Antipsychotic use and psychiatric disorders in COVID-19.

Huazhen Yang and colleagues’ study, published in The Lancet Healthy Longevity, which examined the association between psychiatric disorders and clinical outcomes of COVID-19, is timely, novel, and potentially carries broad implications. The study's main finding was that patients with prepandemic-confirmed psychiatric illness had increased odds of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (adjusted odds ratio 1·44, 95% CI 1·28–1·62), hospitalisation (1·55, 1·34–1·78), and COVID-19-related death (2·03, 1·59–2·59).

Although we acknowledge the perils of disentangling causal pathways (ie, the estimation of total causal effects requires less stringent assumptions than the identification of direct and indirect effects), further understanding of the mechanisms underlying the association between psychiatric illness and COVID-19 remains warranted. As such, in addition to the potential mechanisms pointed out by the authors (eg, immune response, impairment mediated by the endocrine axis, and cytokine production dysregulation), the use of antipsychotic medications requires attention.

People who use antipsychotics are at increased risk of infection, including community-acquired pneumonia, urinary tract infections, and bloodstream infections. Because patients in Yang and colleagues’ study were mainly diagnosed with depression, substance misuse, and anxiety—conditions that are increasingly treated with antipsychotic agents—we believe that such risk might partly explain the observed association between psychiatric illness, COVID-19, and its severity. The findings of strong associations between psychotic disorders and risk of poor outcomes of COVID-19 might point to antipsychotics as potential culprits.

Thus, we believe the study by Yang and colleagues emphasises a clear need for further research evaluating the association between psychiatric disorders, antipsychotic use, the dysregulation of the immune response, and the occurrence of life-threatening infections. Future studies should assess the role of antipsychotic treatment in infection, to shed light on the underlying mechanisms of the effect of psychiatric disorders on SARS-CoV-2 infection. Comparison between different antipsychotic medications would be of special relevance given that the risk does not appear to be uniform across agents—ie, both clozapine and pure dopaminergic agents might carry a higher infection risk.4, 5