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Bipolar disorder in adults: Clinical features

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Bipolar disorder in adults: Clinical features Authors Trisha Suppes, MD Victoria E Cosgrove, PhD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last updated: Ago 5, 2013. INTRODUCTION Bipolar disorder frequently disrupts mood, energy, sleep, cognition, and behavior [1], and patients thus struggle to maintain employment and interpersonal relationships [2-4]. 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, mixed episodes, 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 and mixed episodes (concurrent mania and major depression) 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 and mixed 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 states (concurrent manic/hypomanic and depressive symptoms) [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. A study found that among 2308 patients, the first lifetime episode was [10]: Major depression in 54 percent Mania in 22 percent Mixed in 24 percent Prodrome Although many studies indicate that prodromal signs and symptoms such as irritability, anxiety, mood Section Editor Paul Keck, MD Deputy Editor David Solomon, MD

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Bipolar disorder in adults: Clinical features

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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 [11-13]. 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. Elevated, irritable, and labile mood is a core symptom of manic episodes [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) [14]. 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. Manic patients generally have an exaggerated sense of well being and self-confidence, which may extend to grandiosity of psychotic proportions [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. (See 'Psychosis' below.) 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 well rested after a few (eg, three) hours of sleep, or feel energetic and wired despite not sleeping for days [14]. 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 [15]. 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 [14]. Increased planning and goal directed activity in mania is typically marked by poor judgement and disregard for risks [1]. 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. 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) [10,16]. 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 [17-19]. The course of illness in mania is generally marked by a sudden onset, and episodes progress quickly over a few days [1]. 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 [20]. Resolution of mania typically does not involve residual symptoms [1]. 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 [1,21]. 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 goal directed activities, whereas mania is marked by racing thoughts that are disconnected and lead to aimless

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Bipolar disorder in adults: Clinical features

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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 [1]. 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 [20]. Resolution of mania typically does not involve residual symptoms; however, it is estimated that 5 to 15 percent of patients with hypomania transition to mania [1]. 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 [22], 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 "Clinical manifestations and diagnosis of depression", section on 'Clinical presentation'.) Depressive symptoms are more common in bipolar disorder than manic/hypomanic symptoms, especially in bipolar II patients [23,24]: 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 [25]. The course of illness in bipolar major depression varies, and onset may be sudden or develop slowly over weeks to months [1]. 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

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Bipolar disorder in adults: Clinical features

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recovery from 50 percent and 75 percent of the episodes occurred within 15 and 35 weeks [20]. Residual symptoms are common among patients who otherwise recover [1]. Mixed mania and depression Bipolar patients can manifest co-occurring symptoms of mania/hypomania and major depression, which are sometimes referred to as mixed episodes, mixed states, mixed mania/hypomania, or dysphoric mania/hypomania [5,26,27]. Mixed episodes are characterized by a period of time lasting at least one week during which full criteria for a manic (table 1) and major depressive episode (except duration) (table 3) are met concurrently [1]. Mixed states (or mixed mania or dysphoric mania) are marked by simultaneous symptoms of mania and depression that do not meet symptom threshold criteria for manic and major depressive episodes. Recognizing a mixed state can be difficult if the patient presents with a preponderance of manic or depressive symptoms. Mixed states occur frequently [28-33]. A review estimated that in bipolar patients, mixed states occur in 20 to 70 percent [21]. In addition, response to treatment is often poorer in mixed states than pure major depression or pure mania [20,34]. 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 [28,35]. Mixed episodes and states may present de novo or evolve from mania, hypomania, or major depression [1]. The episodes may last weeks to months and can remit or evolve into major depression. It is unusual for mixed episodes to transition to mania. Psychosis Psychotic features such as delusions (false, fixed beliefs) and hallucinations (false sensory perceptions) can occur during manic, major depressive, and mixed episodes [36]; disorganized thinking and behavior can occur as well. Psychotic features may be more common during mania than bipolar major depression [5,37]. 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 [5,38]. 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 [39]. It is not clear if psychotic features are associated with a more severe long-term course of illness [5,36,39-42]. Additional information about psychosis is discussed separately. (See "Overview of psychosis", section on 'Psychosis'.) 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 Common comorbid psychiatric disorders include: Anxiety disorders Substance use disorders Attention hyperactivity disorder Intermittent explosive disorder Eating disorders 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 co-occurring disorder was 92

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Bipolar disorder in adults: Clinical features

