Clozapine treatment and risk of COVID-19 infection: retrospective cohort study

Abstract

Background Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia. Aims To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK. Method Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use. Results Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73–3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14–2.72). Conclusions These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

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

“…Adverse reactions to clozapine include neutropenia (2.7% of patients) which can prefigure an impending life-threatening agranulocytosis, (0.4% of patients) ( Atkin et al, 1996 ; Gee and Taylor , 2020; Pandarakalam, 2020 ). Clozapine treatment is also associated with diabetes, obesity, pulmonary disease ( Gee et al, 2020 ; Dragoi et al, 2020 ) and a reported increased risk of COVID-19 infection ( Govind et al, 2020 ). Switching to an alternative antipsychotic in patients clinically stable on clozapine is challenging, both for clinicians and patients, as this strategy is associated with a high risk of relapse due to the high likelihood of patients who have required treatment with clozapine being resistant to treatment with other antipsychotics ( Butler et al, 2020 ; Chiappini et al, 2020 ).…”

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

“…Psychiatrists and healthcare providers involved in monitoring the absolute neutrophil count (ANC) and dispensing the prescription must be aware of the increased risks in clozapine-treated patients with COVID-19. They must communicate and strengthen the monitoring of side effects, including their duration, as the full impact of the COVID-19 pandemic is still unknown [ 106 ].…”

Toxicity of psychotropic drugs in patients with COVID-19: A systematic review

“…However, the causal role of clozapine and comedication with quetiapine in this case is uncertain. One study suggested an increased risk for SARS-CoV-2 infection [ 11 ] in patients treated with clozapine but does not report the risk for COVID-19 pneumonia. Earlier studies conducted before the SARS-CoV-2 pandemic have suggested an increased risk for pneumonia, probably more concerning bacterial pneumonia [ 21 , 30 ].…”

“…Despite initial concerns, patients with preexisting psychiatric disorders do not seem to be at higher risk of SARS-CoV-2 infection [ 10 ]. One retrospective study suggested that patients treated with clozapine may be at higher risk than patients treated with other antipsychotics, but these results need replication [ 11 ]. Overall, given the extremely widespread population, there are numerous patients with ongoing psychiatric treatment who develop COVID-19 [ 12 ].…”