Antipsychotic use tied to severe infection risk in patients with schizophrenia

Key takeaways:

• Patients with schizophrenia had greater risk for severe respiratory infections while on antipsychotics.
• Patients aged 70 to 79 years showed increased risk.
• Clozapine was not associated with excessive risk.

Adults with a schizophrenia spectrum disorder had increased risk for severe infection outcomes while exposed to antipsychotics compared with nonexposure periods, according to a study published in The Lancet Psychiatry.

“We do not suggest the avoidance of specific antipsychotics but rather adherence to treatment guidelines and a call for increased vigilance regarding this at-risk group,” Vardan Nersesjan, MD, a PhD student in the faculty of health and medical sciences at University of Copenhagen in Denmark, and colleagues wrote.

Although previous studies during the COVID-19 pandemic confirmed that infection risk and mortality are increased among patients with schizophrenia, it had not been established whether antipsychotic medication imposes additional risk, the researchers wrote.

This prompted Nersesjan and colleagues to perform a register-based cohort study to investigate the risk for mild or severe COVID-19 and non-COVID-19 respiratory infection outcomes among patients taking antipsychotic medication.

They used several nationwide Danish registers, including National Prescription Registry, National Hospital Registry, Psychiatric Research Register and others to identify 85,083 residents of Denmark aged 18 years and older (52.1% men; median age, 45.8 years) with a schizophrenia spectrum disorder. Of this cohort, 30,984 were exposed to antipsychotics during the study period.

Researchers observed the participants from March 1, 2020, through 2021 to identify mild infection outcomes — defined as positive SARS-CoV-2 polymerase chain reaction (PCR) and anti-infective drug prescriptions — and severe infection outcomes, which included hospitalization and death.

After adjusting for demographic and socioeconomic factors and comorbidity, Nersesjan and colleagues found that prevalent users of antipsychotics had a lower risk for a positive SARS-CoV-2 PCR (HR = 0.91; 95% CI, 0.85-0.97), with no difference regarding the risk for redeeming an anti-infective drug (HR = 1.01; 95% CI, 0.97-1.06), during exposure vs. nonexposure periods.

Concerning severe infection outcomes, hospitalization risk for COVID-19 (HR = 1.28; 95% CI, 1.07-1.52) and non-COVID-19 respiratory infection (HR = 1.61; 95% CI, 1.44-1.79) both increased among prevalent users during exposure periods.

Although risk for COVID-19 mortality did not significantly increase during exposure periods among prevalent users (HR = 1.24; 95% CI, 0.82-1.86), risk for mortality related to non-COVID-19 respiratory infections was significantly greater (HR = 1.61; 95% CI, 1.18-2.21).

Focusing on age groups of prevalent users, Nersesjan and colleagues found that COVID-19 hospitalization risk significantly increased among patients aged 70 to 79 years (HR = 1.68; 95% CI, 1.18-2.41) and 80 years or older (HR = 1.64; 96% CI, 1.04-2.57) in exposure vs. nonexposure periods.

Non-COVID-19 hospitalization risk increased among individuals aged older than 40 years, with the greatest risk seen among those aged 70 to 79 years (HR = 2; 95% CI, 1.62-2.46). Mortality risk appeared greater among those aged 50 to 59 years (HR = 3.53; 95% CI, 1.22-10.22) and 70 to 79 years (HR = 2.19; 95% CI, 1.31-3.67).

Finally, researchers observed similar outcomes for all analyses when looking at individual antipsychotics, including no excess risk with clozapine exposure, which had been a concern during the COVID-19 pandemic due to the drug’s impact on the immune system, according to the researchers.

Nersesjan and colleagues noted several limitations to this study, including a lack of race and ethnicity data and lower number of events related to the mortality outcomes.

“Based on our findings and in corroboration with previous findings, it 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,” Nersesjan and colleagues wrote.