TY - JOUR
T1 - Improvements in irritability with sertraline versus placebo
T2 - Findings from the EMBARC study
AU - Jha, Manish K.
AU - Minhajuddin, Abu
AU - Chin Fatt, Cherise
AU - Trivedi, Madhukar H.
N1 - Funding Information:
The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study was supported by NIMH Grants U01MH092221 (PI: Trivedi) and U01MH092250 (PIs: McGrath, Parsey, and Weissman). This work was also funded in part by the Hersh Foundation (PI: Trivedi). The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services , nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data.
Funding Information:
The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study was supported by NIMH Grants U01MH092221 (PI: Trivedi) and U01MH092250 (PIs: McGrath, Parsey, and Weissman). This work was also funded in part by the Hersh Foundation (PI: Trivedi). The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data.
Funding Information:
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.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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
AB - 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
KW - Antidepressant
KW - Irritability
KW - Major depressive disorder
KW - Placebo
KW - Randomized controlled trial
KW - SSRI
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U2 - 10.1016/j.jad.2020.06.021
DO - 10.1016/j.jad.2020.06.021
M3 - Article
C2 - 32658822
AN - SCOPUS:85087296358
VL - 275
SP - 44
EP - 47
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
ER -