People taking a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs) were significantly less likely to die of COVID-19 than those who did not use the medicine, a large analysis of health records from 87 health care centres across the US has found.

The findings, published in the journal JAMA Network Open on 15 November, add to a body of evidence indicating that SSRIs may have beneficial effects against the worst symptoms of COVID-19, although large randomised clinical trials are needed to prove this.

"We can't tell if the drugs are causing these effects, but the statistical analysis is showing significant association," said Marina Sirota, an associate professor at University of California (UC) San Francisco, US.

The team, including researchers from Stanford University in the US, analysed electronic health records from the Cerner Real World COVID-19 de-identified database, which had information from almost 500,000 patients across the US.

This included 83,584 adult patients diagnosed with COVID-19 between January and September 2020. Of those, 3,401 patients were prescribed SSRIs. The large size of the dataset enabled researchers to compare the outcomes of patients with COVID-19 on SSRIs to a matched set of patients with diseases who were not taking them.

The study teased out the effects of age, sex, race, ethnicity, and comorbidities associated with severe COVID-19, such as diabetes and heart disease, as well as the other medications the patients were taking. The results showed that patients taking SSRI drug fluoxetine were 28 per cent less likely to die, according to the researchers.

Those taking either fluoxetine or another SSRI called fluvoxamine were 26 per cent less likely to die, they said. The study found that the entire group of patients taking any kind of SSRI was 8 per cent less likely to die than the matched patient controls. Though the effects of SSRIs are smaller than those found in recent clinical trials of new antivirals developed by Pfizer and Merck,the researchers said more treatment options are still needed to help bring the pandemic to an end.

"The results are encouraging. It's important to find as many options as possible for treating any condition," said Tomiko Oskotsky, a research scientist in Sirota's lab at Bakar Computational Health Sciences Institute (BCHSI) at UC San Francisco. "A particular drug or treatment may not work or be well tolerated by everyone. Data from electronic medical records allow us to quickly look into existing drugs that could be repurposed for treating COVID-19 or other conditions," Ostotsky added.

The study authors noted that antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. "These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality," the researchers said.

"Further research and randomised clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes," they added.