Antipsychotic Use Increases Risk for Severe COVID-19 Infection Outcomes

Results of a nationwide population-based study published in The Lancet Psychiatry demonstrate a significant relationship between exposure to antipsychotics and COVID-19 infection, in which antipsychotic use increased risk for severe respiratory infection outcomes.

Severe mental disorders have been associated with an increased risk for respiratory infections and COVID-19-related hospitalization and mortality. However, it remains unclear whether antipsychotic drugs contribute to this increased risk – especially during the COVID-19 pandemic.

To this aim, investigators used data from nationwide registers in Denmark to evaluate respiratory infection risk associated with exposure to antipsychotic therapies. Adults (N=85,083) living in Denmark between January and March 2020 with schizophrenia spectrum disorders were evaluated for respiratory infection outcomes between March 2020 and December 2021 on the basis of prevalent antipsychotic use, incident antipsychotic use, and antipsychotic nonuse. The investigators defined mild infection as a positive COVID-19 test or receipt of an anti-infective prescription and severe infection as hospitalization or death from a respiratory infection.

A total of 85,083 people were included in the analysis. The individuals had a median (interquartile range [IQR]) age of 45.8 (IQR, 31.1-60.2) years and 52.1% were women. In the 5 years before the index date, 30,984 individuals were using antipsychotics (eg, prevalent use) and 54.099 were not (eg, unexposed controls). Among the unexposed cohort, 2660 started using antipsychotics after the index date (eg, incident use) and 43,436 did not (eg, unexposed controls).

Prevalent antipsychotic use was associated with increased risk for COVID-19 hospitalization (hazard ratio [HR], 1.28; 95% CI, 1.07-1.52), hospitalization with non-COVID-19 respiratory infection (HR, 1.61; 95% CI, 1.44-1.79), and non-COVID-19 respiratory infection-related mortality (HR, 1.61; 95% CI, 1.18-2.21) compared with unexposed controls.

Incident antipsychotic use was associated with higher risk for hospitalization with COVID-19 (HR, 2.90; 95% CI, 1.66-5.08) or non-COVID-19 respiratory infection (HR, 2.10; 95% CI, 1.28-3.47) compared with unexposed controls.

When stratified by antipsychotic type, the prevalent use of olanzapine (HR, 1.51) and aripiprazole (HR, 1.40) was associated with a higher risk for COVID-19 hospitalization. Prevalent use of clozapine (HR, 1.61), zuclopenthixol (HR, 1.54), quetiapine (HR, 1.52), and olanzapine (HR, 1.47) was associated with higher risk for non-COVID-19 respiratory infection hospitalization. Additionally, prevalent use of zuclopenthixol (HR, 2.15) and olanzapine (HR, 1.51) was associated with non-COVID-19 respiratory infection-related mortality compared with nonuse.

Incident use of risperidone (HR, 7.38) and olanzapine (HR, 3.70) significantly increased COVID-19 hospitalization risk and incident olanzapine was associated with non-COVID-19 respiratory infection hospitalization risk (HR, 3.10), compared with nonuse. Further, incident olanzapine use was associated with increased risk for receipt of anti-infective agents (HR, 1.51) whereas incident aripiprazole use was associated with decreased risk (HR, 0.64) compared with controls.

In general, the association between antipsychotics and COVID-19 hospitalization risk tended to increase with age, becoming significant among individuals aged 70 years or older. For non-COVID-19 respiratory infection hospitalizations, the relationship became significant among individuals aged 40 years or older.

Study authors concluded, “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group,” the investigators concluded. “[I]t seems reasonable to consider recommending pneumococcal (and potentially other anti-infective) vaccination for individuals with a schizophrenia spectrum disorder, who are older than 40 years, and are treated or due to commence treatment with antipsychotic medication.”

This study was limited by not including the severity of schizophrenia.

This article originally appeared on Psychiatry Advisor