# Sedation and sleep safety of pimavanserin for Parkinsons’s disease psychosis: Review and exploratory analysis of clinical study data

## TL;DR

This paper reviews clinical data on pimavanserin's effects on sleep and sedation in Parkinson's disease psychosis patients.

## Contribution

The paper provides an exploratory analysis of pimavanserin's sleep-related safety compared to other antipsychotics.

## Key findings

- Pimavanserin is associated with low levels of sleep-related adverse events.
- Pimavanserin may improve nighttime sleep in Parkinson's disease psychosis patients.
- Head-to-head trials are needed to compare pimavanserin with other antipsychotics.

## Abstract

•This review summarizes pimavanserin sleep-related safety data from clinical trials.•Pimavanserin may be associated with low levels of sleep‑related adverse events.•Pimavanserin may also be associated with an improvement in nighttime sleep.•Head-to-head trials are needed to compare pimavanserin with other antipsychotics.

This review summarizes pimavanserin sleep-related safety data from clinical trials.

Pimavanserin may be associated with low levels of sleep‑related adverse events.

Pimavanserin may also be associated with an improvement in nighttime sleep.

Head-to-head trials are needed to compare pimavanserin with other antipsychotics.

Patients with Parkinson’s disease almost uniformly experience sleep disorders. Sleep disorders have been linked to the severity of cognitive impairment, which is also a comorbidity with Parkinson’s disease psychosis (PDP). Pimavanserin, a highly selective inverse agonist of the serotonin 2A receptor, is approved in the United States for the treatment of hallucinations and delusions in patients with PDP. Other atypical antipsychotics, such as quetiapine and clozapine, are frequently used off-label to treat PDP and have an increased risk of sedation and other sleep-related adverse events (eg, drowsiness, sedation). By contrast, a high degree of specificity for the serotonin 2A receptor may prevent pimavanserin from causing some of the off-target adverse events associated with other atypical antipsychotics. In this review and exploratory analysis, we summarize pimavanserin sleep- and sedation-related safety and tolerability data from past clinical trials, including 6 randomized controlled trials and 2 open-label extensions representing various pimavanserin doses (1 to 51 mg) in healthy volunteers, patients with PDP, and older patients with neurodegenerative disease. The results from our exploratory analyses suggest that pimavanserin may be associated with negligible levels of sedation and other sleep‑related adverse events and may provide improvements in nighttime sleep compared with placebo. Future head-to-head clinical trials will be needed for direct comparisons between pimavanserin and other atypical antipsychotics, such as quetiapine or clozapine.