TY - JOUR
T1 - Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder
AU - Jha, Manish K.
AU - Minhajuddin, Abu
AU - Chin Fatt, Cherise
AU - Kircanski, Katharina
AU - Stringaris, Argyris
AU - Leibenluft, Ellen
AU - Trivedi, Madhukar H.
N1 - Funding Information:
Combined Medications to Enhance Depression Outcomes (CO-MED) and Suicide Assessment and Methodology Study (SAMS) were funded by NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (PIs: Rush and MT). The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study was supported by NIMH grants U01MH092221 (PI: MT) and U01MH092250 (PIs: McGrath, Parsey, and Weissman). This work was also funded in part by the Hersh Foundation (PI: MT). Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for this CO-MED trial at no cost. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NIMH had no role in the drafting or review of the paper or in the collection or analysis of the data.
Funding Information:
AM, CCF, EL, and KK have no conflicts to report. MKJ has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. AS receives royalties from Oxford and Cambridge University Press. MT 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, Jans-sen 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.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
PY - 2020/12
Y1 - 2020/12
N2 - Irritability in pediatric samples is associated with higher rates of subsequent suicide-related outcomes. No study, to date, has evaluated the longitudinal association between irritability and suicidal ideation (SI) in adults with major depressive disorder (MDD). This report evaluated whether irritability is associated with SI at the same visit (i.e., concurrently) and whether early changes in irritability with antidepressant treatment predict subsequent levels of SI. Participants of Combining Medications to Enhance Depression Outcomes (CO-MED, n = 665), Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC, n = 296), and Suicide Assessment Methodology Study (SAMS, n = 266) were included. Repeated-measures mixed model analyses evaluated concurrent association throughout the trial between irritability (five-item irritability domain of Concise Associated Symptom Tracking scale) and SI (three-item suicidal thoughts factor of Concise Health Risk Tracking scale) after controlling for overall depression (excluding suicidality-related item), and predicted subsequent levels of SI (repeated observations from week-2-to-week-8) based on early (baseline-to-week-2) changes in irritability after controlling for early changes in overall depression. Higher irritability was associated with higher SI concurrently; estimates (standard error) were 0.18 (0.02, p < 0.0001), 0.64 (0.02, p < 0.0001), and 0.26 (0.04, p < 0.0001) in CO-MED, EMBARC, and SAMS respectively. Greater baseline-to-week-2 reductions in irritability predicted lower levels of subsequent SI; estimates (standard errors) were −0.08 (0.03, p = 0.023), −0.50 (0.05, p < 0.0001), and −0.12 (0.05, p = 0.024) in CO-MED, EMBARC, and SAMS, respectively. Controlling for anxiety or insomnia produced similar results. In conclusion, irritability and SI were consistently linked in adults with MDD. These findings support careful assessment of irritability in suicide risk assessment.
AB - Irritability in pediatric samples is associated with higher rates of subsequent suicide-related outcomes. No study, to date, has evaluated the longitudinal association between irritability and suicidal ideation (SI) in adults with major depressive disorder (MDD). This report evaluated whether irritability is associated with SI at the same visit (i.e., concurrently) and whether early changes in irritability with antidepressant treatment predict subsequent levels of SI. Participants of Combining Medications to Enhance Depression Outcomes (CO-MED, n = 665), Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC, n = 296), and Suicide Assessment Methodology Study (SAMS, n = 266) were included. Repeated-measures mixed model analyses evaluated concurrent association throughout the trial between irritability (five-item irritability domain of Concise Associated Symptom Tracking scale) and SI (three-item suicidal thoughts factor of Concise Health Risk Tracking scale) after controlling for overall depression (excluding suicidality-related item), and predicted subsequent levels of SI (repeated observations from week-2-to-week-8) based on early (baseline-to-week-2) changes in irritability after controlling for early changes in overall depression. Higher irritability was associated with higher SI concurrently; estimates (standard error) were 0.18 (0.02, p < 0.0001), 0.64 (0.02, p < 0.0001), and 0.26 (0.04, p < 0.0001) in CO-MED, EMBARC, and SAMS respectively. Greater baseline-to-week-2 reductions in irritability predicted lower levels of subsequent SI; estimates (standard errors) were −0.08 (0.03, p = 0.023), −0.50 (0.05, p < 0.0001), and −0.12 (0.05, p = 0.024) in CO-MED, EMBARC, and SAMS, respectively. Controlling for anxiety or insomnia produced similar results. In conclusion, irritability and SI were consistently linked in adults with MDD. These findings support careful assessment of irritability in suicide risk assessment.
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U2 - 10.1038/s41386-020-0769-x
DO - 10.1038/s41386-020-0769-x
M3 - Article
C2 - 32663842
AN - SCOPUS:85087856134
SN - 0893-133X
VL - 45
SP - 2147
EP - 2154
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 13
ER -