Antidepressant Trials Need Radical Methodology Reform

Journal of Psychiatry Reform Vol 9 #17. November 15, 2022


Alan Eppel MB, MRCPsych, FRCPC

The author has no conflicts of interest.

In this edition of the journal we have reprinted a Danish Cochrane reanalysis of a meta-analysis conducted by Cipriani et al [1]. The original meta-analysis was carried out over many years and was exhaustive in scope [2]. However the results of the analysis were questioned on the basis of methodology and potential bias [3].

The reanalysis by Munkholm et al illustrates the complexity of current methodologies and the difficulty in appraising the validity of study findings. The authors assessed multiple variables including trial duration, selective outcome reporting, relevance of clinical outcome measures, clinical versus statistical significance of results, and certainty of evidence.

The authors concluded that the Cipriani study should not inform clinical practice. They stressed the need for “radical change in the way antidepressant trials are being conducted reported and interpreted”.

In order to get more relevant and reliable outcomes the authors recommend  “large-scale, industry-independent and better blinded, long-term trials of drug naïve participants, with patient-relevant outcomes rather than ranking scales”.

These conclusions have widespread importance in psychiatry and should be kept in mind when appraising the psychiatric research literature.




1. Munkholm K, Paludan-Müller AS, Boesen K. Considering the methodological

limitations in the evidence base of antidepressants for depression: a reanalysis

of a network meta-analysis. BMJ Open. 2019 Jun 27;9(6):e024886. doi:


2. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and

acceptability of 21 antidepressant drugs for the acute treatment

of adults with major depressive disorder: a systematic review and

network meta-analysis. Lancet 2018;391:1357–66.

3. Eppel A. Network meta-analysis of antidepressants: a bridge too far? Journal of Psychiatry Reform. 2019 Jan5; (1):

Network Meta-analysis of Antidepressants: A Bridge Too Far?



Print Friendly, PDF & Email