Nuplazid increases risk for death in older adults with Parkinson’s disease

Older adults with Parkinson’s disease who used Nuplazid had increased risk for hospitalization and death at certain timepoints after initiation compared with nonusers, according to study results published in Neurology.

“Typical and atypical antipsychotics were previously associated with increased risks for death in patients with PD,” Y. Joseph Hwang, MD, MSc, assistant professor of medicine in the department of medicine at Johns Hopkins University, told Healio Neurology. “We designed this study to evaluate such risks associated with pimavanserin [Nuplazid, Acadia Pharmaceuticals], a novel antipsychotic approved for PD psychosis.”

Hwang and colleagues conducted the current retrospective cohort study to assess the risk for hospitalization and death linked to pimavanserin use among adults 65 years or older with PD between Nov. 1, 2015, and Dec. 31, 2018. They obtained data via an administrative dataset on residents of Medicare-certified long-term care facilities and linked Medicare claims data.

The researchers balanced pimavanserin users (n = 2,186) and nonusers (18,212) according to 24 baseline characteristics using propensity score-based inverse probability of treatment weighting (IPTW). They used hazards regression models to estimate the risk for hospitalization and death up to 1 year.

Results showed an association between pimavanserin use and higher risk for 30-day hospitalization compared with nonuse (IPTW adjusted HR = 1.24; 95% CI, 1.06-1.43). Hwang and colleagues observed no association between pimavanserin use and 90-day hospitalization (aHR = 1.1; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR = 0.76; 95% CI, 0.56-1.03); however, they noted an association between pimavanserin use vs. nonuse and increased 90-day mortality (aHR = 1.2; 95% CI, 1.02-1.41) that persisted after 180 days (aHR = 1.28; 95% CI, 1.13-1.45) and 1 year (aHR = 1.56; 95% CI, 1.42-1.72).

“Our findings may inform clinical decisions when considering risks and benefits of pharmacotherapy for [PD] psychosis,” Hwang said.

In a related editorial, Farwa Ali, MBBS, a neurologist at Mayo Clinic, highlighted the implications of these findings.

“The study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in PD psychosis, clear communication with patients and families and close observation to ensure safety,” Ali wrote.