Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report

Abstract

Background: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19.

Patients & methods: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin.

Results: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 ​× ​10⁹/l (SD ​= ​2.70) which constituted a significant drop from a baseline value of 5.2 ​× ​10⁹/l (SD ​= ​2.24). The mean relative reduction in ANC was -0.2729 (SD ​= ​0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue ​= ​8.96 ​× ​10^-8 and an adjusted R² of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline.

Conclusions: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

Keywords: Absolute Neutrophil Count (ANC); Agranulocytosis; COVID-19; Clozapine; Coronavirus; Lymphopenia; Neutropenia; Neutrophilia; Neutrophils; Psychosis; SARS-CoV-2; Schizophrenia.

Fig. 1

Absolute Neutrophils Count (ANC) and White Cell Count (WCC) pre-, during, and after SARS-CoV-2 infection in patients taking clozapine. Baseline is an average of ANC and WCC values of previous 3 years.