Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-26T07:34:45.453Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  06 March 2020

Manish K. Jha ,
Maurizio Fava ,
Abu Minhajuddin ,
Cherise Chin Fatt ,
David Mischoulon ,
Nausheen Wakhlu ,
Joseph M. Trombello ,
Cristina Cusin  and
Madhukar H. Trivedi Open the ORCID record for Madhukar H. Trivedi [Opens in a new window]
Manish K. Jha
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
Maurizio Fava
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Abu Minhajuddin
Affiliation:
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
Cherise Chin Fatt
Affiliation:
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
David Mischoulon
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Nausheen Wakhlu
Affiliation:
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
Joseph M. Trombello
Affiliation:
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
Cristina Cusin
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
Madhukar H. Trivedi*
Affiliation:
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA
*
Author for correspondence: Madhukar H. Trivedi, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Anger attacksantidepressant treatmentanxietyirritabilitymajor depressive disorder
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 8 , June 2021 , pp. 1355 - 1363
Check for updates
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Association, A. P (2013). Diagnostic and statistical manual of mental disorders (DSM-5 ®). Arlington, VA: American Psychiatric Pub.Google Scholar
Brotman, M. A., Kircanski, K., Stringaris, A., Pine, D. S., & Leibenluft, E. (2017). Irritability in youths: A translational model. American Journal of Psychiatry, 174(6), 520–532. doi:10.1176/appi.ajp.2016.16070839CrossRefGoogle ScholarPubMed
Chandler, G. M., Iosifescu, D. V., Pollack, M. H., Targum, S. D., & Fava, M. (2010). RESEARCH: Validation of the Massachusetts General Hospital Antidepressant Treatment History Questionnaire (ATRQ). CNS Neuroscience & Therapeutics, 16(5), 322–325. doi: 10.1111/j.1755-5949.2009.00102.xCrossRefGoogle Scholar
Cohen, J. (2013). Statistical power analysis for the behavioral sciences, (Vol 2). Routledge, p. 40.CrossRefGoogle Scholar
Dougherty, D. D., Bonab, A. A., Ottowitz, W. E., Livni, E., Alpert, N. M., Rauch, S. L., … Fischman, A. J. (2006). Decreased striatal D1 binding as measured using PET and [11C]SCH 23390 in patients with major depression with anger attacks. Depression and Anxiety, 23(3), 175–177. doi:10.1002/da.20168CrossRefGoogle Scholar
Fava, M. (1998). Depression with anger attacks. Journal of Clinical Psychiatry, 59(Suppl 18), 18–22.Google ScholarPubMed
Fava, M., Abraham, M., Pava, J., Shuster, J., & Rosenbaum, J. (1996). Cardiovascular risk factors in depression. The role of anxiety and anger. Psychosomatics, 37(1), 31–37. doi:10.1016/s0033-3182(96)71595-5CrossRefGoogle ScholarPubMed
Fava, M., Anderson, K., & Rosenbaum, J. F. (1990). “Anger attacks”: Possible variants of panic and major depressive disorders. American Journal of Psychiatry, 147(7), 867–870. doi: 10.1176/ajp.147.7.867Google ScholarPubMed
Fava, M., Hwang, I., Rush, A. J., Sampson, N., Walters, E. E., & Kessler, R. C. (2010). The importance of irritability as a symptom of major depressive disorder: Results from the National Comorbidity Survey Replication. Molecular Psychiatry, 15(8), 856.CrossRefGoogle ScholarPubMed
Fava, M., Rosenbaum, J. F., McCarthy, M., Pava, J., Steingard, R., & Bless, E. (1991). Anger attacks in depressed outpatients and their response to fluoxetine. Psychopharmacology Bulletin, 27(3), 275–279.Google ScholarPubMed
Fava, M., Rosenbaum, J. F., Pava, J. A., McCarthy, M. K., Steingard, R. J., & Bouffides, E. (1993). Anger attacks in unipolar depression, Part 1: Clinical correlates and response to fluoxetine treatment. American Journal of Psychiatry, 150(8), 1158–1163. doi: 10.1176/ajp.150.8.1158Google ScholarPubMed
Fava, M., Vuolo, R. D., Wright, E. C., Nierenberg, A. A., Alpert, J. E., & Rosenbaum, J. F. (2000). Fenfluramine challenge in unipolar depression with and without anger attacks. Psychiatry Research, 94(1), 9–18.CrossRefGoogle ScholarPubMed
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. (2002). Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. Biometrics Research Institute, New York State Psychiatric Institute.Google Scholar
