Retrospective analyses evaluating the mortality risk associated with pimavanserin or other atypical antipsychotics in patients with Parkinson disease psychosis

Introduction: Parkinson 's disease (PD) is associated with increased mortality risk (MR), reflecting progression of motor and nonmotor symptoms. PD psychosis (PDP), a common nonmotor symptom, increases with prolonged disease and elevates the MR of PD even further. Pimavanserin is the only FDA -approved treatment for PDP. This review summarizes real -world evidence around the MR of patients with PDP treated with pimavanserin versus off -label atypical antipsychotics. Methods: A PubMed search was conducted using the following search terms: pimavanserin AND antipsychotic AND mortality AND Parkinson 's disease AND psychosis . Inclusion criteria specified the entry of retrospective, observational, and open -label studies comparing pimavanserin to atypical antipsychotics or untreated controls. Results: A total of 10 of the 32 articles met inclusion criteria. Among five comparisons of pimavanserin with atypical antipsychotics, two were large (n = 21,719; n = 21,975), representative, Medicare -database studies, which demonstrated comparable or lower all -cause pimavanserin MR. Among three pimavanserin versus control studies, two reported lower or comparable pimavanserin MR and one, long-term care study reported higher MR for pimavanserin versus non-pimavanserin treated patients with unknown PDP status. Two open -label extensions reported pimavanserin mortality rates of 6.45 and 18.8 deaths per 100 patient -years, which are comparable to, or lower than, mortality rates for PD, PDP, and other atypical antipsychotics. Most studies (70 %; 7 of 10) demonstrated pimavanserin 's MR was lower than or similar to other atypical antipsychotics or untreated controls. Conclusions: Pimavanserin did not increase the MR in PDP. Pimavanserin 's MR appears to be comparable to or lower than other atypical antipsychotics prescribed for PDP, including quetiapine.