The Safety of 12-Weekly Monitoring of Neutrophil Count in Long-Term Clozapine Patients

Clozapine is the only truly effective treatment for refractory schizophrenia, but its use is constrained by the requirements for frequent monitoring of neutrophil counts. In the UK during the COVID-19 pandemic, the frequency of clozapine blood monitoring was reduced in some units from 4-weekly to 12-weekly. We aimed to investigate the outcomes of reduced monitoring in long-term clozapine patients.

This was an anonymous, retrospective, observational cohort study. No restrictions were applied regarding care setting (i.e., outpatients or inpatients). All patients who registered for reduced frequency haematological monitoring from 1 March 2020 to 1 November 2022 were included and followed up till 1 August 2024. The primary outcome was death resulting from clozapine-induced agranulocytosis (CIA). Secondary outcomes were the proportion of patients with mild to moderate neutropenia during the follow-up period and the proportion of patients who reverted to standard monitoring during the study period.

Amongst 1025 patients, there were no cases of agranulocytosis over 3365.9 patient-years of 12-weekly blood monitoring (incident rate 0.0 per 100 person-years). There were 43 episodes of mild neutropenia (so-called amber results-1.5-2.0 × 10⁹/L) or neutropenia (red results < 1.5 × 10⁹/L), an overall incident rate of 1.28 per 100 person-years. During follow-up, 41 patients (4%) reverted permanently to standard 4-weekly monitoring, and 157 patients (15%) temporarily interrupted reduced frequency monitoring but restarted 12-weekly monitoring before the end of the follow-up period. In total, 42 patients (4%) died during the observation period-no death was related to agranulocytosis.

Reducing the frequency of clozapine haematological monitoring to 12-weekly was safe in a group of long-term patients. No cases of agranulocytosis occurred and no deaths due to agranulocytosis were recorded. Most patients remained on extended-interval monitoring.