Improvements in irritability with sertraline versus placebo: Findings from the EMBARC study

Abstract

Background: This report seeks to evaluate improvements in symptoms of irritability with sertraline (a selective serotonin reuptake inhibitor antidepressant) versus placebo.

Methods: Participants of Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study who were randomized to 8 weeks of treatment with either sertraline or placebo and completed 5-item irritability domain of Concise Associated Symptom Tracking scale (CAST-IRR) at baseline were included (n = 292). Repeated measures mixed model analysis with CAST-IRR as the outcome variable and treatment arm-by-time interaction as the independent variable of interest evaluated whether changes in irritability with treatment differed between sertraline and placebo arms. A separate analysis controlled for levels of overall depression severity (17-item Hamilton Depression Rating Scale). Covariates included age, sex, race, ethnicity, and site.

Results: There was a significant treatment arm-by-time interaction (F = 6.96, df = 6, 1418, p <0.0001) suggesting that changes in irritability with sertraline differed from placebo. The magnitude of reduction in irritability from baseline to week-8 was greater with sertraline than with placebo (Cohen's d effect size = 0.56). After controlling for levels of overall depression severity at each visit, reduction in irritability with time continued to be significant with sertraline but not with placebo.

Limitations: Secondary analysis, limited generalizability, lack of non-serotonergic antidepressants.

Discussion: There is greater improvement in irritability with sertraline than with placebo. Improvement in irritability with sertraline was independent of its effects on overall depression severity. CLINICALTRIALS.

Gov identifier: NCT01407094.

Keywords: Antidepressant; Irritability; Major depressive disorder; Placebo; Randomized controlled trial; SSRI.

Conflict of interest statement

Declartion of Competing Interest Drs. Minhajuddin and Chin Fatt have no conflicts to report. Dr. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. Dr. Trivedi has served as an adviser or consultant for Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories; he has received grants or research support from the Agency for Healthcare Research and Quality, Cyberonics, NARSAD, NIDA, and NIMH.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Figure 1.

Changes in irritability during Stage 1 of EMBARC study Least square (LS) means obtained from mixed model analyses (error bars present standard errors) with 5-item irritability domain of Concise Associated Symptom Tracking (CAST-IRR) as the dependent variable in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study. Participants were randomized in 1:1 fashion to sertraline (n=143) or placebo (n=149) for 8 weeks during Stage 1 of EMBARC. * p