COVID-19: Risks, Complications, and Monitoring in Patients on Clozapine

Abstract

The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection for patients on clozapine and we give advice on measures to be taken, especially in regard to the monitoring of clozapine plasma levels, WBC count and differentiation during COVID-19 and after vaccination. We present an overview of relevant editorials, observational studies, and case studies, in which COVID-19 was reported in patients on clozapine. Patients using clozapine may have a higher risk of infection than patients with schizophrenia spectrum disorders (SSD) using other antipsychotics. SARS-CoV-2 infection can result in a dangerous increase of clozapine plasma levels, and granulocytopenia and lymphocytopenia (generally mild and short-term) may also occur, usually not as a result of clozapine treatment. Clozapine intoxication, pneumonia and delirium are the main complications of COVID-19 in patients on clozapine. In order to prevent clozapine intoxication, reduction of the original dose by half is generally recommended in clozapine users who contract COVID-19. When a cytokine storm is suspected in an advanced stage of COVID-19, reduction by three quarters seems more appropriate. If COVID-19 patients on clozapine develop granulocytopenia, SARS-CoV-2, rather than clozapine, should be considered as the cause. Schizophrenia patients in general and clozapine users in particular belong to a high-risk group that warrants early vaccination on a medical indication.

Clozapine and COVID‐19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study

“… 18 In our systematic review, we found that a dangerous increase in clozapine blood levels is a common complication in critically ill COVID‐19 patients. 19 We also found that lymphocytopenia and granulocytopenia are generally mild and transient and a result of COVID‐19 rather than of clozapine treatment. Other complications of COVID‐19 associated with clozapine are delirium and COVID‐19 pneumonia.…”

“…When after immunization a mild or moderate granulocytopenia is found—in contradiction with the European Medicines Evaluation Agency (EMEA) text—ongoing clozapine treatment with extra monitoring of WBC and granulocytes should be considered in long‐term recipients of clozapine. 19 A transient, not clinically significant, decline in lymphocytes and neutrophils is, after all, most likely caused by the vaccine.…”

“…While the possible protective or unprotective properties of clozapine remain unclear, clozapine use and SARS‐CoV‐2 infection can lead to complications, since clozapine blood levels rise due to inflammatory responses with cytokines such as IL‐6 and IL‐1, which inhibit the cytochrome P450 enzyme CYP1A2 18 . In our systematic review, we found that a dangerous increase in clozapine blood levels is a common complication in critically ill COVID‐19 patients 19 …”

Haematological changes and adverse events associated with BNT162b2 mRNA COVID‐19 vaccine in patients receiving clozapine—Findings from an audit

“…1 COVID-19 vaccination has been recommended for persons with SMI, including those on clozapine therapy. [1][2][3] SARS-CoV-2 infection can result in elevated clozapine levels and toxicity in clozapine users but limited information is available on risk of COVID-19 vaccinations in clozapine users. 2 Thompson et al reported a case of elevated clozapine levels presenting with delirium, increased falls and incontinence 4 days after receiving a dose of the BNT162b2 mRNA vaccine.…”

“…[1][2][3] SARS-CoV-2 infection can result in elevated clozapine levels and toxicity in clozapine users but limited information is available on risk of COVID-19 vaccinations in clozapine users. 2 Thompson et al reported a case of elevated clozapine levels presenting with delirium, increased falls and incontinence 4 days after receiving a dose of the BNT162b2 mRNA vaccine. 4 Others have postulated that elevated clozapine levels and toxicity may be related to the inhibition of CYP1A2 enzyme during inflammation.…”