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percent [43]. By contrast, the lifetime prevalence of at least one psychiatric disorder in the general population was 46 percent [44]. 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 [45]. 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 [43]. By contrast, the lifetime prevalence of three or more disorders in the general population was 17 percent [44]. Anxiety disorders Anxiety disorders that can occur in patients with bipolar disorder include: Agoraphobia Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Panic attacks and panic disorder Posttraumatic stress disorder (PTSD) Specific phobia Social phobia Epidemiologic studies show that patients with bipolar disorder frequently suffer comorbid anxiety disorders [43,46]: A survey in 11 countries found that the lifetime prevalence of any anxiety disorder among individuals with bipolar disorder was 63 percent [45]. A study from the United States found that among individuals with bipolar disorder, the lifetime prevalence of anxiety disorders was 75 percent [43]. By contrast, the lifetime prevalence of anxiety disorders in the general population was 29 percent [44]. In bipolar patients, the most common comorbid anxiety disorders are panic attacks, specific and social phobias, and generalized anxiety disorder. Compared to bipolar patients without a history of comorbid anxiety disorders, patients with comorbid anxiety have a worse course of illness [47], including: Earlier age of onset of bipolar disorder [48,49] Decreased likelihood of recovery from mood episodes [47,50] More recurrent mood episodes [47,49-52] Increased prevalence of substance use disorders [47,48,51] Poorer psychosocial functioning [50,51] and quality of life [50,52] Poorer insight [47] Greater impulsivity [53,54] More suicide attempts [48,49,51,52,55-57] 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) [46,58,59]: 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 [45]. 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 [43]. By contrast, the lifetime prevalence of substance use disorders in the United States general population was 15 percent [44]. Studies in clinical settings also show that many bipolar patients have comorbid alcohol and drug use disorders that

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Bipolar disorder in adults: Clinical features

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are associated with a worse course of illness, including [60-62]: More mood symptoms [63,64] More hospitalizations [65,66] Decreased likelihood of recovery from mood episodes [64,67] More recurrent mood episodes [60,68,69] Neurocognitive impairment [70] Poorer psychosocial functioning [67,71] and quality of life [72,73] Higher levels of aggressiveness [60,74] and more arrests [68,75] More suicide attempts [67,76,77] Substance use disorders are discussed separately. Attention deficit hyperactivity disorder Epidemiologic studies show that patients with bipolar disorder frequently have a history of attention deficit hyperactivity disorder (ADHD): A survey in 11 countries found that the lifetime prevalence of ADHD among individuals with bipolar disorder was 20 percent [45]. A study from the United States found that among individuals with bipolar disorder, the lifetime prevalence of ADHD was 31 percent [43]. By contrast, the lifetime prevalence of ADHD in the general population was 8 percent [44]. Compared to 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 [78-81] Decreased likelihood of recovery from mood episodes [78] More recurrent mood episodes [78,79,81] Increased prevalence of anxiety and substance use disorders [78,80] Poorer psychosocial functioning [79,80] History of legal problems and violence [78,81] More suicide attempts [78] Adult ADHD is discussed separately. (See "Adult attention deficit hyperactivity disorder".) 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 [45]. One study from the United States found that among individuals with bipolar disorder, the lifetime prevalence of intermittent explosive disorder was 29 percent [43]. By contrast, the lifetime prevalence of intermittent explosive disorder in the general population was 5 percent [44]. 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".) Eating disorders 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 [82]: Binge eating disorder 9 percent of patients Bulimia nervosa 5 percent Anorexia nervosa 3 percent By contrast, a large, nationally representative epidemiologic study of the general population in the United States found the following lifetime prevalence rates [83]:

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Binge eating disorder 2.8 percent Bulimia nervosa 1.0 percent Anorexia nervosa 0.6 percent Compared to 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 [82,84] More recurrent mood episodes [82,84] Increased prevalence of anxiety and substance use disorders [82,84,85] More suicide attempts [82,84] Eating disorders are discussed separately. (See "Eating disorders: Epidemiology, pathogenesis, clinical features, and course of illness" and "Eating disorders: Overview of treatment".) Personality disorders Personality disorders are more prevalent in bipolar disorder than the general population. In an epidemiologic study from the United States, the prevalence for each of the following was greater in bipolar patients than the general population [86]: 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) Comorbid personality disorders in bipolar patients are also common in clinical settings, based upon a review of 21 studies that found the prevalence of any personality disorder ranged from 12 to 70 percent [87]. 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 [87] Decreased likelihood of recovery from mood episodes [87-89] Poorer psychosocial functioning [87] More suicide attempts [87] Personality disorders are discussed separately. (See "Personality disorders".) General medical illnesses Patients with bipolar disorder are at increased risk for comorbid general medical illnesses [46,90]. 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 [91]. 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 [90-104]: Arthritis Back pain Cardiovascular disease (angina pectoris, atherosclerosis, or myocardial infarction) Chronic obstructive pulmonary disease (COPD) Diabetes Dyslipidemia Gastritis and stomach ulcer

