Episodes of depression are frequent causes of disability among those with bipolar disorder. However, the effectiveness and safety of antidepressant medications for depressive episodes in these patients had not been well studied. At the time, antidepressants were commonly used as adjuncts to mood-stabilizing medication for bipolar disorder, despite limited evidence on their effectiveness and none having FDA-approved indications. STEP-BD was a double-blind, randomized, placebo-controlled study designed to evaluate the effectiveness of treatments for bipolar disorder and to provide results that would be generalizable to routine clinical practice. A total of 179 participants with bipolar depression were randomly assigned to receive up to 26 weeks of treatment with a mood stabilizer (lithium, valproate, or carbamazepine), plus an adjunctive antidepressant (paroxetine or bupropion) or a mood stabilizer plus a matching placebo. The primary outcome was durable recovery, defined as euthymia for at least 8 consecutive weeks. At the end of the study, there was no significant difference between the combination and monotherapy group in terms of meeting the primary endpoint (23.5% vs 27.3%; p=0.40). When looking at some of the secondary endpoints, the combination of a mood stabilizer plus antidepressant had numerically better results than mood stabilizer alone, though none reached statistical significance. The rate of any individual adverse event did not differ significantly between the 2 groups.
Adjunctive treatment with antidepressants does not appear to improve clinical outcomes in people with bipolar disorder taking a mood stabilizer