To examine whether the conclusion of a recent systematic review and network meta-analysis (Cipriani et al.) that antidepressants are more effective than placebo for adult depression was supported by the evidence.
Several methodologic limitations in the evidence base for antidepressants were either not recognized or underestimated in the systematic review by Cipriani et al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in studies with a “placebo run-in” study design than in studies without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published studies than in unpublished studies (p<0.0001). Outcome data reported by Cipriani et al. differed from clinical trial reports in 12 (63%) of 19 studies. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of evidence, and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton Depression Rating Scale (range 0-52 points) was 1.97 points (95% CI 1.74 to 2.21).
The evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more effective than placebo.