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Antipsychotic Use May Decrease Risk of COVID-19 in Patients With BD and SMI
A retrospective cohort study published online in JAMA Network Open found that the use of second-generation antipsychotic medications was associated with a decreased risk of COVID-19 infection in patients with bipolar disorder and other serious mental health disorders.
Here, researcher Katlyn Nemani, MD, of the New York University School of Medicine, discusses the study’s design, significant findings, and surprising outcomes including the increased risk of infection observed in association with valproic acid use.
In the upcoming part 2, Dr Nemani explains the study’s clinical implications and further research needed in this area.
In a previous Q&A, Dr Nemani discusses her study that found a schizophrenia spectrum diagnosis was associated with increased mortality risk in patients with COVID-19.
Question: What led you and your colleagues to investigate association between the use of psychotropic medications and the risk of COVID-19 infection among long-term inpatients with serious mental illness?
Answer: Prior to this study, we found that a diagnosis of a schizophrenia spectrum disorder is associated with a near 3-fold increase in mortality risk in the setting of Covid-19 infection. This finding was replicated by several groups, prompting the CDC to add schizophrenia to its list of conditions associated with high risk of severe infection.
In a subsequent study of adults with serious mental illness (SMI) diagnosed with Covid-19, we found no difference in mortality in patients prescribed antipsychotic medication compared to those who were not, suggesting that antipsychotic treatment is unlikely to account for increased mortality risk.
However, individual medications may differ in their associations with infection and adverse outcomes. There have been concerns that some medications, such as clozapine, may contribute to increased infection risk. We were interested in exploring this in long-term inpatients with SMI given their high risk of viral exposure and uniform access to testing and treatment, allowing us to better assess the potential effects of medications.
Q. Please briefly describe the study method and the participants included in the study.
A. This was an observational study of adults with SMI (schizophrenia, schizoaffective disorder, and bipolar disorder) residing in psychiatric hospitals operated by the New York State (NYS) Office of Mental Health (OMH) between March 8, 2020 and July 1, 2020. A total of 1958 patients received testing for Covid-19 during this period and were included in the study.
The exposures of interest were psychotropic medications prescribed prior to Covid-19 testing. The primary outcome was Covid-19 infection, defined by a positive PCR or antibody test result. The secondary outcome was Covid-19-related death among patients with laboratory-confirmed infection.
Q: Please briefly describe the most significant finding(s).
A total of 969/1958 patients (50%) had laboratory confirmed Covid-19 infection that occurred while hospitalized; of those, 38 (4%) died. We found decreased odds of infection among patients prescribed second-generation antipsychotics including paliperidone, risperidone, and quetiapine.
In contrast, we found increased infection associated with use of valproic acid. We saw similar findings in the mortality analysis, though these associations were not statistically significant (likely due to insufficient sample size). Clozapine use was associated with reduced mortality among patients with confirmed infection.
A. Were any outcomes different than you expected?
The protective effect we saw in association with second generation antipsychotics was somewhat surprising. In vitro evidence prior to this study suggested that first-generation antipsychotics, but not second-generation antipsychotics, interfere with viral replication through interactions with the sigma-1 receptor. Further investigation is needed to determine whether the protective effect of second-generation antipsychotics might be mediated through another antiviral mechanism or by modulating the host immune response. The protective effect of clozapine in the setting of infection is of particular interest given its unique mechanism of action.
The increased risk of infection observed in association with valproic acid use was unexpected. There are several potential explanations that may underlie this finding, including downregulation of ACE-2 receptors and other molecular mechanisms that may contribute to impaired immune function. However, further research is needed to replicate this finding and determine whether this association might be mediated other factors such as underlying psychopathology.
Reference
Dr Katlyn Nemani is a clinical research psychiatrist at the Nathan Kline Institute and Research Assistant Professor of Psychiatry at the New York University School of Medicine. After earning her medical degree at Tufts University, Medford, Massachusetts, she completed combined residency training in neurology and psychiatry at NYU. Her research is focused on understanding the bidirectional relationship between systemic disease and psychopathology, particularly the interaction between the nervous system and immune system in people with psychosis.
