Safety and efficacy of fluvoxamine in COVID-19 ICU patients: An open label, prospective cohort trial with matched controls

Abstract

Aims: Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and sigma-1 receptor agonist, has so far shown promise in the prevention of COVID-19 progression as an early treatment option in three trials. The aim of this study was to evaluate the safety and efficacy of fluvoxamine in COVID-19 patients if administered later in the course of the disease.

Methods: The study was designed as an open-label, prospective cohort trial with matched controls. In April and May 2021, 51 ICU COVID-19 patients hospitalised in the University Hospital Dubrava and University Hospital Centre Zagreb, Croatia, were treated with fluvoxamine 100 mg three times daily for 15 days in addition to standard therapy and they were prospectively matched for age, gender, vaccination against COVID-19, disease severity and comorbidities with 51 ICU controls.

Results: No statistically significant differences between groups were observed regarding the number of days on ventilator support, duration of ICU or total hospital stay. However, overall mortality was lower in the fluvoxamine group, 58.8% (n = 30/51), than in the control group, 76.5% (n = 39/51), HR 0.58, 95% CI (0.36-0.94, P = .027).

Conclusion: Fluvoxamine treatment in addition to the standard therapy in hospitalised ICU COVID-19 patients could have a positive impact on patient survival. Further studies on the effects of fluvoxamine in COVID-19 patients are urgently required.

Keywords: COVID-19; ICU; SARS-CoV-2; SSRI; clinical trial; fluvoxamine; intensive care.

FIGURE 1

Proposed mechanisms of action of fluvoxamine in COVID‐19. Created with BioRender.com

FIGURE 2

Kaplan–Meier survival curves of COVID‐19 ICU patients (n = 51) treated with fluvoxamine + standard therapy in comparison to patients (n = 51) treated with standard therapy alone; HR 0.58, 95% CI (0.36–0.94, P = .027)