Antipsychotics for Parkinson's disease: a protocol for a systematic review with network meta-analysis and trial sequential analysis.

Parkinson's disease is a neurological disease with a rising incidence and prevalence. Patients with Parkinson's disease may receive antipsychotics, for example, due to Parkinson's disease psychosis. Parkinson's disease psychosis is characterised by visual hallucinations and other psychotic symptoms. To date, no systematic review has evaluated the effects of antipsychotics in patients with Parkinson's disease. Therefore, this review aims to assess the beneficial and harmful effects of antipsychotics for Parkinson's disease. This is a protocol for a systematic review. A search specialist will perform a search in major medical databases (eg, MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica database), CENTRAL (Cochrane Central Register of Controlled Trials)) and clinical trial registries. Published and unpublished randomised clinical trials comparing antipsychotics to any control (placebo, standard care or other antipsychotics) in patients with Parkinson's disease will be included. Two review authors will independently extract data and conduct risk of bias assessments with the Cochrane Risk of Bias tool-V.2. Primary outcomes will be all-cause mortality, serious adverse events and significant falls. Secondary outcomes will be hospitalisations, non-serious adverse events, Unified Parkinson's Disease Rating Scale total score and psychotic symptoms using any valid symptom scale. Data will be synthesised by aggregate meta-analysis, trial sequential analysis and network meta-analysis. Several subgroup analyses are planned. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluations) and CiNeMA (Confidence in Network Meta-Analysis) approach. This protocol does not include results, and ethics approval is not required for the project. The findings from the systematic review will be published in international peer-reviewed scientific journals. PROSPERO ID: CRD42025633985. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633985.