Bipolar disorder commonly develops during a depressive episode, and as patients are more often in a depressive state than (hypo) mania, clinicians often treat depressed patients. However, therapeutic options for bipolar depression are currently limited compared with those for acute mania, and its clinical treatment remains unclear. Clinical guidelines recommend mood stabilizers and atypical antipsychotics, such as lithium, lamotrigine, quetiapine, and olanzapine, as the first-line treatment for depressive episodes in bipolar disorder. The use of antidepressants, which used to be commonly administered for bipolar depression, is controversial, and they have become less common due to concern over risks for manic switch, destabilization, and rapid cycling. Pharmacotherapy for bipolar disorder has changed markedly compared with approximately 20 years ago. However, antidepressants are widely used to treat acute bipolar depression in clinical settings, and may be effective for some patients. Although there are risks, antidepressant treatment, especially SSRIs or bupropion, may be effective in combination with atypical antipsychotics or mood stabilizers, as recommended by the International Society for Bipolar Disorders (ISBD) Task Force. Recent meta-analyses also demonstrated that modern antidepressants combined with mood stabilizers had a small but significant effect and did not increase the risk of manic switch during short-term treatment of bipolar depression. Several studies have reported that adjunctive antidepressant therapy is associated with a lower rate of rehospitalization and relapse of mood episodes without increasing the risk of new (hypo) manic episodes. Indeed, there is insufficient evidence for antidepressant use for bipolar depression, but it may be helpful rather than harmful in some cases. Antidepressants should be prescribed appropriately for bipolar depression after considering the clinical picture, diagnosis, specifiers, comorbidities, and drug classes, instead of discussing the pros and cons of antidepressants as a whole.
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