Bipolar Depression: A Major Unsolved Challenge
Harold Saive
Bipolar Depression: A Major Unsolved Challenge
https://link.springer.com/article/10.1186/s40345-019-0160-1
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.
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