Pharmacological Treatment of Bipolar Depression: What are the Current and Emerging Options?

Depression accounts for the predominant burden associated with bipolar disorder. The identification and management of bipolar depression are challenging, since bipolar depression differs from unipolar depression, responding poorly to traditional antidepressants, which may also induce a switch to hypomania/mania, mixed states and/or cause rapid cycling. Current treatment options for bipolar depression are limited and guidelines vary greatly in their recommendations, reflecting gaps and inconsistencies in the current evidence base. Moreover, some treatment options, such as quetiapine and olanzapine-fluoxetine, although clearly efficacious, may be associated with adverse cardiometabolic side effects, which can be detrimental to the long-term physical health and well-being of patients, increasing the likelihood of treatment non-adherence and relapse. Evidence for some more recent therapeutic options, including lurasidone and cariprazine, suggests that patients' symptoms can be effectively managed without compromising their physical health. In addition, novel agents targeting alternative neurotransmitter pathways and inflammatory processes (such as ketamine and N-acetyl cysteine) are emerging as promising potential options for the treatment of bipolar depression in the future.