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Background Relapse is common in major depressive disorder (MDD). In this study, we evaluated the incremental health care burden of relapse in patients with MDD. Methods This real-world retrospective cohort study used administrative medical and pharmacy claims data to identify commercially insured adult patients in the United States diagnosed with MDD who initiated a new antidepressant between January 1, 2012, and September 30, 2017. All-cause health care resource utilization, total costs, and medication adherence were evaluated in two cohorts: patients with and patients without relapse. Relapse was defined as suicide attempts, psychiatric hospitalization, mental health–related emergency department (ED) visit, use of electroconvulsive therapy, or reinitiation of treatment after a gap ≥6 months. Results The study population included 14,186 patients (7093 baseline-matched patients per cohort). The mean follow-up period was 27.5 and 26.0 months for patients with and patients without relapse, respectively. Patients with relapse had significantly higher rates of hospitalization (16.6% vs 8.5%;  p &lt;  .0001) and ED visits (54.8% vs 34.7%;  p &lt;  .0001) than patients without relapse. The total costs for patients with relapse were significantly higher ($12,594 vs $10,445;   p &lt;  .0001). Patients with relapse were also less adherent to antidepressants (mean proportion of days covered, 0.43 vs 0.49;  p &lt;  .0001). Conclusions Relapse of MDD was associated with increased total costs and health care utilization and lower adherence to antidepressants. Reducing the risk of relapse may result in a reduction of the associated health care burden; however, findings may only be generalizable to patients with commercial insurance.

Incremental burden of relapse in patients with major depressive disorder: a real-world, retrospective cohort study using claims data