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Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks


S. Nassir Ghaemi, MD, Tufts University School of Medicine, 800 Washington Street, Boston, MA 02111, USA.


Objective:  Long-term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta-analysis of available research.

Method:  We reviewed randomized controlled trials for BPD involving ≥6 months of treatment with AD ± mood stabilizer (MS) vs. placebo ± MS, using meta-analyses to compare reported risks of new depression vs. mania.

Results:  In seven trials (350 BPD patients) involving 12 contrasts, long-term treatments that included ADs yielded 27% lower risk of new depression vs. MS-only or no treatment [pooled relative risk, RR = 0.73; 95% CI 0.55–0.97; number-needed-to-treat (NNT) = 11], but 72% greater risk for new mania [RR = 1.72; 95% CI 1.23–2.41; number-needed-to-harm (NNH) = 7]. Compared with giving an MS-alone, adding an AD yielded neither major protection from depression (RR = 0.84; 95% CI 0.56–1.27; NNT = 16) nor substantial increase in risk of mania (RR = 1.37; 95% CI 0.81–2.33; NNH = 16).

Conclusion:  Long-term adjunctive AD treatment was not superior to MS-alone in BPD, further encouraging reliance on MSs as the cornerstone of prophylaxis.

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