A case report: Clozapine‐induced leukopenia and neutropenia after mRNA COVID‐19 vaccination

Abstract Clozapine is an atypical antipsychotic used for treatment‐resistant schizophrenia and is known to cause serious side effects, such as leukopenia and neutropenia. We encountered the case of a 44‐year‐old female patient with a good response to clozapine, who experienced inflammatory reaction and cytopenia after coronavirus disease 2019 (COVID‐19) vaccination. Soon after clozapine discontinuation, the inflammatory reaction resolved, and cell counts recovered. There are only a few reports on the interaction between clozapine and COVID‐19 vaccine. Our findings suggest that caution is required when a patient who is receiving clozapine scheduled for COVID‐19 vaccination, owing to the possibility of cytopenia. Moreover, blood tests and the measurement of clozapine concentration should be performed before and after the inoculation to ensure patient safety.


| C A SE
The patient was a 44-year-old Japanese woman with symptoms of schizophrenia, particularly hallucination and avolition. Almost all atypical antipsychotics, such as olanzapine (15 mg), brexpiprazole (2 mg), and lurasidone (80 mg), were ineffective in combating the symptoms or were poorly tolerated; therefore, the dosages of these drugs were reduced, and they were discontinued before starting clozapine.
After blood testing (day 0), treatment with 12.5 mg clozapine tablets, which were taken orally after every evening meal, was started (day 1). A week later (day 7), the patient's white blood cell (WBC) count had decreased from 4790 to 4030/μL, and the neutrophil count had decreased from 2012 to 1572/μL. On the same day, lithium carbonate (200 mg), adenine (60 mg), and mecobalamin (1500 μg) were added to her drug regimen to increase her WBC count. As expected, her WBC count normalized a few days later.
After the clozapine dose was increased to 50 mg (

C A S E R E P O R T A case report: Clozapine-induced leukopenia and neutropenia after mRNA COVID-19 vaccination Abstract
Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia and is known to cause serious side effects, such as leukopenia and neutropenia. We encountered the case of a 44-year-old female patient with a good response to clozapine, who experienced inflammatory reaction and cytopenia after coronavirus disease 2019 (COVID-19) vaccination. Soon after clozapine discontinuation, the inflammatory reaction resolved, and cell counts recovered. There are only a few reports on the interaction between clozapine and COVID-19 vaccine. Our findings suggest that caution is required when a patient who is receiving clozapine scheduled for COVID-19 vaccination, owing to the possibility of cytopenia. Moreover, blood tests and the measurement of clozapine concentration should be performed before and after the inoculation to ensure patient safety.

K E Y W O R D S
clozapine, COVID-19 vaccine, leukopenia, neutropenia, schizophrenia neutrophil counts further decreased. On the following day, her WBC and neutrophil counts were 3000 and 1029/μL, respectively. A decision was made to stop the clozapine. Soon after the discontinuation of clozapine, her WBC count and the ratio of neutrophils to other leukocytes normalized.
The other side effects of clozapine, such as slight drowsiness and hypersalivation, also subsided. The patient did not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and her glucose tolerance and blood glucose level were unaffected throughout the process. We were unable to measure her blood concentration of clozapine in our facility.

| DISCUSS ION
In this case, there are three possibilities for the cytopenia. First, the inflammatory reaction caused by COVID-19 vaccination probably inhibited cytochrome P450 1A2 activity, suppressing clozapine metabolism and elevating the blood level of the medication. 1    In conclusion, psychiatrists should be aware of the risk of side effects, including cytopenia, when patients who are receiving treatment with clozapine are to be vaccinated. Therefore, blood cell count, and if possible, plasma concentration of clozapine should be measured before and after the inoculation for close monitoring.

ACK N OWLED G M ENTS
We would like to thank the patient for allowing the publication of this report and Editage (www.edita ge.com) for English language editing.

CO N FLI C T O F I NTE R E S T
The authors have no conflicts of interest to declare.

AUTH O R CO NTR I B UTI O N S
All authors contributed to the writing of the paper and approved the final manuscript.

I N FO R M E D CO N S E NT
Informed consent from the patient was acquired at the time of the publication of this report.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable for this article as no datasets were generated or analyzed during the current study.