OBJECTIVE: To summarize the US Food and Drug Administration's (FDA's) review of 
the safety and effectiveness for pimavanserin, an atypical antipsychotic, for 
the treatment of hallucinations and delusions associated with Parkinson's 
disease psychosis. We describe the regulatory and clinical issues important to 
the FDA's approval of this New Drug Application, with special focus on the 
risk-benefit balance. We also describe a new labeling feature that presents 
additional efficacy data to clinicians.
DATA SOURCES: Data sets for all relevant clinical trials of pimavanserin and the 
Applicant's and FDA's analyses of these data were considered in this review. 
Data were available from 616 patients with Parkinson's disease with 
hallucinations and delusions who received at least 1 dose of pimavanserin, with 
a total exposure of 825 patient-years in the Parkinson's disease psychosis 
population.
RESULTS: Pimavanserin 34 mg/d was effective in treating hallucinations and 
delusions associated with Parkinson's disease. In the Applicant's single pivotal 
trial, 80.5% of pimavanserin patients experienced at least some improvement in 
symptoms compared to 58.1% of patients taking placebo. Pimavanserin did not 
worsen motor function, an adverse effect commonly observed with other 
antipsychotics, probably because of a lack of consequential dopamine binding.
CONCLUSIONS: Pimavanserin is the only FDA-approved treatment for the 
hallucinations and delusions seen in patients with psychosis of Parkinson's 
disease. Although pimavanserin appears to have a pharmacologic mechanism that is 
different from other atypical antipsychotics, concern remained that the 
increased risk of death seen with antipsychotic use in elderly demented 
patients, and described in all approved antipsychotic labels, would also occur 
with pimavanserin. Pimavanserin bears the same boxed warning about the risk of 
death associated with antipsychotic use in elderly patients with dementia.