Antidepressant Reduced Hospitalizations in COVID-19 Patients

A generic antidepressant has shown potential in treating patients with COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19 in Brazil, investigators assessed the efficacy of fluvoxamine versus placebo in preventing hospitalization.

They found that the proportion of patients observed in a COVID-19 emergency setting for more than six hours or transferred to a tertiary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (11% versus 16%), according to recently published results in The Lancet.

The mortality rate was also lower among patients who received fluvoxamine. There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis. There was one death in the fluvoxamine group and 12 deaths in the placebo group for the per-protocol population.

“Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalization,” investigators wrote. “Given fluvoxamine’s safety, tolerability, ease of use, low cost, and widespread availability, these findings might influence national and international guidelines on the clinical management of COVID-19,” they noted.

High-risk symptomatic adults confirmed positive for SARS-CoV-2 from 11 clinical sites in Brazil with a known risk factor for progression to severe disease were included. A total of 180 patients were randomly assigned to the fluvoxamine arm and 251 patients were in the placebo arm.

Although not approved to treat infections, fluvoxamine has an anti-inflammatory effect. It binds to the sigma-1 receptor in immune cells, resulting in reduced production of inflammatory cytokines, according to the National Institutes of Health.

The underlying mechanism of fluvoxamine for COVID-19 remains uncertain, the authors of The Lancet paper wrote. “Although hypotheses include several potential mechanisms, the main reason for the initial study of fluvoxamine as a treatment of COVID-19 was its anti-inflammatory action through activation of the S1R,” they wrote.

S1R is an endoplasmic reticulum (ER) chaperone membrane protein involved in many cellular functions, including regulation of ER stress response–unfolded protein response and regulation of cytokine production in response to inflammatory triggers.

A second mechanism could be fluvoxamine's antiplatelet activity. SSRIs can prevent loading of serotonin into platelets and inhibit platelet activation, which might reduce the risk of thrombosis. The antiplatelet effects can be cardioprotective, the researchers wrote.