# Antipsychotic Medications in Parkinson’s Disease Psychosis; A Systematic Review of Double-Blind, Randomised, Placebo-Controlled Trials

## TL;DR

This review finds that clozapine is effective for Parkinson’s disease psychosis, while quetiapine lacks strong evidence for its use.

## Contribution

The study systematically evaluates antipsychotic medications for Parkinson’s disease psychosis using randomized, placebo-controlled trials.

## Key findings

- Clozapine improves Parkinson’s disease psychosis with large effect sizes at low doses and does not worsen motor function.
- Quetiapine has limited evidence for treating Parkinson’s disease psychosis despite frequent clinical use.
- Pimavanserin also shows significant improvement in psychosis symptoms without worsening motor scores.

## Abstract

Main findings
Clozapine shown to improve Parkinson’s disease psychosis (PDP) with a large effect size despite low doses and does not appear to worsen motor function.Quetiapine has a poor evidence base for treatment of PDP, despite widespread use.

Clozapine shown to improve Parkinson’s disease psychosis (PDP) with a large effect size despite low doses and does not appear to worsen motor function.

Quetiapine has a poor evidence base for treatment of PDP, despite widespread use.

Implications
Clozapine could be considered as a first line antipsychotic (AP) for the management of PDP if standard reductions in dopaminergic medications fail to achieve resolution of symptoms.APs with low Dopamine receptor 2 (D2) affinity may not appreciably worsen motor symptoms of Parkinson’s Disease.

Clozapine could be considered as a first line antipsychotic (AP) for the management of PDP if standard reductions in dopaminergic medications fail to achieve resolution of symptoms.

APs with low Dopamine receptor 2 (D2) affinity may not appreciably worsen motor symptoms of Parkinson’s Disease.

Background: Psychosis is a common neuropsychiatric symptom associated with Parkinson’s disease (PD), with prevalence rates of up to 75% over the course of the disease. Parkinson’s disease psychosis (PDP) is associated with increased morbidity, caregiver burden, depression, poorer quality of life and progression of dementia. It has also been shown to be a strong predictive factor for long-term care placement, and results in up to 71% increase in risk of mortality compared with PD patients free from psychotic symptoms. Use of APs for PDP is common, with up to 35% of PD patients prescribed at least one AP within 7 years of PD diagnosis. Methods: Four electronic databases (Ovid MEDLINE, Embase, PsycINFO, PubMed) were systematically searched for double-blind, randomised, placebo-controlled clinical trials for the use of APs in the treatment of PDP and their effects on PD motor symptoms, according to PRISMA guidelines. Results: Eleven studies from ten publications were identified and included in this review. Four studies investigated quetiapine, three investigated olanzapine, two investigated clozapine and a further two investigated pimavanserin. Quetiapine showed no significant improvement for PDP over placebo in three of the four studies, with both olanzapine studies also showing no improvement. Olanzapine studies also showed significant motor worsening compared to placebo. Clozapine significantly improved psychosis compared with placebo in both studies, with large effect sizes in primary outcome measures; (−0.82, 95% CI −1.37 to −0.26), −0.89 (95% CI −1.42 to −0.36). Pimavanserin also showed significant improvement (−0.48, 95% CI −0.77 to −0.18). Quetiapine, clozapine and pimavanserin showed no significant worsening in motor scores compared with placebo groups. Conclusions: Data from the studies included in this review suggest that the use of quetiapine for the management of PDP may not be evidence based. Clozapine may improve PDP symptoms with low doses however significant side-effects may limit usability. The findings from this review support the use of clozapine as an alternative AP for the management of PDP when clinically appropriate.