics)")
SUMMARY
Diagnosis of bipolar mood episodes and disorders is generally made according to the
American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5). (See "Bipolar disorder in adults: Assessment and diagnosis".)
Bipolar disorder can present with mania (table 1), hypomania (table 2), or major depression
(table 3). The mood episode at onset of bipolar disorder is usually major depression.
(See 'Clinical presentation' above.)
Mania and bipolar major depression are often accompanied by psychotic features, such as
delusions (false, fixed beliefs) and hallucinations (false sensory perceptions); by definition,
psychosis does not occur in hypomania. (See 'Psychosis' above.)
Most patients with bipolar disorder have at least one comorbid psychiatric illness; common
co-occurring disorders include (see 'Psychiatric disorders' above):
Anxiety disorders
Substance use disorders
Attention deficit hyperactivity disorder (ADHD)
Eating disorders
Intermittent explosive disorder
Personality disorders
Patients with bipolar disorder are at increased risk for comorbid general medical illnesses.
(See 'General medical illnesses' above.)
Multiple studies using standardized tests in bipolar patients demonstrate that neurocognitive
function is impaired during asymptomatic phases as well as mood episodes; deficits include
impaired attention, verbal memory, executive function, and information processing speed.
(See 'Neurocognitive function' above.)
Approximately 10 to 15 percent of bipolar patients die by suicide, which is greater than the
rate of suicide in the general population. Risk factors for completed suicide include
hopelessness and a history of attempted suicide. (See 'Deaths' above.)
Suicide attempts are common in bipolar disorder and associated with marital status of never
married (single), history of physical or sexual abuse, early age of onset of bipolar disorder (eg,
<25 years), depressive symptoms, mixed states, progressive severity of depressive and manic
episodes, comorbid psychiatric disorders, and family history of suicide death.
(See 'Attempts' above.)
Violent behavior appears to be more common in bipolar patients than the general population,
but at least some of the risk is due to comorbidity (eg, substance use disorders). In addition,
aggressive behavior may be more common in bipolar disorder than other psychiatric
disorders. (See 'Violent behavior' above.)
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