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

  • Manish K. Jha (a1) (a2), Maurizio Fava (a3), Abu Minhajuddin (a2), Cherise Chin Fatt (a2), David Mischoulon (a3), Nausheen Wakhlu (a2), Joseph M. Trombello (a2), Cristina Cusin (a3) and Madhukar H. Trivedi (a2)...



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).


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.


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.


The presence of anger attacks in outpatients with major depressive disorder may identify a sub-group of patients with persistently elevated irritability.


Corresponding author

Author for correspondence: Madhukar H. Trivedi, E-mail:


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

  • Manish K. Jha (a1) (a2), Maurizio Fava (a3), Abu Minhajuddin (a2), Cherise Chin Fatt (a2), David Mischoulon (a3), Nausheen Wakhlu (a2), Joseph M. Trombello (a2), Cristina Cusin (a3) and Madhukar H. Trivedi (a2)...


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