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Bipolar Disorders

By

William Coryell

, MD, University of Iowa Carver College of Medicine

Reviewed/Revised Oct 2023
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Topic Resources

Bipolar disorders are characterized by alternating episodes of mania Mania 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... read more and depression Depressive Disorders Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more , 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 are classified as

In cyclothymic disorder Cyclothymic Disorder Cyclothymic disorder is characterized by hypomanic and mini-depressive symptoms that last a few days, follow an irregular course, and are less severe than those in bipolar disorder; these symptom... read more , 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.

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 Etiology reference 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... read more ). 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

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.

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 Symptoms and signs references 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... read more ):

  • 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 Schizophrenia Schizophrenia is characterized by psychosis (loss of contact with reality), hallucinations (false perceptions), delusions (false beliefs), disorganized speech and behavior, flattened affect... read more . 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 Major depressive disorder (unipolar depressive disorder) Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more ; 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 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 Diagnosis references 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... read more ]). 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 Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism or pheochromocytoma Pheochromocytoma A pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. It causes persistent or paroxysmal hypertension. Diagnosis is by measuring catecholamine... read more . 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 ).

A review of substance use (especially of amphetamines Amphetamines Amphetamines are sympathomimetic drugs with central nervous system stimulant and euphoriant properties whose toxic adverse effects include delirium, hypertension, seizures, and hyperthermia... read more and cocaine Cocaine Cocaine is a sympathomimetic drug with central nervous system stimulant and euphoriant properties. High doses can cause panic, schizophrenic-like symptoms, seizures, hyperthermia, hypertension... read more ) 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.

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

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

Choice of pharmacotherapy Medications for Treatment of Bipolar Disorders Choice of pharmacologic agents to treat bipolar disorders can be difficult because all medications can potentially have significant adverse effects, drug interactions are common, and no medication... read more 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.

Other treatments

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 WJ: Ketamine in bipolar disorder: A review. Neuropsychiatr 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.

  • Treatment depends on the manifestations and their severity but typically involves mood stabilizers (eg, lithium, valproate, carbamazepine, lamotrigine) and/or second-generation antipsychotics (eg, aripiprazole, lurasidone, olanzapine, quetiapine, risperidone, ziprasidone, cariprazine).

Drugs Mentioned In This Article

Drug Name Select Trade
GOPRELTO, NUMBRINO
Eskalith, Eskalith CR, Lithobid
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR
Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite
Abilify, Abilify Asimtufii, Abilify Discmelt, Abilify Maintena, Abilify Mycite, Aristada
Latuda
Zyprexa, Zyprexa Intramuscular, Zyprexa Relprevv, Zyprexa Zydis
Seroquel, Seroquel XR
PERSERIS, Risperdal, Risperdal Consta, Risperdal M-Tab, Rykindo, UZEDY
Geodon
VRAYLAR
Ketalar
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