Association of relapse with all-cause mortality in adult patients with stable schizophrenia

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 1 (53.4%) or 2 (20.0%) relapses. After adjustment for covariates, the HR for all-cause mortality was significantly higher for patients with 1 relapse vs no relapses (1.20 [95% CI, 1.14-1.26]). For the first 5 relapses, each subsequent relapse increased all-cause mortality hazard by approximately 20%. Estimated 5-year survival was 78% in patients with 1 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.