Pimavanserin Tied to Increased Mortality in Older Adults With Parkinson Disease

Neurodegenerative disease concept illustration. Alzheimer’s, Parkinson’s disease concept 3d illustration.
Researchers sought to determine the risk of hospitalization and death associated with pimavanserin use, a novel antipsychotic medication, in adult patients 65 years and older with Parkinson disease.

Patients with Parkinson disease (PD) who are treated with pimavanserin, a novel antipsychotic medication, have a higher risk of hospitalization after 1 month of use and an increased risk of mortality at up to 1 year following treatment initiation, according to study results published in Neurology.

The U.S. Food and Drug Administration (FDA) approved pimavanserin to help manage hallucinations and delusions in patients with PD. Previous studies have found an unfavorable trend in deaths among patients who use this drug. Research has demonstrated typical and atypical antipsychotics are likely to more than double the risk for death in this population group.

The current objective of this study was to assess the risk of hospitalization and death tied to pimavanserin use in older adults with PD.

The retrospective study included patients with PD aged ≥65 years, including 2186 patients who used pimavanserin and 18,212 nonusers. Patient data were obtained from administrative dataset that included residents of Medicare-certified long-term care facilities, in addition to linked Medicare claims data.

Users and nonusers of pimavanserin were balanced on a total of 24 baseline characteristics with propensity score-based inverse probability of treatment weighting (IPTW). Researchers estimated the risk of hospitalization and death up to 1 year using Fine-Gray competing risk and Cox proportional hazards regression models, respectively.

According to the estimates, patients who used pimavanserin had a higher risk of 30-day hospitalization compared with nonusers (IPTW adjusted hazard ratio [aHR], 1.24; 95% CI, 1.06–1.43). In contrast, there was no association between pimavanserin treatment and hospitalization at 90 days (aHR, 1.10; 95% CI, 0.99–1.24) or mortality at 30 days (aHR, 0.76; 95% CI, 0.56–1.03).

However, patients who used pimavanserin had an increased risk of 90-day mortality (aHR 1.20, CI 1.02–1.41) compared with nonusers, and this associated risk persisted after a full 180 days (aHR, 1.28; 95% CI, 1.13–1.45) and up to 1 year (aHR, 1.56; 95% CI, 1.42–1.72).

A limitation of the study included its observational nature, which the researchers suggest subject the findings to residual confounding. Additionally, given the study comprised of long-term care residents with PD, the investigators note the findings may not be generalizable across community-dwelling older adults or patients who have received pimavanserin for other conditions.

Despite these limitations, the researchers concluded that the “findings may inform risk-benefit consideration and clinical decisions among” patients with advanced PD.


Hwang YJ, Alexander GC, An H, et al. Risk of hospitalization and death associated with pimavanserin use in older adults with Parkinson disease. Neurology. Published online August 13, 2021. doi:10.1212/WNL.0000000000012601