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Does clozapine directly increase the risk of severe COVID-19 symptoms? After all, clozapine increases the risk of pneumonia. Well, the answer is as you might suspect, [is] yes; receiving clozapine increases the person’s risk of COVID-19 infection. However, the interesting part here is clozapine’s effects on immune vulnerability.
In this Quick Take, we will look at an article in The British Journal of Psychiatry by Risha Govind and colleagues from King’s College in London. First, the result, yes, relative to other antipsychotics, clozapine was associated with a doubling, almost a tripling of some kinds of risk for COVID-19 infection. However, the authors adjusted for attributes that go along with getting clozapine that might account for some of this increased risk without blaming the clozapine itself. That takes us into interesting territory. What increases the risk of COVID-19 infection in people taking clozapine?
Well, let’s take the simple ones first. Smoking and increased body mass index (BMI). People who take clozapine smoke more cigarettes than people taking other antipsychotics. Of course, clozapine can cause more weight gain relative to other antipsychotics. That is associated with an increased risk of diabetes.
Moreover, diabetes is a risk factor for severe forms of COVID infection, which increases the rate of coming to medical attention and getting logged as having it. Also, the authors point out that perhaps hypersalivation increases the risk of pneumonia. Thus, having more severe schizophrenia and getting clozapine is a risk for getting hospitalized, which ironically increases the risk of COVID-19 through close exposure. Even the regular clinic visits needed with clozapine contribute to that risk.
However, on top of all these, there are direct immunologic effects of clozapine. Of course, there is neutropenia early in treatment, but the authors note evidence that clozapine also reduces all 3 classes of circulating immunoglobulins (IgM, IgA, and IgG) compared with other antipsychotics.
That is quite a list of reasons why people taking clozapine are at risk of COVID-19 infection and severe experiences when they get it. Hopefully, you and your teams are already taking multiple precautions to protect these patients and yourselves. In summary, if there are any additional steps you can take, it is the people taking clozapine who particularly need them.
Abstract
Clozapine Treatment and Risk of COVID-19
Risha Govind, Daniela Fonseca de Freitas, Megan Pritchard, Richard D. Hayes, James H. MacCabe
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 in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications, using electronic health records data, in a geographically defined population in London.
Method: Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6,309 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, BMI, smoking status, and SLAM service use.
Results: Of 6,309 patients, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 compared with those who were on other antipsychotic medication (unadjusted HR = 2.62 (95% CI 1.73 – 3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted hazard ratio 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. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.
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Reference
Govind, R., de Freitas, D. F., Pritchard, M., Hayes, R. D., & MacCabe, J. H. (2020). Clozapine treatment and risk of COVID-19. The British Journal of Psychiatry, 1-13.
