Antipsychotics Protective Against COVID-19?

Megan Brooks

April 15, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Antipsychotics may protect against SARS-CoV-2 infection or lead to a milder course of illness, new research suggests.

"Counterintuitively," the investigators note, vulnerable people with severe mental illness "on antipsychotic treatment showed a lower risk of SARS-CoV-2 infection and a likely better COVID-19 prognosis."

"These are very interesting findings that reflect a clinical reality where we see few patients with severe COVID-19, despite the presence of various risk factors," study investigator Manuel Canal-Rivero, PhD, clinical psychologist, Virgen del Rocio University Hospital, Sevilla, Spain, said in a news release.

"The number of COVID-19 patients is lower than expected among this group of people and in cases where a proven infection does occur, the evolution is benign and does not reach a life-threatening clinical situation. These data as a whole seem to point to the protective effect of the medication," Canal-Rivero added.

The study was published online as a letter to the editor February 19 in Schizophrenia Research.

A "Striking" Finding

The researchers assessed the prevalence and prognosis of COVID-19 in 698 patients with serious mental disorders (SMDs) receiving treatment with long-acting injectable antipsychotic medication. The non-SMD population included the catchment area population of 557,576 individuals.

From February to November 2020, 4.1% of the non-SMD population were infected with SARS-CoV-2 vs just 1.3% of the SMD population (9 of 698 patients). All but one patient with SMD had asymptomatic illness (8 of 9, 89%). Accurate information on asymptomatic illness in the non-SMD population was not available.

There were also fewer hospital admissions in the SMD population (0% vs 8.5%), ICU admissions (0% vs 0.9%) and deaths because of COVID-19 (0% vs 1.1%), although the differences were not statistically significant.

In related research, the same investigators found that many of the genes whose expression is altered by SARS-CoV-2 infection are significantly down-regulated by antipsychotic drugs.

"In a striking way, we have shown how antipsychotics reduce the activation of genes involved in many of the inflammatory and immunological pathways associated with the severity of COVID-19 infection," Benedicto Crespo-Facorro, MD, PhD, University of Sevilla, who led the study, said in the news release.

"Although this finding requires replication, the discovery could be very significant because the treatment of COVID-19 with drugs originally indicated for unrelated clinical situations, that is to say drug repositioning, has been shown to be an interesting source of effective treatments for COVID-19 patients," he added.

Antiviral Properties?

Reached for comment, Samoon Ahmad, MD, professor, Department of Psychiatry, NYU Grossman School of Medicine in New York City, said the findings are "fascinating" and should be explored further.

While the findings on long-acting injectable antipsychotic treatment "seem counterintuitive at first, they are in line with other studies," said Ahmad, who heads the inpatient psychiatry unit at Bellevue Hospital Center and is founder of the Integrative Center for Wellness in New York City.

"We know that certain antipsychotics can suppress the expression of inflammatory cytokines (thereby theoretically preventing cytokine storm) and antidepressant medications appear to activate key cellular proteins that the SARS-CoV-2 virus uses for replication," explained Ahmad, who was not associated with the study.

For example, as reported by Medscape Medical News, a preliminary study published last year showed that early treatment with the antidepressant fluvoxamine prevented clinical deterioration in adult outpatients with confirmed COVID-19.

The antipsychotic aripiprazole has also shown potential to treat severe COVID-19 infection.

"Consequently, there appears to be a possible explanation as to why these drugs afford patients with severe mental disorders increased protection against the SARS-CoV-2 virus," Ahmad told Medscape Medical News.

However, he cautioned, there are several factors at play that could influence the results. Therefore, more research is needed before drawing any firm conclusions.

"Still, the possibility that psychiatric medications may have antiviral properties is a tremendous development and I really hope that additional studies confirm the preliminary findings," Ahmad said.

The study had no specific funding. The authors and Ahmad have disclosed no relevant financial relationships.

Schizophrenia Res. Published online February 19, 2021. Letter to the Editor

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