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

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.