Summary: | <h4>Objective</h4> <p>Previous studies reported effect sizes of antidepressants were larger in two- than in three- or more-armed (“multi-armed”) randomized trials, where the probability to be allocated to placebo is smaller. However, two-armed studies may have been subject to publication bias, did not take account of differences among antidepressants or covariance in multi-armed studies, or examine sponsorship bias.</p> <h4>Study design and setting</h4> <p>We searched published and unpublished randomized controlled trials that compared placebo with 21 antidepressants for the acute treatment of major depression in adults. We calculated the ratio of odds ratios (ROR) of drug response over placebo in two-armed versus multi-armed trials for each antidepressant, and then synthesized RORs across all the included antidepressants using the multi-variate meta-analysis. Random effects model was used throughout.</p> <h4>Results</h4> <p>Two hundred fifty eight trials (66 two-armed and 192 multi-armed trials; 80454 patients; 43.0% with unpublished data) were included in the present analyses. The pooled ROR for response of two-armed trials over multi-armed trials was 1.09 (95 %CI: 0.96 to 1.24). The ROR did not materially change between types of antidepressants, publication year or sponsorship.</p> <h4>Conclusion</h4> <p>The differences between two- versus multi-armed studies were much smaller than were suggested in previous studies and were not significant.</p>
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