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Headache HIV infection Hypertension Hypothyroidism Liver disease other than cirrhosis (eg, hepatitis C) Metabolic syndrome and obesity In clinical settings, most bipolar patients have co-existing 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 [105]. In other clinical studies of bipolar disorder, the mean number of co-occurring general medical illnesses ranged from 2.4 to 3.4 [72,102,106,107]. The number and severity of general medical illnesses may increase with age and duration of bipolar disorder [107]. Compared to 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 [97] More recurrent mood episodes [91,108-110] Increased prevalence of anxiety and substance use disorders [91,94,97,101,110,111] Poorer psychosocial functioning [91,97,101] More suicide attempts [111,112] Increased all cause mortality [113] As an example, a national registry study in Sweden found that bipolar patients (N >6600) died approximately nine years earlier than the rest of the population [113]. Premature mortality in bipolar disorder was due in part to a twoto 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 less among bipolar patients with a prior diagnosis of these chronic diseases than bipolar patients without a prior diagnosis. Thus, evaluation for and treatment of chronic diseases in bipolar patients may possibly 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 [114-117]. In a meta-analysis of 45 observational studies that compared 1423 euthymic bipolar patients with 1524 healthy controls (age, sex, education, and premorbid intelligence quotient [IQ] were comparable for the two groups), statistically significant and clinically moderate to large deficits were observed in patients, including impaired [118]: Attention Verbal memory Executive function (eg, working memory, verbal fluency, and concept or set shifting) Information processing speed A second analysis of 17 studies that compared neuropsychological performance in 443 first-degree relatives of the bipolar patients with 797 controls found significant but clinically small deficits in verbal memory and executive functions among the family members [118]. Neuropsychological deficits appear early in the course of illness [119-121], occur in both bipolar I disorder and bipolar II disorder [122,123], are associated with impaired psychosocial functioning [124], and overlap with impairments found in schizophrenia and schizoaffective disorder [125-128], as well as unipolar major depression [129,130]. However, IQ appears to be largely preserved in bipolar disorder [114,122,130]. 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 [131,132]. Social cognition involves the ability to:

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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 [131]. Creativity The hypothesis that bipolar disorder is associated with creativity is long standing but not established [5]. 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 [133-136]. As an example, a case control study based upon Swedish population registries identified bipolar patients, healthy siblings of patients, and controls [137]. 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 [138], 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 [139]. 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 [140]. 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 [141]. 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) [55]: 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 [142]. A prospective study of 1556 patients followed for up to two years found that suicide was attempted by 3 percent [143]. 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 [144]. Based upon a meta-analysis of 23 observational studies (2213 bipolar patients who attempted suicide and 5120 who did not), suicide attempts are associated with [55]: Marital status of never married (single) History of having been physical or sexual abused Early age of onset of bipolar disorder (eg, <25 years) Depressive symptoms (see 'Major depression' above) Mixed states (see 'Mixed mania and depression' above) Progressive, increasing severity of depressive and manic episodes Comorbid psychiatric disorders, including anxiety disorders, drug abuse, and alcohol abuse (see 'Psychiatric

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disorders' above) Family history of suicide death A subsequent prospective study found that suicide attempts were associated with prior attempts and depressive symptoms [143]. 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). Evidence linking violent behavior to bipolar disorder includes the following: A study using Swedish national registries 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) [145]. 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). In a nationally representative survey in the United States (N = 49,093), violent behavior (eg, forcing someone to have sex, getting into fights, physically assaulting others, or robbing someone) was more prevalent in bipolar I individuals (N = 1411) and bipolar II individuals (N = 494), compared to individuals with no lifetime psychiatric disorder (25 and 14 versus 1 percent) [146]. 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 [147]. A meta-analysis of nine observational studies found that aggressive behavior occurred in more bipolar patients (N = 6383) than general population controls (N = 112,944) (10 versus 3 percent); heterogeneity across studies was large [145]. 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 [148,149]. A study found that physical aggression (eg, using physical force to express anger) was greater in bipolar patients (N = 255), compared to patients with other psychiatric disorders (N = 85) [150]. 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 [151]. Assessment and management of agitation and aggressive behavior are discussed separately. (See "Assessment and management of the acutely agitated or violent adult".). 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 10th 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)")

