Bipolar disorders are characterized by alternating episodes of mania and depression, although many patients have a predominance of one or the other. Exact cause is unknown, but heredity, changes in the level of brain neurotransmitters, and psychosocial factors may be involved. Diagnosis is based on history. Treatment consists of mood-stabilizing medications, sometimes with psychotherapy.
Bipolar disorders usually begin in the teens, 20s, or 30s (see also Bipolar Disorder in Children and Adolescents). Lifetime prevalence is approximately 2% (1).
Bipolar disorders are classified as
Bipolar I disorder: Defined by the presence of at least one full-fledged (ie, causes marked impairment in social or occupational function or includes delusions) manic episode and usually depressive episodes. Incidence is similar in men and women (2).
Bipolar II disorder: Defined by the presence of major depressive episodes with at least one hypomanic episode but no full-fledged manic episodes. Incidence is somewhat higher for females (3).
Substance-/medication-induced bipolar disorder: Defined by the presence of a mood disturbance consistent with mania that develops during or soon after an exposure, intoxication, or withdrawal from a substance (eg, , corticosteroids) that is capable of producing such symptoms.
Bipolar and related disorder due to another medical condition: Defined by the presence of a mood disturbance consistent with mania that is caused by a medication condition (eg, Cushing syndrome, traumatic brain injury) and does not occur exclusively during an episode of delirium.
Unspecified bipolar disorder: Disorders with clear bipolar features that do not meet the specific criteria for other bipolar disorders
In cyclothymic disorder, patients have prolonged (> 2-year) periods that include both hypomanic and depressive episodes; however, these episodes do not meet the specific criteria for a bipolar or major depressive disorder.
(See also Overview of Mood Disorders.)
General references
1. Merikangas KR, Akiskal HS, Angst J, et al: Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 64(5):543-552, 2007. doi: 10.1001/archpsyc.64.5.543. Erratum in: Arch Gen Psychiatry 64(9):1039, 2007. PMID: 17485606
2. Diflorio A, Jones I: Is sex important? Gender differences in bipolar disorder. Int Rev Psychiatry 22(5):437-452, 2010. doi: 10.3109/09540261.2010.514601. PMID: 21047158
3. Baldassano CF, Marangell LB, Gyulai L, et al: Gender differences in bipolar disorder: retrospective data from the first 500 STEP-BD participants. Bipolar Disord 7(5):465-470, 2005. doi: 10.1111/j.1399-5618.2005.00237.x
Etiology of Bipolar Disorders
The exact cause of bipolar disorder is unknown. Heredity plays a significant role (1). There is also evidence of dysregulation of the neurotransmitters serotonin, norepinephrine, and dopamine.
Psychosocial factors may be involved. Stressful life events are often associated with initial development of symptoms and later exacerbations, although cause and effect have not been established.
Certain medications and substances can trigger exacerbations in some patients with bipolar disorder; these include
Sympathomimetics (eg, , amphetamines)
Corticosteroids
Certain antidepressants (eg, tricyclics, noradrenergic reuptake inhibitors)
Etiology reference
1. Gordovez FJA, McMahon FJ: The genetics of bipolar disorder. Mol Psychiatry 25(3):544-559, 2020. doi: 10.1038/s41380-019-0634-7
Symptoms and Signs of Bipolar Disorders
Bipolar disorder begins with an acute phase of symptoms of depression or mania, followed by a repeating course of remission and relapse. Remissions are often complete, but many patients have residual symptoms, and for some, the ability to function at work is severely impaired. Relapses are discrete episodes of more intense symptoms that are manic, depressive, hypomanic, or a mixture of depressive and manic features.
Episodes last anywhere from a few weeks to 3 to 6 months; depressive episodes typically last longer than manic or hypomanic ones.
Cycles—time from onset of one episode to that of the next—vary in length among patients. Some patients have infrequent episodes, perhaps only a few over a lifetime, whereas others have rapid-cycling forms (usually defined as ≥ 4 episodes/year). Only a minority alternate back and forth between mania and depression with each cycle; in most, one or the other predominates.
Patients may attempt or complete suicide. Lifetime incidence of suicide in patients with bipolar disorder is estimated to be at least 20 to 30 times that of the general population (1).
Mania
A manic episode is defined as ≥ 1 week of a persistently elevated, expansive, or irritable mood and persistently increased goal-directed activity or a noticeable increase of energy plus ≥ 3 additional symptoms (or ≥ 4 if the mood is only irritable) (2):
Inflated self-esteem or grandiosity
Decreased need for sleep
Greater talkativeness than usual
Flight of ideas or racing of thoughts
Distractibility
Increased goal-directed activity or psychomotor agitation
Excessive involvement in activities with high potential for painful consequences (eg, buying sprees, foolish business investments)
Manic patients may be inexhaustibly, excessively, and impulsively involved in various pleasurable, high-risk activities (eg, gambling, dangerous sports, promiscuous sexual activity) without insight into possible harm. Symptoms are so severe that they cannot function in their primary roles (eg, occupation, school, family life). Unwise investments, spending sprees, and other personal choices may have irreparable consequences.
