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Review
, 8 (1), 1

Bipolar Depression: A Major Unsolved Challenge

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Review

Bipolar Depression: A Major Unsolved Challenge

Ross J Baldessarini et al. Int J Bipolar Disord.

Abstract

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.

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References

    1. Acharya N, Rosen AS, Polzer JP, et al. Duloxetine: meta-analyses of suicidal behaviors and ideation in clinical trials for major depressive disorder. J Clin Psychopharmacol. 2006;26(6):587–594. doi: 10.1097/01.jcp.0000246216.26400.db. - DOI - PubMed
    1. Agosti V, Stewart JW. Hypomania with and without dysphoria: comparison of comorbidity and clinical characteristics of respondents from a national community sample. J Affect Disord. 2008;108(1–2):177–182. doi: 10.1016/j.jad.2007.09.006. - DOI - PubMed
    1. Ahmedani BK, Simon GE, Stewart C, et al. Healthcare contacts in the year before suicide death. J Gen Int Med. 2014;29(6):870–877. doi: 10.1007/s11606-014-2767-3. - DOI - PMC - PubMed
    1. Almeida OP, Hankey GJ, Yeap BB, Golledge J, Flicker L. Older men with bipolar disorder: clinical associations with early and late illness. Int J Geriatr Psychiatry. 2018;33(12):1613–1619. doi: 10.1002/gps.4957. - DOI - PubMed
    1. Altshuler LL, Sugar CA, McElroy SL, et al. Switch rates during acute treatment for bipolar II depression with lithium, sertraline, or the two combined: randomized, double-blind comparison. Am J Psychiatry. 2017;174(3):266–276. doi: 10.1176/appi.ajp.2016.15040558. - DOI - PubMed

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