Are Add-On Antidepressants Ineffective for Bipolar Depression?

Although depression is the leading cause of disability and death in bipolar illness, current medications are more effective for manic than depressive episodes. This pragmatic, placebo-controlled clinical trial from the NIMH-funded Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BP) examined whether antidepressants, taken with mood stabilizers, reduced depressive symptoms without increasing the risk for mania.

Of 2689 STEP-BD subjects with depression histories, 366 were enrolled in this trial and randomized to placebo or their choice of paroxetine (median dose, 30 mg) or bupropion (median dose, 300 mg). Study clinicians selected mood stabilizers (lithium, valproate, carbamazepine, or antipsychotics) and made other clinical decisions. Patients had multiple medical and psychiatric comorbidities (including substance abuse).

Antidepressant and placebo recipients had similar rates of durable recovery (8 weeks of euthymia; 24% vs. 27%), as well as response (32% vs. 38%), mood switching (10% vs. 11%), and discontinuation due to adverse events (12% vs. 9%). Neither concomitant psychosocial treatment nor bipolar type (1 or 2) altered response levels.