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.