Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study

Abstract

Background: To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.

Aims: To investigate the impact of this temporary policy change on clinical and safety outcomes.

Method: All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.

Results: Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.

Conclusions: There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

Keywords: COVID-19; Clozapine; agranulocytosis; neutropenia; pharmacovigilance.

Fig. 1

Summary of the UK Medicines & Healthcare products Regulatory Agency (MHRA) guidelines for clozapine monitoring frequency (white cell count and absolute neutrophil count) and the emergency 12-weekly monitoring protocol.

Fig. 2

The mirror-image design. SLaM, South London and Maudsley NHS Foundation Trust; ELFT, East London NHS Foundation Trust.