Do Psychotropic Meds Raise or Lower COVID Risk?

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Different psychotropic medications are associated with different risks of COVID-19 in hospitalized patients with serious mental illness, a new study suggests.

Investigators found that second-generation antipsychotics were associated with a 48% lower risk of COVID-19, while valproic acid was associated with a 39% increased risk of the disease

“Exposures to several psychotropic medications were associated with risk of COVID-19 infection among inpatients with serious mental illness; decreased risk was observed with the use of second generation antipsychotics, with paliperidone use associated with the largest effect size. Valproic acid use was associated with an increased risk of infection,” the investigators, led by Katlyn Nemani, MD, at NYU Langone Medical Center, New York, write.

The study was published online May 6 in JAMA Network Open.

Vulnerable Population

Patients with serious mental illness are particularly vulnerable to COVID-19. Psychotropic medications have been identified as potential therapeutic agents to prevent or treat several COVID-19, but they have not been systematically studied in this patient population.

The researchers analyzed data from 1958 adults who were continuously hospitalized with serious mental illness from March 8 to July 1, 2020. The mean age was 51.4 years, and 1442 (74%) were men.

A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 while hospitalized, and 38 (3.9%) died ― a mortality rate four times higher than estimates from the general population in New York during the same time frame, the researchers note.

“This finding is consistent with prior studies that have found increased rates of infection in congregate settings and mortality after among patients with serious mental illness,” the investigators increased write.

The use of second-generation antipsychotic medications, as a class, was associated with a lower likelihood of COVID-19 (odds ratio [OR], 0.62; 95% CI, 0.45 – 0.86), while the use of mood stabilizers was associated with increased likelihood of infection (OR, 1.23; 95% CI, 1.03 – 1.47).

In a multivariable model of individual medications, use of the long-acting atypical antipsychotic paliperidone was associated with a lower odds of (OR, 0.59; 95% CI, 0.41 – 0.84), and use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10 – 1.76).

Valproic acid downregulates angiotensin-converting enzyme 2 in endothelial cells, which may impair immune function and contribute to poor outcomes for patients with COVID-19, the researchers say.

The use of clozapine was associated with reduced odds of COVID-related death (unadjusted OR, 0.25; 95% CI, 0.10 – 0.62; fully adjusted OR, 0.43; 95% CI, 0.17 – 1.12).

“Although there have been concerns about clozapine use during the pandemic as a risk factor for acute and potential toxic effects during infection, clozapine increased use was not associated with an risk of COVID-19 infection or death in the present study. In fact, unadjusted estimates suggested a significant protective association,” the investigators write.

However, they note, data on clozapine and COVID-19 have been mixed.

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