Antipsychotics and COVID-19: the debate goes on – Authors' reply
Authors: Livia De Picker, Mario Gennaro Mazza, Benedetta Vai
Journal: The Lancet Psychiatry (2021)

We thank Xavier Boland and Luiz Dratcu for their comments on our meta-analysis.1Vai B Mazza MG Delli Colli C et al.Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis.Lancet Psychiatry. 2021; 8: 797-812Summary Full Text Full Text PDF PubMed Scopus (192) Google Scholar They have accurately identified an essential gap in the current understanding of COVID-19 impact on patients with mental disorders. Most of the available evidence in our meta-analysis relied on electronic health records, which indeed did not allow calculation of the risk associated with antipsychotics without confounding by indication. Nevertheless, risk estimates associated with antipsychotics remained significant in pooled odds ratios for adjusted estimates (2·43 [95% CI 1·81–3·25], I2=61·35%), accounting for age in all three studies and comorbidities in two of the three studies.1Vai B Mazza MG Delli Colli C et al.Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis.Lancet Psychiatry. 2021; 8: 797-812Summary Full Text Full Text PDF PubMed Scopus (192) Google Scholar To differentiate the risks associated with specific drugs and the condition they are meant to treat, we have previously recommended reporting of medication-stratified risk estimates for each psychopharmacological drug class in patients with mental disorders.2De Picker LJ Closing COVID-19 mortality, vaccination, and evidence gaps for those with severe mental illness.Lancet Psychiatry. 2021; 8: 854-855Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar We are glad to see emerging evidence answering our plea. In a recently published study by Nemani and colleagues,3Nemani K Conderino S Marx J Thorpe LE Goff DC Association between antipsychotic use and COVID-19 mortality among people with serious mental illness.JAMA Psychiatry. 2021; (published online Sept 22.)https://doi.org/10.1001/jamapsychiatry.2021.2503Crossref Scopus (22) Google Scholar antipsychotic treatment was not associated with increased mortality among a US cohort of 464 patients with severe mental illness, 196 of whom were treated with antipsychotic medication. However, this does not preclude potential risks associated with specific antipsychotics,4Govind R Fonseca de Freitas D Pritchard M Hayes RD MacCabe JH Clozapine treatment and risk of COVID-19 infection: retrospective cohort study.Br J Psychiatry. 2020; 219: 368-374Crossref Scopus (61) Google Scholar nor does it exclude the possibility of unaccounted-for confounding. Considering current treatment guidelines for severe mental illness, in particular among patients with schizophrenia, an unmedicated status might be an indicator of treatment non-adherence, associated with an increased risk of psychiatric relapse, and a decreased adherence to physical health-care recommendations. In the absence of clear evidence about the detrimental role of antipsychotics, we recommend clinicians to stress the importance and benefit of antipsychotic treatment adherence, while also closely monitoring patients, ensuring timely COVID-19 testing and treatment referral. This ongoing debate proves that an increased understanding of the role of psychiatric treatment modalities on the COVID-19 outcomes of patients with mental disorders, including not only different psychotropic compounds but also psychiatric treatment settings (eg, inpatient vs outpatient care), remains an urgent research priority. LDP reports grants from Boehringer-Ingelheim and Janssen, outside the submitted work. LDP and BV are members of the ECNP ImmunoPsychiatry Network. MGM declares no competing interests. Antipsychotics and COVID-19: the debate goes onIn a meta-analysis on the association of mental illness, its treatment, and COVID-19 risk, Benedetta Vai and colleagues reported a strong association between exposure to antipsychotics and COVID-19 mortality (odds ratio 3·71 [1·74–7·91]).1 This has serious implications for the care of patients with severe mental illness receiving or about to receive antipsychotics during the pandemic. It also raises questions as to whether the use of electronic health records might have limited the scope of the analysis. Full-Text PDF Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysisPre-existing mental disorders, in particular psychotic and mood disorders, and exposure to antipsychotics and anxiolytics were associated with COVID-19 mortality in both crude and adjusted models. Although further research is required to determine the underlying mechanisms, our findings highlight the need for targeted approaches to manage and prevent COVID-19 in at-risk patient groups identified in this study. Full-Text PDF