Antidepressant reduces hospitalisations in high-risk COVID-19 patients, study shows

Anti-inflammatory properties of fluvoxamine may explain why patients who received the treatment were less likely to be hospitalised with COVID-19 than patients given placebo.
Hospitalised COVID-19 patient

The selective serotonin reuptake inhibitor (SSRI) fluvoxamine could reduce the need for hospitalisation in high-risk patients with early diagnosed COVID-19, a Brazilian study has shown.

The randomised study, published in The Lancet Global Health on 27 October 2021, found an absolute risk reduction of 5%, and a relative risk reduction of 32%, in hospitalisation for high-risk patients with COVID-19 treated with fluvoxamine, compared with those given a placebo.

In the ‘TOGETHER’ trial, 1,497 adults with cardiovascular disease or diabetes and confirmed, symptomatic COVID-19 were randomly assigned to receive either fluvoxamine (100mg twice daily for ten days) or placebo.

Some 28 days after first receiving treatment, the researchers found that the number of patients requiring hospitalisation was lower for the fluvoxamine group compared with the placebo group (79 [11%] of 741 vs. 119 [16%] of 756).

Fluvoxamine is currently used to treat depressive illness and obsessive compulsive disorder. The authors of the study said that the trial was, “to the best of our knowledge”, the first large, randomised controlled trial to test the efficacy of the drug for acute treatment of COVID-19.

The underlying mechanism of fluvoxamine for COVID-19 disease “remains uncertain”, they added, although hypotheses include several potential mechanisms, primarily the anti-inflammatory action of the drug.

The authors concluded that in vitro and animal studies were needed to help clarify the most probable mechanism.

“In short, fluvoxamine not only binds to the serotonin transporter but also inhibits the sigma-1 receptor involved in cytokine production and the immune response,” explained Colin Davidson, professor of neuropharmacology and head of school of pharmacy and biomedical sciences at the University of Central Lancashire.

“Fluvoxamine could reduce an out of control immune response, the so-called ‘cytokine storm’, and thereby reduce hospitalisation due to COVID-19. The Lancet manuscript also suggests that fluvoxamine might have a useful effect through antiplatelet activity, reducing the chances of thrombosis,” he added.

Gilmar Reis, a researcher based in Belo Horizonte, Brazil, and also co-principal investigator of the trial said that the results were “consistent” with earlier, smaller trials.

“Given fluvoxamine’s safety, tolerability, ease of use, low cost, and widespread availability, these findings may have an important influence on national and international guidelines on clinical management of COVID-19.”

Edward Mills, a professor in the Department of Health Research Methods, Evidence, and Impact at McMaster University in Canada, and co-principal investigator on the trial, said the results were important, particularly for countries with low resources and limited access to vaccinations.

“Identifying inexpensive, widely available and effective therapies against COVID-19 is therefore of great importance, and repurposing existing medications that are widely available and have well-understood safety profiles is of particular interest,” he added.

READ MORE: Everything you need to know about the COVID-19 therapy trials

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Citation
The Pharmaceutical Journal, PJ, October 2021, Vol 307, No 7954;307(7954)::DOI:10.1211/PJ.2021.1.112923

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