Primary prevention of depression: An umbrella review of controlled interventions

Gonzalo Salazar de Pablo, Marco Solmi, Julio Vaquerizo-Serrano, Joaquim Radua, Anastassia Passina, Pierluca Morsillo, Christoph U. Correll, Stefan Borgwardt, Silvana Galderisi, Andreas Bechdolf, Andrea Pfennig, Michael Bauer, Lars Vedel Kessing, Therese van Amelsvoort, Dorien H. Nieman, Katharina Domschke, Marie Odile Krebs, Michael Sand, Eduard Vieta, Philip McGuireCelso Arango, Jae Il Shin, Paolo Fusar-Poli

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)


Background: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined. Methods: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations. Results: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility. Limitations: Intervention heterogeneity and lack of long-term efficacy evaluation. Conclusions: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period.

Original languageEnglish
Pages (from-to)957-970
Number of pages14
JournalJournal of affective disorders
Publication statusPublished - 2021 Nov 1

Bibliographical note

Funding Information:
GSP has received honoraria from Janssen Cilag. CUC has been a consultant and/or advisor to or has received honoraria from Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka. He served on a Data Safety Monitoring Board for Boehringer-Ingelheim, Lundbeck, Rovi, Supernus, and Teva. He received royalties from UpToDate and grant support from Janssen and Takeda. He is also a shareholder of LB Pharma. SB acknowledges support from the University of Basel, the European Union's Seventh Framework Programme, the Swiss National Science Foundation and the ERA-NET. SB has received educational funds from Sunovion, Otsuka, Recordati, Servier, Janssen and Lundbeck. SG has been consultant or has received honoraria or grants from Millennium Pharmaceuticals; Innova Pharma – Recordati Group; Janssen Pharmaceutica, Sunovion Pharmarmaceuticals¸ Janssen-Cilag Polska; Gedeon Richter; Pierre Fabre; Otsuka and Angelini. AB received unrestricted scientific grants of the German Research Foundation (DFG), The German Ministry for Education and Research (BMBF) and Janssen; further speaker and travel grants were provided from Otsuka, Lundbeck and Janssen. LVK has within recent three years been a consultant for Lundbeck and Teva. EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbvie, Aimentia, Angelini, Celon, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Janssen, Lundbeck, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. PFP has been a consultant to and received research funds from Lundbeck and received honoraria from Menarini.

Funding Information:
The study was supported by the European College of Neuropsychopharmacology Network Taskforce. GSP is supported by the Alicia Koplowitz Foundation. CA is supported by the Spanish Ministry of Science, Innovation, and Universties, Instituto de Salud Carlos III, European Regional Development Fund ‘A way of making Europe,’ Centro de Investigacion Biomedica en Red Salud Mental, Madrid Regional Government; and Fundación Mutua Madrileña

Publisher Copyright:
© 2021 The Authors

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health


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