Early reduction in irritability is associated with improved outcomes among youth with depression: Findings from the AMOD study

Objectives: Evaluate whether early improvement in irritability predicts improvement in depression severity in a naturalistic sample of adolescents undergoing pharmacologic treatment for major depressive disorder. Methods: Adolescents (N = 161) aged 13–18 years with a moderate to severe depressive episode were enrolled. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R), Quick Inventory of Depressive Symptomatology (QIDS-A₁₇), and Clinical Global Impression scale (CGI). Paired t-tests were used to estimate the change in irritability items from baseline to week-4, and Cohen's d effect sizes were computed. Separate linear regression analyses with CDRS-R, QIDS-A₁₇, and CGI at week-8 as the dependent variables and baseline levels of irritability and baseline-to-week-4 changes in irritability as independent variables of interest were conducted. These analyses were repeated after controlling for overall depression severity (minus the irritability item) at baseline and baseline to week-4 change. Results: Greater baseline to week-4 reduction in irritability was associated with lower levels of CDRS-R, QIDS-A₁₇, and CGI at week-8. These findings were significant for QIDS-A₁₇ and CGI even after controlling for baseline-to-week-4 changes in other depressive symptoms. Limitations: The single item evaluation of irritability reduced assessment reliability in the absence of validated measures of irritability. Conclusions: Early reduction in irritability is strongly associated with better outcomes in depressed youths, regardless of baseline depression severity. Further research is needed to quantify the burden of irritability, explore it as a tool for measurement-based care, and to develop targeted treatments for irritability.