Title: Pimavanserin for Parkinson’s Disease Psychosis: A Meta-analysis of Placebo-controlled Randomized Trials (P3-17.013)
Authors: Matthew George Petruncio, Jamir Pitton Rissardo, Omar Elmandouh, Ana Leticia Fornari Caprara, and Ian M. Walker
Conference: 2026 AAN, Chicago, IL
Objective
To evaluate the efficacy and safety of pimavanserin in Parkinson’s disease psychosis (PDP) through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).
Background
Psychosis affects up to 60% of Parkinson’s disease patients and is associated with increased caregiver burden. Pimavanserin is the only FDA-approved drug for PDP, but its risk-benefit profile remains debated.
Design/Methods
RCTs comparing pimavanserin with placebo were identified via systematic search. The primary outcome was psychosis severity by SAPS-PD or SAPS-H+D. Secondary outcomes included UPDRS II/III and adverse events such as falls, orthostatic hypotension, and confusional state. Random-effects models were used to calculate standardized mean differences (SMD)
Results
Four trials (PMID 19907417, NCT01174004, NCT00477672, NCT00658567) were included. Pimavanserin significantly reduced psychosis severity (SMD −0.70; 95% CI −0.86 to −0.55; p < 0.01). Motor function showed no significant change (UPDRS II/III: MD −0.08; 95% CI −1.55 to 1.39; p = 0.92). Most adverse events were not significantly different from placebo, including falls (RR 0.69; 95% CI 0.42–1.12), hallucinations (RR 0.96; 95% CI 0.24–3.81), headache (RR 0.58; 95% CI 0.28–1.21), and confusional state (RR 1.42; 95% CI 0.67–3.02). Risk of orthostatic hypotension was lower with pimavanserin (RR 0.36; 95% CI 0.17–0.76). Heterogeneity was high for efficacy outcomes (I² > 90%) but low for safety outcomes.
Conclusions
Pimavanserin significantly improves psychosis in PDP without worsening motor symptoms. Most adverse events, including confusion, were not significantly different from placebo, except for a possible reduction in orthostatic hypotension. High heterogeneity and wide prediction intervals warrant cautious interpretation and further head-to-head trials.
Citation
Petruncio MG, Rissardo JP, Elmandouh O, Caprara AL, Walker IM. Pimavanserin for Parkinson’s Disease Psychosis: A Meta-analysis of Placebo-controlled Randomized Trials (P3-17.013). Neurology 2026;106(11_suppl):1176. doi: 10.1212/WNL.0000000000215026.
Figure 1. Forest plot shows pimavanserin reduces psychosis severity versus placebo in PDP, with substantial heterogeneity across trials.