Psychosis is a common neuropsychiatric symptom associated with Parkinson's disease (PD), with prevalence rates of up to 75%. 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 antipsychotics for PDP is common, with up to 35% of PD patients prescribed at least one antipsychotic within 7 years of PD diagnosis. This systematic literature review aims to search, appraise and synthesise the best available and most up-to-date evidence for the use of antipsychotics in the treatment of PDP, and their effects on PD motor symptoms.

We carried out a comprehensive literature review and meta-analysis following the PRISMA statement for systematic reviews.

Four studies investigated quetiapine, three investigated olanzapine, two investigated clozapine and a further two investigated pimavanserin. Both quetiapine and olanzapine showed no significant improvement for PDP over placebo, however meta-analysis of olanzapine groups showed significant motor worsening, UPDRS +2.89 (95% CI 1.22 to 4.56) compared with placebo. Clozapine showed a significant improvement in psychosis vs placebo in both studies, with a large effect size in their primary outcome measure; -0.82 (95% CI -1.37 to -0.26), -0.89 (95% CI -1.42 to - 0.36). Pimavanserin showed significant improvement in psychosis vs placebo -0.48 (95% CI -0.77 to -0.18). Quetiapine, clozapine and pimavanserin showed no significant worsening in motor scores vs placebo group.

Although Olanzapine and Quetiapine are commonly used to treat psychotic symptoms in Parkinson's Disease, the only medication with robust evidence is Clozapine. This finding may have implications for service delivery.