Mortality in Patients with Parkinson’s Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study

Introduction Pimavanserin is approved in the USA to treat hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Objectives We evaluated mortality in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics, overall, over time, and across subgroups. Methods A cohort of patients aged ≥65 years in the USA with PDP newly initiating pimavanserin or a comparator atypical antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) was identified in 2016–2019 Medicare claims data. All-cause mortality in the propensity score–matched treatment groups was compared with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated with Cox-proportional hazards models. Cumulative incidence curves and time period–specific models evaluated risk over time. Subgroup and sensitivity analyses were performed, including a sub-cohort of long-term care (LTC) or skilled nursing facility (SNF) residents. Results We identified 2892 pimavanserin initiators and 19,083 comparator initiators (overall 47% female, mean age = 80.9 years, LTC/SNF residents = 30%). Before matching, pimavanserin users had fewer severe comorbidities and more anti-Parkinson medication use than comparators. Matching resulted in 2891 patients in both groups, and all covariates were well balanced. In the matched cohort, the HR for mortality for pimavanserin versus comparator was 0.78 (95% CI 0.67–0.91), with the lowest time period–specific HRs in the first 180 days. Hazard ratios were similar across sensitivity analyses and subgroups. In LTC/SNF residents, the HR was 0.78 (95% CI 0.60–1.01). Conclusion The observed mortality rates were lower among patients treated with pimavanserin compared with those treated with other atypical antipsychotics. Study registration European Union Post-authorization Study (EU PAS) register number 46331.