Abstract
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 language | English (US) |
---|---|
Pages (from-to) | 1355-1363 |
Number of pages | 9 |
Journal | Psychological Medicine |
Volume | 51 |
Issue number | 8 |
DOIs | |
State | Published - Jun 2021 |
Keywords
- Anger attacks
- antidepressant treatment
- anxiety
- irritability
- major depressive disorder
ASJC Scopus subject areas
- Applied Psychology
- Psychiatry and Mental health
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In: Psychological Medicine, Vol. 51, No. 8, 06.2021, p. 1355-1363.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Anger attacks are associated with persistently elevated irritability in MDD
T2 - Findings from the EMBARC study
AU - Jha, Manish K.
AU - Fava, Maurizio
AU - Minhajuddin, Abu
AU - Chin Fatt, Cherise
AU - Mischoulon, David
AU - Wakhlu, Nausheen
AU - Trombello, Joseph M.
AU - Cusin, Cristina
AU - Trivedi, Madhukar H.
N1 - Funding Information: Dr Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and PeerPoint Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book ‘Natural Medications for Psychiatric Disorders: Considering the Alternatives.’ Dr Cusin has received research support from Shenox. She has received consulting honoraria from Janssen, Takeda, Boehringer, Lundbeck, and Alkermes. She has received royalties from Springer for published book ‘The Massachusetts General Hospital Guide to Depression.’ Dr Trombello owns stock in Merck Pharmaceuticals and within the past 36 months owned stock in Gilead Sciences, both unrelated to the current project. 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. Funding Information: Financial support. The EMBARC study was supported by NIMH grants U01MH092221 (to Dr Trivedi) and U01MH092250 (to Drs. McGrath, Parsey, and Weissman). This work was also funded in part by the Hersh Foundation (Dr Trivedi, principal investigator). The CO-MED trial was funded by NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (principal investigators, A.J. Rush and M.H. Trivedi). Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for CO-MED trial at no cost. 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. The authors thank the clinical staff at each clinical site for their assistance with these projects; all of the study participants; Eric Nestler, M.D., Ph.D., and Carol A. Tamminga, M.D., for administrative support. Funding Information: Conflict of interest. Ms. Wakhlu and Drs. Minhajuddin and Chin Fatt have no conflicts to report. Dr Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development. Dr Fava has received research support from Abbot Laboratories Alkermes, American Cyanamid, Aspect Medical Systems, AstraZeneca, Avanir Pharmaceuticals, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clintara, Cerecor, Covance, Covidien, Eli Lilly, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Harvard Clinical Research Institute, Hoffman-LaRoche, Icon Clinical Research, i3 Innovus/Ingenix, Janssen R&D, Jed Foundation, Johnson & Johnson Pharmaceutical Research and Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Lundbeck, MedAvante, Methylation Sciences, NARSAD, National Center for Complementary and Alternative Medicine, Neuralstem, NIDA, NIMH, Novartis, Organon Pharmaceuticals, Pamlab, Pfizer, Pharmacia-Upjohn, Pharmaceutical Research Associates, Pharmavite, PharmoRx Therapeutics, Photothera, Reckitt Benckiser, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials Solutions), Sanofi-Aventis US, Shire, Solvay Pharmaceuticals, Stanley Medical Research Institute, Synthelabo, Tal Medical, and Wyeth-Ayerst Laboratories; he has served as adviser or consultant to Abbott Laboratories, Acadia, Affectis Pharmaceuticals, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Avanir Pharmaceuticals, AXSOME Therapeutics, Bayer, Best Practice Project Management, Biogen, BioMarin Pharmaceuticals, Biovail Corporation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Cerecor, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dainippon Sumitomo Pharma, Dov Pharmaceuticals, Edgemont Pharmaceuticals, Eisai, Eli Lilly, EnVivo Pharmaceuticals, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, Forum Pharmaceuticals, GenOmind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Intracellular, Janssen Pharmaceutica, Jazz Pharmaceuticals, Johnson & Johnson Pharmaceutical Research and Development, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Nestle Health Sciences, Neuralstem, Neuronetics, NextWave Pharmaceuticals, Novartis, Nutrition 21, Orexigen Therapeutics, Organon Pharmaceuticals, Osmotica, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, RCT Logic (Formerly Clinical Trials Solutions), Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, Sanofi-Aventis US, Sepracor, Servier Laboratories, Schering-Plough, Solvay Pharmaceuticals, Somaxon Pharmaceuticals, Somerset Pharmaceuticals, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Synthelabo, Taisho Pharmaceutical, Takeda Pharmaceutical Company, Tal Medical, Tetragenex Pharmaceuticals, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals, and VistaGen; he has received speaking or publishing fees from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, CME Institute/Physicians Postgraduate Press, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, MGH Psychiatry Academy/ Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis, Organon Pharmaceuticals, Pfizer, PharmaStar, United BioSource, and Wyeth-Ayerst Laboratories; he has equity holdings in Compellis and PsyBrain; he has a patent for Sequential Parallel Comparison Design, which are licensed by Massachusetts General Hospital to Pharmaceutical Product Development, and a patent application for a combination of ketamine plus scopolamine in MDD, licensed by Massachusetts General Hospital to Biohaven; and he receives royalties for the MGH Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, the Symptoms of Depression Questionnaire, and SAFER, and from Lippincott, Williams & Wilkins, Wolkers Kluwer, and World Scientific Publishing. Publisher Copyright: Copyright © The Author(s) 2020. Published by Cambridge University Press.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Anger attacks
KW - antidepressant treatment
KW - anxiety
KW - irritability
KW - major depressive disorder
UR - http://www.scopus.com/inward/record.url?scp=85082069704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082069704&partnerID=8YFLogxK
U2 - 10.1017/S0033291720000112
DO - 10.1017/S0033291720000112
M3 - Article
C2 - 32138798
AN - SCOPUS:85082069704
SN - 0033-2917
VL - 51
SP - 1355
EP - 1363
JO - Psychological Medicine
JF - Psychological Medicine
IS - 8
ER -