Objective: An SLR was conducted to assess the evidence from RCTs supporting the safety and efficacy of Parkinson’s disease psychosis (PDP) treatments.

Background: PDP is a distinct condition characterized by hallucinations and delusions that develop after a diagnosis of PD. Other SLRs in this area focus on single drugs or do not reflect more recent RCTs.

Methods: MEDLINE, Embase, and Cochrane Library were systematically searched, and ClinicalTrials.gov was manually searched. RCTs of any pharmacological intervention for PD patients with PDP or with hallucinations and delusions published after 1990 were eligible for inclusion. Two reviewers screened titles and abstracts and then reviewed full-text of potentially relevant articles. Dual data extraction was conducted, with discrepancies adjudicated by a third researcher. Study quality and risk of bias were systematically assessed.

Results: 1,094 publications were screened, 97 progressed to full-text screening and 29 articles or registry entries, representing 23 unique trials, proceeded to data extraction. Clozapine (CLZ) appeared in 8 studies, quetiapine (QTP) in 7, olanzapine (OLN) in 5, and pimavanserin (PIM) in 4. Ziprasidone, galantamine, rivastigmine, risperidone, and melperone each appeared in 1 study. Six studies used CLZ as a comparator and 16 were placebo controlled. Trials were short (4 to 24 weeks) with 10 lasting ≤6 weeks. Brief Psychiatric Rating Scale was collected in 11 studies, and the Scale for the Assessment of Positive Symptoms or its subscales were collected in 8. Evidence from placebo controlled RCTs supports the efficacy of CLZ (2 trials, 60 randomized each) and PIM (199 randomized). QTP showed efficacy over placebo in a single, small RCT (16 randomized) but 3 other trials found no difference between QTP and placebo. In head-to-head trials of CLZ versus QTP, CLZ was superior in reducing symptoms of psychosis in 1 study and efficacy did not differ between the drugs in 2 other studies. CLZ, QTP, and PIM had no effect on motor symptoms, while OLN worsened such symptoms.

Conclusions: Our findings are consistent with CLZ and PIM PDP marketing authorizations in Europe and the US, respectively. Interpretation of most other studies was limited by small sample size and high drop-out rates. Study quality, including risk of bias, was difficult to assess, with allocation concealment and randomization methodology often not reported.

References: Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. The Lancet. 2014;383(9916):533-540.

Friedman J, Lannon M, Comella C, et al. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl j Med. 1999;1999(340):757-763.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-of-parkinsons-disease-psychosis-a-systematic-review-of-rcts/