Abstract
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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Study design: MHT. Obtained funding: MT. Data acquisition: MKJ and MT. Data analysis: AM. Data interpretation: MKJ, AM, CCF, KK, AS, EL, and MT. Drafting of the work: MKJ. Revising paper critically for important intellectual content: MKJ, AM, CCF, KK, AS, Leibenluft, MT. Final approval: MKJ, AM, CCF, KK, AS, EL, and MT. The design of CO-MED, EMBARC and SAMS was led by MT. MKJ and MT contributed substantially to the acquisition of data. AM completed the data analysis. MKJ, AM, CCF, KK, AS, EL, and MT contributed to the interpretation of data. MKJ drafted the initial paper and all authors revised paper critically for important intellectual content. All authors provided the final approval to the submitted version and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Findings of this report were presented in part at the 2019 Annual Meeting of American College of Neuropsychopharmacology.
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Jha, M.K., Minhajuddin, A., Chin Fatt, C. et al. Association between irritability and suicidal ideation in three clinical trials of adults with major depressive disorder. Neuropsychopharmacol. 45, 2147–2154 (2020). https://doi.org/10.1038/s41386-020-0769-x
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DOI: https://doi.org/10.1038/s41386-020-0769-x
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