Anger attacks are associated with persistently elevated irritability in MDD: Findings from the EMBARC study

Manish K. Jha, Maurizio Fava, Abu Minhajuddin, Cherise Chin Fatt, David Mischoulon, Nausheen Wakhlu, Joseph M. Trombello, Cristina Cusin, Madhukar H. Trivedi

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background This report tests the association of self-reported symptoms of irritability with overt behavior of anger attacks (uncharacteristic sudden bouts of anger that are disproportionate to situation and associated with autonomic activation). Methods Participants of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study who completed Massachusetts General Hospital Anger Attacks questionnaire were included (n = 293). At each visit, the 17-item Hamilton Depression Rating Scale and the 16-item Concise Associated Symptom Tracking scale were used to measure depression, anxiety, and irritability. In those with anger attacks present v.Those without anger attacks, separate t tests and mixed model analyses compared afore-mentioned symptoms at baseline and changes with treatment respectively. As anger attacks may occur without aggressive behaviors, analyses were repeated based only on the presence of aggressive behaviors. Results At baseline, those with anger attacks (n = 109) v.Those without anger attacks (n = 184) had similar levels of depression but higher levels of irritability [effect size (d) = 0.80] and anxiety (d = 0.32). With acute-phase treatment, participants with anger attacks experienced a greater reduction in irritability (p < 0.001) but not in depression (p = 0.813) or anxiety (p = 0.771) as compared to those without anger attacks. Yet, irritability levels at week-8 were higher in those with anger attacks (d = 0.32) than those without anger attacks. Similar results were found in participants with aggressive behaviors. Conclusions The presence of anger attacks in outpatients with major depressive disorder may identify a sub-group of patients with persistently elevated irritability.

Original languageEnglish (US)
Pages (from-to)1355-1363
Number of pages9
JournalPsychological Medicine
Issue number8
StatePublished - Jun 2021


  • Anger attacks
  • antidepressant treatment
  • anxiety
  • irritability
  • major depressive disorder

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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