Predicting relapse with individual residual symptoms in major depressive disorder: a reanalysis of the STAR*D data

Background: Residual symptoms are detrimental to prognosis in major depressive disorder (MDD); however, little is known about the contribution of each residual symptom in predicting outcomes. The objective of this analysis was to identify which individual symptoms, based on self-report and clinician interview, could predict subsequent relapse. Methods: The data of 1133 outpatients with nonpsychotic MDD who entered a 12-month naturalistic follow-up phase after achieving remission with level 1 treatment (i.e., citalopram for up to 14 weeks) and had at least one post-baseline contact in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. Specific residual symptoms in the 16-item Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR₁₆) and clinician rating (QIDS-C₁₆), at the follow-up entry that predicted relapse were identified, using a Cox proportional hazards model. Results: The following three QIDS-SR₁₆ symptoms were significantly associated with subsequent relapse: restlessness (HR = 1.197, p = 0.018), hypersomnia (HR = 1.190, p = 0.009), and weight change (HR = 1.127, p = 0.041). On the other hand, the following three symptoms in the QIDS-C₁₆ at the follow-up entry were significantly associated with relapse in the follow-up phase: restlessness (HR = 1.328, p = 0.001), sleep onset insomnia (HR = 1.129, p = 0.047), and weight change (HR = 1.125, p = 0.045). Limitations: The original trial was not designed to evaluate the issue addressed herein. Individual symptoms may be associated with each other and functional status was not addressed. Conclusions: Some residual symptoms, including restlessness, insomnia, and weight change, may help better identify patients with MDD vulnerable to relapse. Contribution of individual residual symptoms to subsequent relapse was similar between self-report and clinician-rated symptoms.