Schizophr Res. 2026 Aug 3;297:76-88. doi: 10.1016/j.schres.2026.07.026. Online ahead of print.
ABSTRACT
BACKGROUND: Concerns about haematological toxicity and absolute neutrophil count (ANC) monitoring may limit clozapine use, particularly in multi-ethnic populations where benign ethnic neutropenia (BEN) and lower baseline ANC are common. We characterised baseline ANC distribution, nationality-derived BEN-risk, post-initiation ANC outcomes, and haematological monitoring patterns in a multi-ethnic United Arab Emirates clozapine cohort.
METHODS: We conducted a retrospective cohort study at a tertiary psychiatric hospital in the United Arab Emirates. Adults with documented clozapine administration and at least one post-initiation ANC between 1 January 2018 and 31 July 2024 were included. Nationality-derived BEN-risk, baseline ANC, post-initiation ANC outcomes within a five-band hierarchy, monitoring intensity, and pre-specified sensitivity and exploratory analyses were examined.
RESULTS: Among 239 patients, 179 formed the final study cohort, contributing 284.7 on-clozapine person-years. Overall, 158 patients (88.3%) had no post-initiation ANC <2.0 × 109/L, 16 (8.9%) entered the 1.5-2.0 × 109/L low-ANC monitoring range, 2 (1.1%) reached conventional-threshold neutropenia, 3 (1.7%) reached severe neutropenia, and none reached agranulocytosis range. Five patients (2.8%) met the clinically meaningful ANC <1.5 × 109/L threshold; all were BEN-risk, all had concomitant valproate exposure, and four had concomitant lithium exposure. Baseline ANC was lower in BEN-risk patients and statistically accounted for much of the BEN-risk-to-outcome association in an exploratory analysis.
CONCLUSIONS: Low ANC during clozapine treatment was uncommon and strongly shaped by baseline ANC and BEN-risk context. Baseline ANC-informed and BEN-aware interpretation may reduce unnecessary treatment interruption while preserving haematological safety. BEN-risk was inferred from nationality, not confirmed genetically; all five low-ANC cases received concomitant valproate; associations are observational.
PMID:42546354 | DOI:10.1016/j.schres.2026.07.026
