Year: 2019
Type: article
Abstract: Importance: Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. Objective: To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes. Data Sources: PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019. Evidence Review: Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. Results: Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication. Conclusions and Relevance: This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.
Source: JAMA Psychiatry
Institutions: Linköping University, University of Ioannina, University of Padua, King's College London, National Health Service, South London and Maudsley NHS Foundation Trust, University of Pavia, National Institute for Health and Care Research, University of Greenwich, The University of Melbourne, University of Manchester, Western Sydney University, University of Naples Federico II, Centre for Addiction and Mental Health, University of Toronto, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Bethlem Royal Hospital, Yonsei University, Yonsei University Health System, Feinstein Institute for Medical Research, Hofstra University, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Zucker Hillside Hospital, Charité - Universitätsmedizin Berlin, Imperial College London
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Bristol-Myers Squibb, Pfizer, Teva Pharmaceutical Industries, South London and Maudsley NHS Foundation Trust, Sunovion, Indivior, Maudsley Charity, Northwell Health, Michael Smith Health Research BC, National Institute for Health and Care Research, Imperial College London, King's College London, Yonsei University, Gedeon Richter, University of Toronto, Linköpings Universitet, Ministerio de Ciencia e Innovación, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Servier, H. Lundbeck A/S, Berlin Institute of Health, Allergan, Department of Psychiatry, University of Toronto, Western Economic Diversification Canada, Yonsei University College of Medicine
OpenAlex ID: W2977696925