Abstract

There is both uncertainty regarding the safety of clozapine in COVID-19 patients owing to limited published data and a lack of consensus on continuing clozapine in patients with severe respiratory infections. COVID-19 is known to induce an acute immune response which can affect haematological parameters associated with clozapine monitoring, and systemic infection may reduce clozapine clearance. Clozapine, which has been associated with worse outcomes in some pneumonias, may in theory worsen outcomes in COVID-19. Despite these concerns, there are some data to indicate it is safe to continue clozapine in COVID-19 infection. In this retrospective case series, we describe our experiences of clozapine prescribing and disease progression of eight SARS-CoV-2 positive patients on medical wards in a major London teaching hospital. In four cases clozapine was stopped during the hospital admission. A COVID-19 pneumonia developed in four patients: three of these required intensive care unit admission for an average of 34 days. At the time of writing, three patients had died (two directly from COVID-19 pneumonia), two remained in general hospital wards, two were recovering in the community and one had been transferred to an inpatient psychiatric hospital. Follow-up length varied but in each case was not more than 104 days. Delirium was the most common adverse neuropsychiatric event, and in one case a relapse of psychosis occurred after cessation of clozapine. This retrospective case series illustrates the safe use of clozapine during COVID-19 infection. Our experiences suggest that consideration should be made to continuing clozapine even in those most unwell with COVID-19. We also identify areas which require larger scale hypothesis-testing research.

Highlights

  • SARS-CoV-2 infection, which first emerged in China at the end of 2019, has become a worldwide pandemic

  • Some authors have suggested that the inflammation associated with COVID-19 infection has the potential to precipitate clozapine toxicity,[3,4] and that as clozapine has been associated with increased risk of pneumonia in general, it may increase the risk of pneumonia in patients infected with COVID-19.5 As well as this, data have indicated that the inflammatory cytokines released during infections can inhibit CYP1A2 enzymes, potentially causing clozapine toxicity, with the risk possibly increasing in relation to the severity of inflammation.[6,7]

  • In this retrospective case series, we have presented eight patients who were prescribed clozapine whilst sufficiently unwell with COVID-19 to require treatment in an acute medical hospital, including three who had stays in intensive care due to COVID-19 pneumonia

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Summary

Introduction

SARS-CoV-2 infection, which first emerged in China at the end of 2019, has become a worldwide pandemic. There are currently limited data on the characteristics and outcomes of patients taking clozapine with severe COVID-19 admitted to general hospitals. There have been case reports of successfully continuing clozapine treatment in mildly unwell COVID-19 patients in acute inpatient psychiatric wards.[2] some authors have suggested that the inflammation associated with COVID-19 infection has the potential to precipitate clozapine toxicity,[3,4] and that as clozapine has been associated with increased risk of pneumonia in general, it may increase the risk of pneumonia in patients infected with COVID-19.5 As well as this, data have indicated that the inflammatory cytokines released during infections can inhibit CYP1A2 enzymes, potentially causing clozapine toxicity, with the risk possibly increasing in relation to the severity of inflammation.[6,7] This may be true for COVID-19

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