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Second-generation antipsychotics appeared to curb COVID-19 infection in those with serious mental illness, a retrospective study showed.

Looking at adults hospitalized long-term in the New York psychiatric system in 2020, those taking any agent in the class of second-generation antipsychotic medications, also known as atypical antipsychotics, had a 38% lower chance of infection (OR 0.62, 95% CI 0.45-0.86), reported Donald C. Goff, MD, of the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York, and colleagues in .

After adjusting for age and sex, lower odds of infection were seen in association with use of:

• Clozapine: OR 0.79 (95% CI 0.64-0.98)
• Paliperidone: OR 0.59 (95% CI 0.42-0.81)
• Risperidone (Risperdal): OR 0.67 (95% CI 0.53-0.86)
• Olanzapine (Zyprexa): OR 0.70 (95% CI 0.58-0.86)

After full adjustment for sociodemographic factors, use of paliperidone remained associated with a lower chance of infection (OR 0.59, 95% CI 0.41-0.84).

In an , Benedetta Vai, PhD, of IRCCS San Raffaele Scientific Institute, and Mario Gennaro Mazza, MD, of Università Vita-Salute San Raffaele in Milan, noted that atypical antipsychotics "appear to be a safe and good treatment option" for those with serious mental illnesses.

These findings are particularly encouraging for clozapine, as there have been concerns about this agent acting as a risk factor for pneumonia and having other potential toxic effects during acute infection, Goff and team noted.

"Clozapine is unique among antipsychotics in its ability to enhance the T helper cell type 1 response that supports antiviral immune response and is blunted in schizophrenia," they explained, adding that additional research is needed to determine if clozapine may actually offer protection against severe COVID infection.

However, the study also showed that mood stabilizers were associated with increased odds of COVID infection (OR 1.23, 95% CI 1.03-1.47). Among the moods stabilizers studied -- valproic acid, lithium, and lamotrigine -- valproic acid appeared to drive this increased risk (OR 1.39, 95% CI 1.10-1.76).

As for the first-generation (or "typical") antipsychotics, haloperidol, fluphenazine, and chlorpromazine, only chlorpromazine was associated with decreased infection after adjusting for age and sex (OR 0.59, 95% CI 0.40-0.86).

No agents in any class were linked with COVID-related mortality. However, Goff and colleagues pointed out that this may have been due to an insufficient sample size. COVID-related mortality appeared to be lower among patients on an antidepressant, including sertraline, citalopram, and escitalopram, although this link wasn't statistically significant.

"The potential harms and benefits associated with several psychotropic medications have been explored in preclinical and clinical studies since the start of the COVID-19 pandemic, but, to our knowledge, this is the largest study to systematically assess associations between the use of individual medications and the risk of COVID-19 infection among inpatients with serious mental illness," the authors wrote.

This population is particularly vulnerable, as nearly half of the patients in this cohort contracted laboratory-confirmed COVID -- 969 of 1,958 patients. Furthermore, infection-related mortality was more than four times higher than the general New York population during this same time period, Goff and team highlighted.

They noted that it's important to bear in mind that this study time frame took place during the first pandemic peak in New York, and as such, interventions to curb transmission weren't yet implemented.

The patients included in the analysis were continuous inpatients at 18 New York State Office of Mental Health psychiatric hospitals from March 8 to July 1, 2020. Of the 969 inpatients with confirmed infections, 3.9% died. Mean age was 51.4, and 74% were men.

Among all inpatients, 46.5% had an affective psychotic disorder, including schizoaffective disorder, bipolar I disorder, or major depressive disorder with psychotic features. The rest of the cohort had schizophrenia, delusional disorder, or schizotypal disorder.

Most patients were taking multiple psychotropic medications at the time. Of the total cohort, 61.2% were on a first-generation antipsychotic, 91.6% were on a second-generation antipsychotic, 53.3% were on a mood stabilizer, 51.9% were on benzodiazepines, and 27.9% were on antidepressants.

One limitation to the study was that medication adherence wasn't directly measured, although it was likely high due to the fact that all individuals were inpatients.

Because this study only looked at those in an inpatient setting, commentators Vai and Mazza said future research should focus on patients with serious mental illness in outpatient settings, as these patients may face higher risks since they aren't under close constant medical supervision.

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