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

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.