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Are Add-On Antidepressants Ineffective for Bipolar Depression?

Antidepressants and placebo showed similar results when given adjunctively with mood stabilizers.

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.

Comment: A recent meta-analysis suggested efficacy for antidepressants in bipolar depression (Am J Psychiatry 2004; 161:1537); however, only 1 of the 12 included studies was placebo-controlled, involved mood-stabilizer treatment, and had positive findings. The current study might also have had different results because participants had comorbid illnesses, remission had to last 8 weeks, and patients with recent mania or with histories of antidepressant-induced mania may have been discouraged from enrolling.

Over time, depressed bipolar patients may do as well with mood stabilizers alone as with add-on antidepressants. Still, clinicians concerned about suicidality will continue to prescribe antidepressants for seriously depressed bipolar patients. Thus, the finding that adjunctive antidepressants did not increase risk for mania is reassuring. More study of antidepressant properties and mood-stabilizer efficacy is warranted.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry March 28, 2007

Citation(s):

Sachs GS et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007 Mar 28; [Epub ahead of print]. (http://content.nejm.org/cgi/content/short/NEJMoa064135)