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

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6 Scopus citations


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. identifier: NCT01407094

Original languageEnglish (US)
Pages (from-to)44-47
Number of pages4
JournalJournal of affective disorders
StatePublished - Oct 1 2020


  • Antidepressant
  • Irritability
  • Major depressive disorder
  • Placebo
  • Randomized controlled trial
  • SSRI

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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