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Exploring the efficacy of psychotherapies for depression: a multiverse meta-analysis
  1. Constantin Yves Plessen1,2,
  2. Eirini Karyotaki2,3,4,
  3. Clara Miguel2,3,
  4. Marketa Ciharova2,3,
  5. Pim Cuijpers2,3,4
  1. 1 Department of Psychosomatic Medicine, Charite University Hospital Berlin, Berlin, Germany
  2. 2 Department of Clinical, Neuro-, and Developmental Psychology, Vrije Universiteit Amsterdam Faculty of Behavioural and Movement Sciences, Amsterdam, The Netherlands
  3. 3 Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  4. 4 WHO Collaborating Center for Research and Dissemination of Psychological Interventions, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Constantin Yves Plessen, Charite University Hospital Berlin, Berlin, Germany; constantin-yves.plessen{at}


Background Hundreds of randomised controlled trials and dozens of meta-analyses have examined psychotherapies for depression—yet not all points in the same direction. Are these discrepancies a result of specific meta-analytical decisions or do most analytical strategies reaching the same conclusion?

Objective We aim to solve these discrepancies by conducting a multiverse meta-analysis containing all possible meta-analyses, using all statistical methods.

Study selection and analysis We searched four bibliographical databases (PubMed, EMBASE, PsycINFO and Cochrane Register of Controlled Trials), including studies published until 1 January 2022. We included all randomised controlled trials comparing psychotherapies with control conditions without restricting the type of psychotherapy, target group, intervention format, control condition and diagnosis. We defined all possible meta-analyses emerging from combinations of these inclusion criteria and estimated the resulting pooled effect sizes with fixed-effect, random-effects, 3-level, robust variance estimation, p-uniform and PET-PEESE (precision-effect test and precision-effect estimate with SE) meta-analysis models. This study was preregistered (

Findings A total of 21 563 records were screened, and 3584 full texts were retrieved; 415 studies met our inclusion criteria containing 1206 effect sizes and 71 454 participants. Based on all possible combinations between inclusion criteria and meta-analytical methods, we calculated 4281 meta-analyses. The average summary effect size for these meta-analyses was Hedges’ g mean=0.56, a medium effect size, and ranged from g=−0.66 to 2.51. In total, 90% of these meta-analyses reached a clinically relevant magnitude.

Conclusions and Clinical Implications The multiverse meta-analysis revealed the overall robustness of the effectiveness of psychotherapies for depression. Notably, meta-analyses that included studies with a high risk of bias, compared the intervention with wait-list control groups, and not correcting for publication bias produced larger effect sizes.

  • Depression & mood disorders

Data availability statement

Data are available in a public, open access repository. The R code and data to reproduce all analyses can be found at the Open Science Framework.

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Data availability statement

Data are available in a public, open access repository. The R code and data to reproduce all analyses can be found at the Open Science Framework.

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  • Contributors CYP conceived of the presented idea and is responsible for the overall content as guarantor. PC, CM, MC and EK prepared the data curation. CYP analysed the data and wrote the initial draft. The draft was reviewed and edited by CM, MC, PC and EK. PC and EK supervised the findings of this work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.