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Antipsychotics are not responsible for the increased COVID-related death rate among patients with serious mental illness (SMI), new research shows.
The significant increase in COVID-19 mortality that continues to be reported among those with schizophrenia and schizoaffective disorder “underscores the importance of protective interventions for this group, including priority vaccination,” study investigator Katlyn Nemani, MD, research assistant professor, Department of Psychiatry, New York University (NYU) Grossman School of Medicine, New York City, told Medscape Medical News.
The study was published online September 22 in JAMA Psychiatry.
Threefold Increase in Death
Previous research has linked a diagnosis of a schizophrenia spectrum disorder, which includes schizophrenia and schizoaffective disorder, to an almost threefold increase in mortality among patients with COVID-19.
Some population-based research has also reported a link between antipsychotic medication use and increased risk for COVID-related mortality, but these studies did not take psychiatric diagnoses into account.
“This raised the question of whether the increased risk observed in this population is related to underlying psychiatric illness or its treatment,” said Nemani.
The retrospective cohort study included 464 adults (mean age, 53 years) who were diagnosed with COVID-19 between March 3, 2020, and February 17, 2021, and who had previously been diagnosed with schizophrenia spectrum disorder or bipolar disorder. Of these, 42.2% were treated with an antipsychotic medication.
The primary endpoint was death within 60 days of COVID-19 diagnosis. Covariates included sociodemographic characteristics, such as patient-reported race and ethnicity, age, and insurance type, a psychiatric diagnosis, medical comorbidities, and smoking status.
Of the total, 41 patients (8.8%) died. The 60-day fatality rate was 13.7% among patients with a schizophrenia spectrum disorder (n = 182) and 5.7% among patients with bipolar disorder (n = 282).
Antipsychotic treatment was not significantly associated with mortality (odds ratio [OR], 1.00; 95% CI, 0.48 – 2.08; P = .99).
“This suggests that antipsychotic medication is unlikely to be responsible for the increased risk we’ve observed in this population, although this finding needs to be replicated,” said Nemani.
A diagnosis of a schizophrenia spectrum disorder was associated with an almost threefold increased risk for mortality compared with bipolar disorder (OR, 2.88; 95% CI, 1.36 – 6.11; P = .006).
“This was a surprising finding,” said Nemani. “A possible explanation is differences in immune function associated with schizophrenia spectrum illness.”
She noted that there is evidence suggesting the immune system may play a role in the pathogenesis of schizophrenia, and research has shown that pneumonia and infection are among the leading causes of premature mortality in this population.
As well, several potential risk factors disproportionately affect people with serious mental illness, including an increase in the prevalence of medical comorbidities such as cardiovascular disease and diabetes, socioeconomic disadvantages, and barriers to accessing timely care. Prior studies have also found that people with SMI are less likely to receive preventive care interventions, including vaccination, said Nemani.
However, these factors are unlikely to fully account for the increased risk found in the study, she said.
“Our study population was limited to people who had received treatment within the NYU Langone Health System. We took a comprehensive list of sociodemographic and medical risk factors into account, and our research was conducted prior to the availability of COVID-19 vaccines,” she said.
Further research is necessary to understand what underlies the increase in susceptibility to severe infection among patients with schizophrenia and to identify interventions that may mitigate risk, said Nemani.
“This includes evaluating systems-level factors, such as access to preventive interventions and treatment, as well as investigating underlying immune mechanisms that may contribute to severe and fatal infection,” she said.
The researchers could not validate psychiatric diagnoses or capture deaths not documented in the electronic health record. In addition, the limited sample size precluded analysis of the use of individual antipsychotic medications, which may differ in their associated effects.
“It’s possible individual antipsychotic medications may be associated with harmful or protective effects,” said Nemani.
The authors have disclosed no relevant financial relationships.
JAMA Psychiatry. Published September 22, 2021. Full text