Patients in a manic episode may be exuberant and flamboyantly or colorfully dressed and often have an authoritative manner with a rapid, unstoppable flow of speech. Patients may make clang associations (new thoughts that are triggered by word sounds rather than meaning). Easily distracted, patients may constantly shift from one theme or endeavor to another. However, they tend to believe they are in their best mental state.
Lack of insight and an increased capacity for activity often lead to intrusive behavior and can be a dangerous combination. Interpersonal friction results and may cause patients to feel that they are being unjustly treated or persecuted. As a result, patients may become a danger to themselves or to other people. Accelerated mental activity is experienced as racing thoughts by patients and is observed as flights of ideas by the physician.
Manic psychosis is a more extreme manifestation, with psychotic symptoms that may be difficult to distinguish from schizophrenia. Patients may have extreme grandiose or persecutory delusions (eg, of being Jesus or being pursued by the FBI), occasionally with hallucinations. Activity level increases markedly; patients may race about and scream, swear, or sing. Mood lability increases, often with increasing irritability. Full-blown delirium (delirious mania) may appear, with complete loss of coherent thinking and behavior.
Hypomania
A hypomanic episode is a less extreme variant of mania involving a distinct episode that lasts ≥ 4 days with behavior that is distinctly different from the patient’s usual nondepressed self and that includes ≥ 3 of the additional symptoms listed above under mania.
During the hypomanic period, mood brightens, the need for sleep decreases as energy noticeably increases, and psychomotor activity accelerates. For some patients, hypomanic periods are adaptive because they produce high energy, creativity, confidence, and supernormal social functioning. Many do not wish to leave the pleasurable, euphoric state. Some function quite well, and functioning is not markedly impaired. However, in some patients, hypomania manifests as distractibility, irritability, and labile mood, which the patient and others find less attractive.
Depression
A major depressive episode in patients with bipolar disorder has features typical of major depression; the episode must include ≥ 5 of the following during the same 2-week period, and one of them must be depressed mood or loss of interest or pleasure and, with the exception of suicidal thoughts or attempts, all symptoms must be present nearly every day:
Depressed mood most of the day
Markedly diminished interest or pleasure in all or almost all activities for most of the day
Significant (>5%) weight gain or loss or decreased or increased appetite
Insomnia (often sleep-maintenance insomnia) or hypersomnia
Psychomotor agitation or retardation observed by others (not self-reported)
Fatigue or loss of energy
Feelings of worthlessness or excessive or inappropriate guilt
Diminished ability to think or concentrate or indecisiveness
Recurrent thoughts of death or suicide, a suicide attempt, or specific plan for suicide
Psychotic features are more common in bipolar depression than in unipolar depression.
Mixed features
An episode of mania or hypomania is designated as having mixed features if ≥ 3 depressive symptoms are present for most days of the episode. This condition is often difficult to diagnose and may shade into a continuously cycling state; the prognosis is then worse than that in a pure manic or hypomanic state.
Risk of suicide during mixed episodes is particularly high.
Symptoms and signs references
1. Plans L, Barrot C, Nieto E, et al: Association between completed suicide and bipolar disorder: A systematic review of the literature. J Affect Disord 242:111-122, 2019. doi: 10.1016/j.jad.2018.08.054
2. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, pp 140-141.
Diagnosis of Bipolar Disorders
Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision criteria
Thyroxine (T4) and thyroid-stimulating hormone (TSH) level to screen for hyperthyroidism
Exclusion of stimulant abuse clinically or by blood or urine toxicology screening
Routine laboratory tests (eg, complete blood cell count, basic metabolic panel) to rule out other general medical conditions
Diagnosis of bipolar I disorder requires meeting the DSM-5-TR criteria for a manic episode as described above, plus a history of remission and relapse (1). The manic episode may have been preceded by or followed by hypomanic or major depressive episodes.
Diagnosis of bipolar II disorder requires meeting the DSM-5-TR criteria for at least one hypomanic episode as well as at least one major depressive episode [2]). The symptoms must be severe enough to markedly impair social or occupational functioning or to require hospitalization to prevent harm to self or others.
Some patients who present with depressive symptoms may have previously experienced hypomania or mania but do not report it unless they are specifically questioned. Skillful questioning may reveal morbid signs (eg, excesses in spending, impulsive sexual escapades, stimulant abuse), although such information is more likely to be provided by relatives. A structured inventory such as the Mood Disorder Questionnaire may be useful. All patients must be asked gently but directly about suicidal ideation, plans, or activity.
Similar acute manic or hypomanic symptoms may result from stimulant abuse, treatment with corticosteroids or dopamine agonists, or general medical disorders such as hyperthyroidism or pheochromocytoma. Patients with hyperthyroidism typically have other physical symptoms and signs, but thyroid function testing (T4 and TSH levels) is a reasonable screen for new patients. Patients with pheochromocytoma have marked intermittent or sustained hypertension; if hypertension is absent, testing for pheochromocytoma is not indicated. Other disorders less commonly cause symptoms of mania, but depressive symptoms may occur in a number of disorders (see table Some Causes of Symptoms of Depression and Mania).
