Objective: Summarize the available data for the mortality risk associated with Parkinson’s disease (PD) psychosis (PDP) and pimavanserin.

Background: PDP is associated with increased mortality compared with PD without psychosis. For PDP, an observed mortality rate of 28.2 per 100 patient-years (95% CI, 27.5–28.8) has been reported. Atypical antipsychotics (AAPs) used off label to treat PDP symptoms can increase the risk of mortality; >2-fold increases in risk have been reported. Pimavanserin is a selective 5-HT_2A inverse agonist/antagonist that is currently the only FDA-approved medication for hallucinations and delusions associated with PDP.

Method: This narrative review describes mortality data of pimavanserin in the treatment of PDP from one open-label extension study, 5 retrospective studies, and postmarketing analysis (based on events reported from April 29, 2016–April 28, 2021).

Results: In the open-label extension study, the observed mortality rate was 6.45 deaths per 100 patient-years. In a retrospective study of PD patients (N=2994), mortality rates were similar for pimavanserin vs untreated patients (odds ratio, 1.2; 95% CI, 0.35– 3.13). A retrospective cohort study of PD patients (N=21,725) found lower all-cause mortality rates with pimavanserin compared with AAPs (hazard ratio, 0.78; 95% CI, 0.67–0.91). Findings reported in 2 additional retrospective studies were consistent. A retrospective study of PD patients in long-term care (N=20,398) reported increased 90-day mortality with pimavanserin vs nonuse (adjusted hazard, 1.20; 95% CI, 1.02–1.41). In the postmarketing analysis, the overall cumulative mortality rate of pimavanserin was 15.40 per 100 patient-years (95% CI, 14.97–15.85), with a minimum of 41,218 patients (30,426 patient-years) exposed. Reported causes of death reflect common comorbidities and underlying conditions of an elderly PDP population (eg, PD, disease progression, dementia, pneumonia, and respiratory and cardiac events).

Conclusion: The mortality risk associated with pimavanserin has remained consistent over time, supporting the established benefit/risk profile of pimavanserin for the treatment of PDP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-risk-of-mortality-and-antipsychotics-in-parkinsons-disease-related-psychosis-pimavanserin-vs-off-label-antipsychotics/