Efficacy of selective serotonin reuptake inhibitors and adverse events: Meta-regression and mediation analysis of placebo-controlled trials
Efficacy of selective serotonin reuptake inhibitors and adverse events: Meta-regression and mediation analysis of placebo-controlled trials
Abstract
Background: It has been suggested that the efficacy of antidepressants has been overestimated in clinical trials owing to unblinding of drug treatments by adverse events. Aims: To investigate the association between adverse events and the efficacy of selective serotonin reuptake inhibitors (SSRIs). Method: The literature was searched to identify randomised, double-blind, placebo-controlled trials of SSRIs in the treatment of major depression. Efficacy outcomes were response to treatment and change in depressive symptoms. Reporting of adverse events was used as an indicator of tolerability. Random effects meta-analyses were used to calculate pooled estimates. Meta-regression analyses were performed to investigate the association between adverse events and efficacy. Potential mediation was investigated with the Baron & Kenny approach. Results: A total of 68 trials (n = 17 646) were included in the analyses. In meta-analysis SSRIs were superior to placebo in terms of efficacy (odds ratio, OR = 1.62, 95% CI 1.51–1.72). More patients allocated to SSRIs reported adverse events than did patients receiving placebo (OR = 1.73, 95% CI 1.58–1.89). Meta-regression analyses did not find an association between adverse events and efficacy (P = 0.439). There was no indication of adverse events mediating the effect of SSRI treatment. Conclusions: Our results do not support, but also do not unequivocally disprove, the hypothesis that adverse events lead to an overestimation of the effect of SSRIs over placebo. (PsycINFO Database Record (c) 2018 APA, all rights reserved)
Accession Number: 2016-45896-005. Other Journal Title: Journal of Mental Science; The Asylum Journal; The Asylum Journal of Mental Science. Partial author list: First Author & Affiliation: Barth, Michael; Institute for General Practice, Klinikum Rechts der Isar, Technische Universitat Munchen, Munchen, Germany, michael.barth@tum.de. Other Publishers: Cambridge University Press. Release Date: 20161103. Correction Date: 20180419. Publication Type: Journal (0100), Peer Reviewed Journal (0110). Format Covered: Electronic. Document Type: Journal Article. Language: English. Major Descriptor: Drug Therapy; Placebo; Serotonin Reuptake Inhibitors; Side Effects (Drug); Treatment Effectiveness Evaluation. Classification: Clinical Psychopharmacology (3340). Population: Human (10). Tests & Measures: Hamilton Rating Scale for Depression DOI: 10.1037/t04100-000. Methodology: Meta Analysis. References Available: Y. Page Count: 6. Issue Publication Date: Feb, 2016. Publication History: Accepted Date: Feb 26, 2015; First Submitted Date: Apr 22, 2014. Copyright Statement: The Royal College of Psychiatrists. 2016.
