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

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Ghaemi SN, Wingo AP, Filkowski MA, Baldessarini RJ. 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.

Keywords: antidepressants; bipolar disorder; depression; maintenance treatment; mania; meta-analysis; mood stabilizers; review of the literature

Document Type: Research Article


Affiliations: 1: Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA 2: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA

Publication date: November 1, 2008


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