A review of substance use (especially of amphetamines and ) and blood or urine toxicology screening can help identify such causes. However, because substance use may simply have triggered an episode in a patient with bipolar disorder, seeking evidence of symptoms (manic or depressive) not related to substance use is important.
Some patients with schizoaffective disorder have manic symptoms, but such patients have psychotic features that may persist beyond the abnormal mood episodes.
Patients with bipolar disorder may also have anxiety disorders (eg, social phobia, panic attacks, obsessive-compulsive disorders), possibly confusing the diagnosis.
Diagnosis references
1. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, pp 140-151.
2. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, pp 151-160.
Treatment of Bipolar Disorders
(See also Medications for Treatment of Bipolar Disorder.)
Mood stabilizers (eg, , certain antiseizure medications), a second-generation antipsychotic, or both
Support and psychotherapy
Treatment of bipolar disorder usually has 3 phases:
Acute: To stabilize and control the initial, sometimes severe manifestations
Continuation: To attain full remission
Maintenance or prevention: To keep patients in remission
Although most patients with hypomania can be treated as outpatients, severe mania or depression often requires inpatient management.
Pharmacotherapy for bipolar disorder
Medications for bipolar disorder include
Mood stabilizers: and certain antiseizure medications
These medications are used alone or in combination for all phases of treatment, although at different dosages (1, 2).
Choice of pharmacotherapy for bipolar disorder can be difficult because all medications have significant adverse effects, drug interactions are common, and no medication is universally effective. Selection should be based on what has previously been effective and well-tolerated in a given patient. If the patient has not previously been given medications to treat bipolar disorder (or medication history is unknown), choice is based on the patient’s medical history (vis-à-vis the adverse effects of the specific mood stabilizer) and the severity of symptoms.
Specific antidepressants (eg, selective serotonin3).
Other treatments
Electroconvulsive therapy (ECT) is sometimes used for depression refractory to treatment and is also effective for mania (4).
Phototherapy can be useful in treating depressive symptoms of seasonal (with autumn-winter depression and spring-summer hypomania) or nonseasonal bipolar I or bipolar II disorder. It is probably most useful as augmentative therapy.
Transcranial magnetic stimulation, which is sometimes used to treat severe, resistant depression, has also proven effective in bipolar depression (5).
Education and psychotherapy
Enlisting the support of loved ones is crucial to preventing major episodes.
Group therapy is often recommended for patients and their partner; there, they learn about bipolar disorder, its social sequelae, and the central role of mood stabilizers in treatment.
Individual psychotherapy may help patients better cope with problems of daily living and adjust to a new way of identifying themselves.
Patients, particularly those with bipolar II disorder, may not adhere to mood-stabilizer regimens because they believe that these medications make them less alert and creative. The physician can explain that decreased creativity is relatively uncommon because mood stabilizers usually provide opportunity for a more even performance in interpersonal, scholastic, professional, and artistic pursuits.
Patients should be counseled to avoid stimulants and alcohol, to minimize sleep deprivation, and to recognize early signs of relapse.
If patients tend to be financially extravagant, finances should be turned over to a trusted family member. Patients with a tendency to sexual excesses should be given information about conjugal consequences (eg, divorce) and infectious risks of promiscuity, particularly AIDS.
Support groups (eg, the Depression and Bipolar Support Alliance [DBSA]) can help patients by providing a forum to share their common experiences and feelings.
Treatment references
1. Yatham LN, Kennedy SH, et al: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord 20(2):97-170, 2018. doi: 10.1111/bdi.12609
2. Goodwin GM, Haddad PM, Ferrier IN, et al: Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol 30(6):495-553, 2016. doi: 10.1177/0269881116636545
3. Wilkowska A, Szałach Ł, Cubała WJNeuropsychiatr Dis Treat 16:2707-2717, 2020. doi: 10.2147/NDT.S282208
4. Perugi G, Medda P, Toni C, et al: The role of electroconvulsive therapy (ECT) in bipolar disorder: Effectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic features. Curr Neuropharmacol 15(3):359-371, 2017. doi: 10.2174/1570159X14666161017233642
5. Lefaucheur JP, Aleman A, Baeken C: Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol 131(2):474-528, 2020. doi: 10.1016/j.clinph.2019.11.002. Erratum in: Clin Neurophysiol 131(5):1168-1169, 2020. PMID: 31901449
Key Points
Bipolar disorder is a cyclic condition that involves episodes of mania with or without depression (bipolar I) or hypomania plus depression (bipolar II).
Bipolar disorder markedly impairs the ability to function at work and to interact socially, and risk of suicide is significant; however, mild manic states (hypomania) are sometimes adaptive because they can produce high energy, creativity, confidence, and supernormal social functioning.
Length and frequency of cycles vary among patients; some patients have only a few over a lifetime, whereas others have ≥ 4 episodes/year (rapid-cycling forms).
Only a few patients alternate back and forth between mania and depression during each cycle; in most cycles, one or the other predominates.
Diagnosis is based on clinical criteria, but stimulant use disorder and general medical disorders (such as hyperthyroidism or pheochromocytoma) must be ruled out by examination and testing.
