Pimavanserin Linked to Fewer Falls Than Other Antipsychotics in Parkinson Disease Psychosis

A retrospective analysis of 100% Medicare claims data found that patients with Parkinson disease psychosis (PDP) living in long-term care and nursing home (LTC/NH) settings had significantly fewer falls and recurrent falls when treated with pimavanserin (Nuplazid) compared with other atypical antipsychotics or quetiapine.¹

Pimavanserin, a selective serotonin 2A (5-HT2A) inverse agonist, is the only agent approved by the US Food and Drug Administration (FDA) for hallucinations and delusions associated with PDP, with or without dementia.² Despite this approval, off-label use of other atypical antipsychotics such as quetiapine and olanzapine remains common for PDP. According to prior research, this practice may increase fall risk in the already vulnerable, elderly LTC/NH population.^3,4

Falls among patients with PDP in these settings are common and can lead to fall-related injuries and hospitalizations.⁵ Earlier studies already reported a lower likelihood of falls for individuals treated with pimavanserin when compared with off-label atypical antipsychotics in LTC/NH populations; this analysis extended that comparison to recurrent and new falls and added a within-patient pre- vs post-treatment assessment.^6,7

About the Retrospective Analysis

Investigators, led by researchers from Acadia Pharmaceuticals and Anlitiks Inc, identified participants with a diagnostic claim for Parkinson disease followed by psychosis who resided in LTC/NH settings (at least 100 days of admission or a verified Minimum Data Set stay) and who initiated continuous monotherapy with pimavanserin, other AAPs (aripiprazole, olanzapine, or risperidone), or quetiapine for at least 6 months between April 1, 2016, and June 30, 2021. Participants on other atypical antipsychotics or quetiapine were propensity score matched 1:1 to pimavanserin participants on age, sex, race, region, and 27 of 31 Elixhauser comorbidities, yielding 3 matched cohorts of 1385 participants each. Matched participants were approximately 79 years old, and more than half of each cohort was male; the most prevalent comorbidities were uncomplicated hypertension (approximately 58%) and depression (approximately 35%).

Falls and Recurrent Falls

In the 6 months after treatment initiation, 19.86% (n=275) of pimavanserin participants had at least 1 fall, compared with 25.27% (n=350) of both the other-AAPs and quetiapine cohorts (P<0.05 for both comparisons). Recurrent falls followed the same pattern: 7.44% (n=103) of pimavanserin participants had a recurrent fall, vs 12.85% (n=178) of the other-AAPs cohort and 12.13% (n=168) of the quetiapine cohort (P<0.05 for both).

After adjusting for index year, insomnia, dementia, and pre-index falls in log-binomial regression models, pimavanserin participants were approximately 25% less likely to have a post-index fall than those on other AAPs (adjusted relative risk [aRR], 0.75; 95% CI, 0.66-0.86) or quetiapine (aRR, 0.77; 95% CI, 0.67-0.89). The difference was more pronounced for recurrent falls, where pimavanserin participants were approximately 40% less likely to experience a recurrent fall than those on other AAPs (aRR, 0.54; 95% CI, 0.43-0.68) or quetiapine (aRR, 0.60; 95% CI, 0.48-0.76).

New falls, defined as a post-index fall claim among participants with no fall in the 6 months before treatment, were also less frequent with pimavanserin (12.71%; n=176) than with other AAPs (15.74%; n=218) or quetiapine (16.53%; n=229). In a within-cohort comparison of the 6 months before and after treatment initiation, the pimavanserin cohort's fall rate dropped significantly, from 24.04% pre-index to 19.86% post-index (P<0.05). Fall rates in the other-AAPs cohort rose numerically, from 24.26% to 25.27%, and fall rates in the quetiapine cohort were essentially unchanged, from 25.99% to 25.27%; neither within-cohort change reached statistical significance.

Limitations

The study, sponsored by Acadia Pharmaceuticals, carries limitations common to claims-based research. Because PDP has no dedicated diagnostic code, identification relied on codes for hallucinations, delusions, and psychosis, which likely underestimates the true PDP population; fall rates are also likely underestimated, since minor falls that do not prompt medical attention typically go uncaptured in claims data. Falls occurring before the 6-month pre-index window were not assessed, which the investigators note could inflate the apparent rate of new falls, and residual confounding may persist despite propensity score matching and covariate adjustment.

Next Steps

The investigators concluded that pimavanserin was associated with lower rates of falls and recurrent falls than other AAPs or quetiapine among LTC/NH residents with PDP, both in adjusted between-cohort comparisons and in the within-cohort pre-post analysis. They suggested that future research explore longer follow-up periods and additional predictive factors for falls in this population to better characterize the relationship between antipsychotic choice and fall risk in LTC/NH residents with PDP.

References

1. Rashid N, Rajagopalan K, Gopal D, Chrones L. Falls and recurrent falls among Parkinson's disease psychosis patients treated with pimavanserin versus other atypical antipsychotics in long term care/nursing home settings (poster #1). Presented at: 2026 Psych Congress; September 15-19, 2026; New Orleans, LA.

2. Nuplazid (pimavanserin). Package insert. Acadia Pharmaceuticals Inc; 2025.

3. Rissardo JP, Duarte I, Sharon I, Caprara ALF. Pimavanserin and Parkinson's disease psychosis: a narrative review. Brain Sci. 2022;12(10):1286.

4. Fraser LA, Liu K, Naylor KL, et al. Falls and fractures with atypical antipsychotic medication use: a population-based cohort study. JAMA Intern Med. 2015;175(3):450-452.

5. Quigley P, Barnett SD, Bulat T, Friedman Y. Reducing falls and fall-related injuries in medical-surgical units: one-year multihospital falls collaborative. J Nurs Care Qual. 2016;31(2):139-145.

6. Forns J, Layton JB, Bartsch J, et al. Increased risk of falls and fractures in patients with psychosis and Parkinson disease. PLoS One. 2021;16(1):e0246121.

7. Rajagopalan K, Rashid N, Gopal D, Doshi D. Falls and fractures among nursing home residents treated with pimavanserin versus other atypical antipsychotics: analysis of Medicare beneficiaries with Parkinson's disease psychosis. Drugs Real World Outcomes. 2024;11(3):441-449.