Fitzgerald, P., & Dinan, T. G. (2008). Prolactin and dopamine: What is the connection? A review article. Journal of Psychopharmacology, 22(2 Suppl), 12–19. doi: 10.1177/0269216307087148CrossRefGoogle ScholarPubMed
Flanigan, M. E., Aleyasin, H., Li, L., Burnett, C. J., Chan, K. L., LeClair, K. B., … Russo, S. J. (2019). Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior. bioRxiv, 811265. doi:10.1101/811265.Google Scholar
Fraguas, R., Iosifescu, D. V., Bankier, B., Perlis, R., Clementi-Craven, N., Alpert, J., & Fava, M. (2007). Major depressive disorder with anger attacks and cardiovascular risk factors. International Journal of Psychiatry in Medicine, 37(1), 99–111. doi: 10.2190/y361-2w83-268h-5w7vCrossRefGoogle ScholarPubMed
Fraguas, R. Jr., Papakostas, G. I., Mischoulon, D., Bottiglieri, T., Alpert, J., & Fava, M. (2006). Anger attacks in major depressive disorder and serum levels of homocysteine. Biological Psychiatry, 60(3), 270–274. doi:10.1016/j.biopsych.2005.08.026CrossRefGoogle ScholarPubMed
Gold, P. W., & Kadriu, B. (2019). A major role for the lateral habenula in depressive illness: Physiologic and molecular mechanisms. Frontiers in Psychiatry, 10, 320. doi: 10.3389/fpsyt.2019.00320CrossRefGoogle Scholar
Golden, S. A., Heshmati, M., Flanigan, M., Christoffel, D. J., Guise, K., Pfau, M. L., … Russo, S. J. (2016). Basal forebrain projections to the lateral habenula modulate aggression reward. Nature, 534(7609), 688–692. doi:10.1038/nature18601CrossRefGoogle ScholarPubMed
Iosifescu, D. V., Renshaw, P. F., Dougherty, D. D., Lyoo, I. K., Lee, H. K., Fraguas, R., … Fava, M. (2007). Major depressive disorder with anger attacks and subcortical MRI white matter hyperintensities. Journal of Nervous and Mental Disease, 195(2), 175–178. doi:10.1097/01.nmd.0000253820.69362.87CrossRefGoogle ScholarPubMed
Jha, M. K., Grannemann, B. D., Trombello, J. M., Clark, E. W., Eidelman, S. L., Lawson, T., … Trivedi, M. H. (2019). A structured approach to detecting and treating depression in primary care: VitalSign6 project. Annals of Family Medicine, 17(4), 326–335. doi:10.1370/afm.2418CrossRefGoogle ScholarPubMed
Jha, M. K., Minhajuddin, A., South, C., Rush, A. J., & Trivedi, M. H. (2018). Worsening anxiety, irritability, insomnia, or panic predicts poorer antidepressant treatment outcomes: Clinical utility and validation of the Concise Associated Symptom Tracking (CAST) Scale. International Journal of Neuropsychopharmacology, 21(4), 325–332. doi: 10.1093/ijnp/pyx097.CrossRefGoogle ScholarPubMed
Jha, M. K., Minhajuddin, A., South, C., Rush, A. J., & Trivedi, M. H. (2019). Irritability and its clinical utility in major depressive disorder: Prediction of individual-level acute-phase outcomes using early changes in irritability and depression severity. American Journal of Psychiatry, 176(5), 358–366. doi: 10.1176/appi.ajp.2018.18030355.CrossRefGoogle ScholarPubMed
Judd, L. L., Schettler, P. J., Coryell, W., Akiskal, H. S., & Fiedorowicz, J. G. (2013). Overt irritability/anger in unipolar major depressive episodes: Past and current characteristics and implications for long-term course. JAMA Psychiatry, 70(11), 1171–1180. doi: 10.1001/jamapsychiatry.2013.1957.CrossRefGoogle ScholarPubMed
Kircanski, K., White, L. K., Tseng, W. L., Wiggins, J. L., Frank, H. R., Sequeira, S., … Brotman, M. A. (2018). A latent variable approach to differentiating neural mechanisms of irritability and anxiety in youth. JAMA Psychiatry, 75(6), 631–639. doi:10.1001/jamapsychiatry.2018.0468CrossRefGoogle ScholarPubMed
Kroenke, K., Spitzer, R. L., & Williams, J. B. (2001). The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine, 16(9), 606–613. doi: 10.1046/j.1525-1497.2001.016009606.xCrossRefGoogle ScholarPubMed
Minhajuddin, A., Jha, M. K., Chin Fatt, C., & Trivedi, M. H. (2020). Psychometric Properties of Concise Associated Symptom Tracking (CAST) Scale and Validation of its Clinical Utility in Patients with Major Depressive Disorder: Findings from the EMBARC Study. Psychiatric Research and Clinical Practice. In Press.CrossRefGoogle Scholar
Orri, M., Perret, L. C., Turecki, G., & Geoffroy, M. C. (2018). Association between irritability and suicide-related outcomes across the life-course. Systematic review of both community and clinical studies. Journal of Affective Disorders, 239, 220–233. doi: 10.1016/j.jad.2018.07.010CrossRefGoogle ScholarPubMed