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Bipolar disorder in adults: Clinical features

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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, Fourth Edition, Text Revision (DSM-IV-TR). (See "Bipolar disorder in adults: Assessment and diagnosis".) Bipolar disorder can present with mania (table 1), hypomania (table 2), major depression (table 3), or mixed states (concurrent manic/hypomanic and depressive symptoms). 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: Anxiety disorders Substance use disorders Attention hyperactivity disorder Intermittent explosive disorder Eating disorders Personality disorders (See 'Psychiatric disorders' above.) 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 Information processing speed (See 'Neurocognitive function' above.) Approximately 10 to 15 percent of bipolar patients die by suicide, and the rate of suicide deaths in patients is greater than the rate 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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Bipolar disorder in adults: Clinical features

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Bipolar disorder in adults: Clinical features

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GRAPHICS DSM-IV-TR diagnostic criteria for mania


A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, feels rested after only 3 hours of sleep) 3) More talkative than usual or pressure to keep talking 4) Flight of ideas or subjective experience that thoughts are racing 5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The symptoms do not meet criteria for a mixed episode. D. The mood disturbance 1) is sufficiently severe to cause marked impairment in occupational functioning, usual social activities, or relationships with others, 2) necessitates hospitalization to prevent harm to self or others, or 3) has psychotic features. E. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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Bipolar disorder in adults: Clinical features

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DSM-IV-TR diagnostic criteria for hypomania


A. A distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, that is clearly different from the usual nondepressed mood. B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, feels rested after only 3 hours of sleep) 3) More talkative than usual or pressure to keep talking 4) Flight of ideas or subjective experience that thoughts are racing 5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The episode 1) is not severe enough to cause marked impairment in social or occupational functioning, 2) does not necessitate hospitalization, and 3) does not have psychotic features. F. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism). Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, ECT, light therapy) should not count toward a diagnosis of bipolar II disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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Bipolar disorder in adults: Clinical features

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DSM-IV-TR diagnostic criteria for major depression


A. Five (or more) of the following symptoms have been present during the same 2-week period, and represent a change from previous functioning. At least one of the symptoms is either depressed mood or loss of interest or pleasure.
(Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.) Depressed mood most of the day, nearly every day (or alternatively can be irritable mood in children and adolescents) Markedly diminished interest or pleasure in all, or almost all, activities, nearly every day Significant weight loss while not dieting, weight gain, or decrease or increase in appetite Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or excessive or inappropriate guilt nearly every day Diminished ability to think or concentrate, or indecisiveness, nearly every day Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

B. The symptoms do not meet criteria for a Mixed Episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of substance or a general medical condition. E. The symptoms are not better accounted for by Bereavement, ie, after the loss of a loved one, the symptoms persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. American Psychiatric Association, Washington, DC 2000.

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Bipolar disorder in adults: Clinical features

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Comparison of DSM-5 criteria for bipolar I disorder and bipolar II disorder


Bipolar I disorder
Manic episode(s) Hypomanic episode(s) Major depressive episode(s) Mixed features Anxious distress Rapid cycling Psychotic features Catatonia Yes Commonly occur, but not required Usually occur, but not required May occur May occur May occur May occur May occur Yes May occur May occur May occur May occur May occur

Bipolar II disorder
No Yes

Data from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifrth Edition, American Psychiatric Association, Arlington, VA, 2013.

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Bipolar disorder in adults: Clinical features

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Frequency of specific symptoms during mania


Symptom
Mood* Irritability Euphoria Expansiveness Lability ("mood swings") Depression Cognitive Flight of ideas, racing thoughts Distractibility, poor concentration Grandiosity, over confident Confusion, disorientation, impaired memory Activity and behavior Hyperactivity Increased speech output Rapid, pressured speech Decreased need for sleep, insomnia Increased libido Violent, assaultive behavior Religiosity Extravagant spending sprees Nudity, sexual exposure Pronounced regression Catatonia 90 89 88 83 51 47 39 32 29 28 24 76 75 73 29 71 63 60 49 46

Weighted mean (percent)

* Based upon a pooled analysis of 16 studies (1121 manic patients). Based upon a pooled analysis of 13 studies (968 manic patients). Based upon a pooled analysis of 16 studies (1857 manic patients). Data from: 1. Goodwin F, Jamison K. Manic-Depressive Illness: Bipolar disorders and recurrent depression, 2nd ed, Oxford University Press, New York 2007. 2. Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2009 on the treatment of acute mania. World J Biol Psychiatry 2009; 10:255.

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