Depression in bipolar disorder (BD) patients presents major clinical challenges. As the predominant psychopathology even in treated BD, depression is associated not only with excess morbidity, but also mortality from co-occurring general-medical disorders and high suicide risk. In BD, risks for medical disorders including diabetes or metabolic syndrome, and cardiovascular disorders, and associated mortality rates are several-times above those for the general population or with other psychiatric disorders. The SMR for suicide with BD reaches 20-times above general-population rates, and exceeds rates with other major psychiatric disorders. In BD, suicide is strongly associated with mixed (agitated-dysphoric) and depressive phases, time depressed, and hospitalization. Lithium may reduce suicide risk in BD; clozapine and ketamine require further testing. Treatment of bipolar depression is far less well investigated than unipolar depression, particularly for long-term prophylaxis. Short-term efficacy of antidepressants for bipolar depression remains controversial and they risk clinical worsening, especially in mixed states and with rapid-cycling. Evidence of efficacy of lithium and anticonvulsants for bipolar depression is very limited; lamotrigine has long-term benefit, but valproate and carbamazepine are inadequately tested and carry high teratogenic risks. Evidence is emerging of short-term efficacy of several modern antipsychotics (including cariprazine, lurasidone, olanzapine-fluoxetine, and quetiapine) for bipolar depression, including with mixed features, though they risk adverse metabolic and neurological effects.
Keywords: Bipolar disorder; Depression; Disability; Morbidity; Mortality; Suicide; Treatment.
Conflict of interest statement
The authors declare that they have no competing interests.
[Antipsychotics in bipolar disorders].Encephale. 2004 Sep-Oct;30(5):417-24. doi: 10.1016/s0013-7006(04)95456-5. Encephale. 2004. PMID: 15627046 Review. French.
Pharmacological treatment of adult bipolar disorder.Mol Psychiatry. 2019 Feb;24(2):198-217. doi: 10.1038/s41380-018-0044-2. Epub 2018 Apr 20. Mol Psychiatry. 2019. PMID: 29679069 Review.
Efficacy and tolerability of treatments for bipolar depression.J Affect Disord. 2015 Sep 1;183:258-62. doi: 10.1016/j.jad.2015.05.016. Epub 2015 May 19. J Affect Disord. 2015. PMID: 26042634
Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.Pharmacopsychiatry. 2014 Mar;47(2):43-52. doi: 10.1055/s-0033-1363258. Epub 2014 Feb 18. Pharmacopsychiatry. 2014. PMID: 24549862 Review.
Agitated "unipolar" depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy.J Affect Disord. 2005 Apr;85(3):245-58. doi: 10.1016/j.jad.2004.12.004. J Affect Disord. 2005. PMID: 15780694