During the last decade, several meta-analytic studies employing different methodological
approaches have had inconsistent conclusions regarding antidepressant efficacy. Herein, we aim to
comment on methodological aspects that may have contributed to disparate findings. We initially discuss
methodological inconsistencies and limitations related to the conduct of individual antidepressant
randomized controlled trials (RCTs), including differences in allocated samples, limitations of
psychometric scales, possible explanations for the heightened placebo response rates in antidepressant RCTs across the
past two decades as well as the reporting of conflicts of interest. In the second part of this article, we briefly describe the
various meta-analyses techniques (e.g., simple random effects meta-analysis and network meta-analysis) and the application
of these methods to synthesize evidence related to antidepressant efficacy. Recently published antidepressant metaanalyses
often provide discrepant results and similar results often lead to different interpretations. Finally, we propose
strategies to improve methodology considering real-world clinical scenarios.
Keywords: Antidepressants, conflicts of interest, depression, meta-analysis, network meta-analysis, placebo, pooled analysis,
randomized controlled trial, rating scales.
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