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

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Abstract
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.