Adjunctive Fluvoxamine Ineffective Against Clinical Deterioration in COVID-19

Results of a study published in the International Journal of Infectious Diseases show that the addition of fluvoxamine to favipiravir is ineffective for preventing severe disease progression in patients with mild to moderate COVID-19 infection.

Researchers in Thailand conducted an open-label, randomized, controlled trial from June 2021 to February 2022 to assess the effectiveness of adjunctive fluvoxamine among patients with mild to moderate COVID-19 infection. Eligible patients were adults with polymerase chain reaction-confirmed COVID-19 infection who had at least 1 respiratory-related symptom. Patients with mild COVID-19 infection were randomly assigned 1:1 to receive either fluvoxamine (50 mg twice daily) in combination with favipiravir for 10 days or favipiravir alone. A second group of patients with moderate infection were randomly assigned 1:1 to receive either fluvoxamine in combination with favipiravir plus dexamethasone or only favipiravir plus dexamethasone. Logistic regression was used to assess the time between treatment initiation and clinical deterioration, and a multilevel regression model was used to compare patients in treatment arms with those in control arms.

A total of 266 patients were included in the analysis, of whom 132 had mild COVID-19 and received fluvoxamine plus favipiravir and 134 had mild infection and received favipiravir monotherapy. Of 61 patients with moderate COVID-19 infection, 30 received fluvoxamine in combination with favipiravir plus dexamethasone, and 31 received only favipiravir plus dexamethasone.

At day 5 following treatment initiation, there was no difference in the rate of nonclinical deterioration observed between patients with mild COVID-19 infection who received fluvoxamine plus favipiravir vs favipiravir monotherapy (100% vs 97%; P =0.059). The rate of nonclinical deterioration also did not significantly differ among patients with moderate COVID-19 infection who received fluvoxamine in combination with favipiravir plus dexamethasone vs favipiravir plus dexamethasone (83.9% vs 86.7%; P =1.000).

Further analyses showed no significant differences in the need for supplemental oxygen or hospitalization rates among patients in both the mild and moderate COVID-19 treatment arms, at both days 14 and 28 after treatment initiation. Overall, there were no mortality events reported, and no patient required intensive care unit admission or mechanical ventilation.

Adjunctive fluvoxamine therapy was associated with no significant benefits in virologic, radiologic, or immunomodulatory outcomes.

There were no severe adverse events reported among patients in both treatment arms. However, at day 14, patients with mild COVID-19 infection who received favipiravir monotherapy had higher uric acid levels, compared with those who received fluvoxamine plus favipiravir.

Study limitations include the enrollment of patients during the early phase of infection, potentially resulting in a population with less severe disease. Other limitations include the lack of placebo control and the open-label study design.

According to the researchers, “FVX [fluvoxamine] treatment could not demonstrate additional benefits in radiological improvement, reducing inflammatory markers, decreasing viral shedding, and providing immunomodulatory effects.”

This article originally appeared on Infectious Disease Advisor