Risk of agranulocytosis and neutropenia in patients with Parkinson's disease psychosis receiving clozapine treatment: A systematic review and meta-analysis

Objective: To assess the cumulative incidence of severe neutropenia and agranulocytosis (SNA) and mild and moderate neutropenia (MMN) in patients with Parkinson's disease psychosis (PDP) who receive clozapine treatment. Methods: We searched multiple databases to identify clozapine studies in PDP patients. Incidence rates were assessed during short-term (within 1 month), medium-term (within 6 months), and long-term (> 6 months) monitoring periods. A proportional meta-analysis was performed using random-effects and generalized linear mixed models (GLMMs). Results: We included 691 PDP patients from 19 studies. During the short-term monitoring period, none of the 573 participants in 16 studies developed SNA. The pooled incidence of SNA was 0.001 (95 % confidence interval [CI]: 0.000-0.253, 525 participants, 15 studies) during the medium-term period and 0.002 (95 % CI: 0.000-0.015, 475 participants, 12 studies) during the long-term period. The pooled incidence of MMN was 0.004 (95 % CI: 0.000-0.281, 164 participants, 7 studies) for short- and medium-term periods and 0.013 (95 % CI: 0.002-0.094, 193 participants, 7 studies) in the long-term period. Funnel plot asymmetry indicated potential bias in the medium-term dataset of SNA (p = 0.035). Conclusion: Clozapine treatment in PDP patients may carry a very low risk of SNA and a low risk of MMN.