Painuly, N. P., Grover, S., Gupta, N., & Mattoo, S. K. (2011). Prevalence of anger attacks in depressive and anxiety disorders: Implications for their construct? Psychiatry and Clinical Neuroscience, 65(2), 165–174. doi: 10.1111/j.1440-1819.2010.02177.xCrossRefGoogle ScholarPubMed
Painuly, N., Sharan, P., & Mattoo, S. K. (2007). Antecedents, concomitants and consequences of anger attacks in depression. Psychiatry Research, 153(1), 39–45. doi: 10.1016/j.psychres.2006.03.001CrossRefGoogle ScholarPubMed
Pine, D. S. (2019). Heterogeneity in major depressive disorder: Lessons from developmental research on irritability. American Journal of Psychiatry, 176(5), 331–332. doi: 10.1176/appi.ajp.2019.19020214CrossRefGoogle ScholarPubMed
Pizzagalli, D. A., Evins, A. E., Schetter, E. C., Frank, M. J., Pajtas, P. E., Santesso, D. L., & Culhane, M. (2008). Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness. Psychopharmacology (Berl), 196(2), 221–232. doi: 10.1007/s00213-007-0957-yCrossRefGoogle ScholarPubMed
Rosenbaum, J. F., Fava, M., Pava, J. A., McCarthy, M. K., Steingard, R. J., & Bouffides, E. (1993). Anger attacks in unipolar depression, Part 2: Neuroendocrine correlates and changes following fluoxetine treatment. American Journal of Psychiatry, 150(8), 1164–1168. doi: 10.1176/ajp.150.8.1164Google ScholarPubMed
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., … Keller, M. B. (2003). The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression. Biological Psychiatry, 54(5), 573–583. doi:10.1016/s0006-3223(02)01866-8.CrossRefGoogle ScholarPubMed
Stoddard, J., Tseng, W. L., Kim, P., Chen, G., Yi, J., Donahue, L., … Leibenluft, E. (2017). Association of irritability and anxiety with the neural mechanisms of implicit face emotion processing in youths with psychopathology. JAMA Psychiatry, 74(1), 95–103. doi:10.1001/jamapsychiatry.2016.3282.CrossRefGoogle ScholarPubMed
Trivedi, M. H., Jha, M. K., Kahalnik, F., Pipes, R., Levinson, S., Lawson, T., … Greer, T. L. (2019). Vitalsign(6): A primary care first (PCP-First) model for universal screening and measurement-based care for depression. Pharmaceuticals (Basel), 12(2), 1–18. doi:10.3390/ph12020071CrossRefGoogle ScholarPubMed
Trivedi, M. H., McGrath, P. J., Fava, M., Parsey, R. V., Kurian, B. T., Phillips, M. L., … Weissman, M. M. (2016). Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design. Journal of Psychiatric Research, 78, 11–23. doi:10.1016/j.jpsychires.2016.03.001CrossRefGoogle ScholarPubMed
Trivedi, M. H., South, C., Jha, M. K., Rush, A. J., Cao, J., Kurian, B., … Fava, M. (2018). A novel strategy to identify placebo responders: Prediction index of clinical and biological markers in the EMBARC trial. Psychotherapy Psychosomatics, 87(5), 285–295. doi:10.1159/000491093CrossRefGoogle ScholarPubMed
Trivedi, M. H., Wisniewski, S. R., Morris, D. W., Fava, M., Kurian, B. T., Gollan, J. K., … Rush, A. J. (2011). Concise Associated Symptoms Tracking scale: A brief self-report and clinician rating of symptoms associated with suicidality. Journal of Clinical Psychiatry, 72(6), 765–774. doi:10.4088/JCP.11m06840CrossRefGoogle ScholarPubMed
Van Praag, H. M. (2001). Anxiety/aggression – driven depression: A paradigm of functionalization and verticalization of psychiatric diagnosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25(4), 893–924. doi:https://doi.org/10.1016/S0278-5846(01)00151-8CrossRefGoogle ScholarPubMed
Vittengl, J. R., Clark, L. A., Kraft, D., & Jarrett, R. B. (2005). Multiple measures, methods, and moments: A factor-analytic investigation of change in depressive symptoms during acute-phase cognitive therapy for depression. Psychological Medicine, 35(5), 693–704.10.1017/S0033291704004143CrossRefGoogle ScholarPubMed
Williams, J. B. (1988). A structured interview guide for the Hamilton Depression Rating Scale. Archives of General Psychiatry, 45(8), 742–747.10.1001/archpsyc.1988.01800320058007CrossRefGoogle ScholarPubMed
Zimmerman, M., Balling, C., Chelminski, I., & Dalrymple, K. (2019). Have treatment studies of depression become even less generalizable? Applying the inclusion and exclusion criteria in placebo-controlled antidepressant efficacy trials published over 20 years to a clinical sample. Psychotherapy Psychosomatics, 88(3), 165–170. doi: 10.1159/000499917CrossRefGoogle ScholarPubMed
Supplementary material: File

Jha et al. supplementary material

Figure S1 and Tables S1-S2

Download Jha et al. supplementary material(File)
File 338.2 KB