PMID:
BMJ Open. 2019 Jun 27 ;9(6):e024886. Epub 2019 Jun 27. PMID: 31248914
Abstract Title:
Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis.
Abstract:
OBJECTIVES: To investigate whether the conclusion of a recent systematic review and network meta-analysis (Cipriani) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DESIGN: Reanalysis of a systematic review, with meta-analyses.DATA SOURCES: 522 trials (116 477 participants) as reported in the systematic review by Ciprianiand clinical study reports for 19 of these trials.ANALYSIS: We used the Cochrane Handbook's risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.RESULTS: Several methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Cipriani. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a 'placebo run-in' study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p
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