Bipolar disorders

• Published in: The Lancet (British edition) 2020-12, Vol.396 (10265), p.1841-1856
• Main Authors: McIntyre, Roger S, Berk, Michael, Brietzke, Elisa, Goldstein, Benjamin I, López-Jaramillo, Carlos, Kessing, Lars Vedel, Malhi, Gin S, Nierenberg, Andrew A, Rosenblat, Joshua D, Majeed, Amna, Vieta, Eduard, Vinberg, Maj, Young, Allan H, Mansur, Rodrigo B
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Affective disorders; Analysis; Anticonvulsants - therapeutic use; Antidepressants; Antidepressive Agents - therapeutic use; Antimanic Agents - therapeutic use; Antipsychotic Agents - therapeutic use; Antipsychotics; Anxiety; Bipolar disorder; Bipolar Disorder - classification; Bipolar Disorder - drug therapy; Bipolar Disorder - genetics; Bipolar Disorder - psychology; Carbamazepine; Carbamazepine - therapeutic use; Cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - mortality; Child; Child Abuse - psychology; Children; Comorbidity; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Depressive Disorder, Major - psychology; Diagnostic systems; Drug therapy; Environmental Exposure - adverse effects; Epidemiology; Health care; Health services; Heritability; Humans; Income; Inflammation; Lamotrigine; Lamotrigine - therapeutic use; Lithium; Lithium - therapeutic use; Mania - drug therapy; Mania - psychology; Mental depression; Mental disorders; Mental health; Metabolic pathways; Mitochondria; Mood; Morbidity; Mortality; Neuronal-glial interactions; Pathogenesis; Physicians; Plastic foam; Primary care; Schizophrenia; Signal transduction; Signs and symptoms; Social interactions; Stabilizers (agents); Suicide; Suicide - prevention & control; Suicide - psychology; Suicides & suicide attempts; Valproic acid; Valproic Acid - therapeutic use; Young Adult
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(20)31544-0

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10–20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly