Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis

Han Zhang,*,1 Limin Wang,*,2 Yafei Fan,1 Lianhong Yang,1 Xiaojun Wen,3 Yunyun Liu,4 Zhonglin Liu11Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People’s Republic of China; 2Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou 510080, Guangdong Province, People’s Republic of China; 3Department of Neurology, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou-Birmingham University Brain and Cognition Center, Guangzhou 510180, People’s Republic of China; 4Department of Neurology, The Sixth Affiliated Hospital Sun Yat-Sen University, Guangzhou 510440, People’s Republic of China*These authors contributed equally to this workPurpose: To assess the present evidence regarding the efficiency, safety, and potential risks of pharmacotherapy used for Parkinson’s disease psychosis (PDPsy) treatment.Patients and methods: We searched the following databases: PubMed, the Cochrane Library, ISI Web of Science, and Embase using the following terms: atypical antipsychotics, pimavanserin, olanzapine, quetiapine, clozapine, Parkinson’s disease and psychosis. We systematically reviewed all randomized placebo-controlled trials comparing an atypical antipsychotic with a placebo.Results: A total of 13 randomized placebo-controlled trials for a total 1142 cases were identified involving pimavanserin (n=4), clozapine (n=2), olanzapine (n=3), and quetiapine (n=4). For each atypical antipsychotic, a descriptive synthesis and meta-analyses was presented. Pimavanserin was associated with a significant improvement in psychotic symptoms compared to a placebo without worsening motor function. Clozapine was efficacious in alleviating psychotic symptoms and did not exacerbate motor function either. Quetiapine and Olanzapine did not demonstrate significant differences in reducing psychotic symptoms but may aggravate motor function.Conclusions: There is strong evidence that pimavanserin is effective for the treatment of PDPsy. Clozapine is also recommended but should be used with caution due to its side effects. In the future, more well-designed randomized controlled trials (RCTs) are needed to confirm and update the findings reported in this meta-analysis.Keywords: clinical trials systematic review/meta-analysis, psychosis, Parkinson’s disease/Parkinsonism