INTRODUCTION: Pimavanserin is approved in the US to treat hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). All US antipsychotic labels include boxed warnings of mortality risk in older patients with dementia-related psychosis. To compare mortality risk in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics in an overall PDP cohort and in a subcohort of patients residing in long-term care or skilled nursing facilities (LTC/SNF).
METHODS: This cohort study identified patients aged ≥65 years with PDP initiating pimavanserin or a comparator atypical antipsychotic in US Medicare claims (2016 2021). A subcohort of LTC/SNF residents was identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) comparing all-cause mortality in the propensity score–matched treatment groups. Cumulative incidence curves, time period–specific relative risk, and risk difference estimates evaluated risk over time.
RESULTS: This study identified 4,384 pimavanserin initiators and 28,042 comparator initiators in the overall PDP cohort and 921 pimavanserin initiators and 7,963 comparator initiators in the LTC/SNF subcohort. Before matching, pimavanserin initiators had fewer severe comorbidities and more Parkinson’s disease medication use than comparator users; after matching, all characteristics were well balanced. After matching, the overall PDP cohort had 4,381 patients in each treatment group, and the LTC/SNF subcohort had 905 patients in each group. The matched HR for mortality (pimavanserin versus comparator) was 0.76 (95% CI, 0.68-0.85) in the overall PDP cohort and 0.90 (95% CI, 0.74-1.10) in the LTC/SNF subcohort. In the overall PDP cohort, time period–specific relative risks and risk differences showed that pimavanserin initiators had a lower risk of mortality during the first 365 days of follow-up.
CONCLUSIONS: This active-comparator, new-user cohort study suggests an overall lower mortality risk in older patients with PDP treated with pimavanserin than in patients treated with other atypical antipsychotic drugs through at least the first year of treatment. No meaningful differences in mortality risk were observed between treatment groups in the LTC/SNF subcohort. Regardless of treatment group, mortality was higher in the LTC/SNF subcohort than the overall PDP cohort.
