Association of Relapse With All-Cause Mortality in Adult Patients With Stable Schizophrenia

Abstract Background Schizophrenia shortens the average lifespan by an estimated 15 years. This retrospective study evaluated whether relapse independently increases all-cause mortality risk in patients with stable schizophrenia. Methods Eligible adults had ≥2 outpatient claims on separate dates or ≥1 inpatient claim with a schizophrenia diagnosis code, had ≥12 months of continuous pre-index enrollment without a relapse, and received ≥1 antipsychotic medication during the baseline period. Occurrence and number of inpatient and non-inpatient relapses and all-cause mortality were evaluated during follow-up. A marginal structural model adjusting for both baseline and time-varying confounding was used to estimate hazard ratios (HRs) and 95% CIs. Results Mean age at index of the 32,071 patients included in the analysis was 57.6 (SD, 15.3) years; 51.0% of patients were male and 55.4% were White. During a mean follow-up of 40 (range, 1–127) months, 3974 (12.4%) patients died. Of the 9170 (28.6%) patients with relapse(s) during follow-up, most experienced one (53.4%) or two (20.0%) relapses. After adjustment for covariates, the HR for all-cause mortality was significantly higher for patients with one relapse versus no relapses (1.20 [95% CI: 1.14–1.26]). For the first five relapses, each subsequent relapse increased allcause mortality hazard by approximately 20%. Estimated 5-year survival was 78% in patients with one relapse and 58% in patients with 10 relapses. Conclusions The observed increase in all-cause mortality associated with schizophrenia relapse underscores the need for heightened attention to relapse prevention, including greater utilization of effective treatment strategies early in the course of disease.