Association of Relapse With All-Cause Mortality in 32,071 Adults With Stable Schizophrenia: A Longitudinal Commercial and Medicare Database Study

Background: Relapse in schizophrenia adversely affects patient outcomes, yet its influence on mortality is not well characterized.

Methods: This longitudinal commercial and Medicare database study evaluated the association of relapse with all-cause mortality. Eligible adults had ≥2 outpatient claims on separate dates or ≥1 inpatient claim with a schizophrenia diagnosis, had ≥12 months of continuous pre-index enrollment without a relapse, and received ≥1 antipsychotic medication during the 12-month baseline period. Occurrence and number of inpatient and non-inpatient relapse events and all-cause mortality were evaluated during follow-up. A marginal structural model adjusting for baseline and time-varying confounding factors was used to estimate hazard ratios (HRs) and 95% CIs.

Results: Mean patient age at index 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 months, 3974 of 32,071 (12.4%) patients died and 9170 (28.6%) experienced a relapse. 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 all-cause mortality hazard by approximately 20%. Hazard of all-cause mortality was 163% greater for relapse 10 versus no relapse (HR, 2.63 [95% CI: 2.02–3.42]). Estimated 5-year survival was 78% in patients with one relapse and only 58% in patients with 10 relapses.

Conclusions: The observed increase in all-cause mortality associated with schizophrenia relapse underscores the need for increased attention to relapse prevention, including greater utilization of effective treatment strategies.