Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: A mega-analysis of citalopram and paroxetine in adult depression

Abstract

It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n = 15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects. (PsycINFO Database Record (c) 2020 APA, all rights reserved)

Accession Number: 2019-32509-005. PMID: 29155804 Partial author list: First Author & Affiliation: Hieronymus, F.; Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,  ORCID: 0000-0003-0930-6068. Release Date: 20200319. Publication Type: Journal (0100), Peer Reviewed Journal (0110). Format Covered: Electronic. Document Type: Journal Article. Language: English. Major Descriptor: Citalopram; Major Depression; Paroxetine; Rating Scales; Serotonin Reuptake Inhibitors. Minor Descriptor: Antidepressant Drugs; Placebo; Patient Selection. Classification: Affective Disorders (3211); Clinical Psychopharmacology (3340). Population: Human (10). Age Group: Adulthood (18 yrs & older) (300). Methodology: Empirical Study; Quantitative Study. Supplemental Data: Tables and Figures Internet. References Available: Y. Page Count: 6. Issue Publication Date: Aug, 2018. Publication History: First Posted Date: Jul 25, 2017; Accepted Date: May 30, 2017; Revised Date: May 2, 2017; First Submitted Date: Mar 15, 2017. Copyright Statement: This work is licensed under a Creative Commons Attribution- NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. The Author(s). 2018.