Fluvoxamine May Reduce COVID-19 Hospitalizations and ED Visits

Fluvoxamine is safe for treating non-hospitalized patients with COVID-19 and may lead to a reduction in hospitalizations and fewer emergency department (ED) visits, according to a meta-analysis published in the Journal of Infection and Public Health.

Fluvoxamine, a selective serotonin reuptake inhibitor which has been used for the treatment of depression, has an anti-inflammatory effect. It has also been found to produce an antiviral effect and may ameliorate cytokine response. Additionally, fluvoxamine can inhibit acid sphingomyelinase activity, attenuate SARS-CoV-2 cell entry, and may decrease SARS-CoV-2 replication. Investigators sought to examine the use of fluvoxamine to treat non-hospitalized patients with COVID-19. The primary endpoint was the rate of hospitalization or ED visits.

The investigators conducted a systematic review and meta-analysis, searching Scopus, Cochrane Library, Embase, Ovid Medline, Web of Science, and PubMed databases and ClinicalTrials.gov for clinical studies published before the last week of June 2022. Only studies comparing fluvoxamine safety and efficacy with alternatives or placebos to treat non-hospitalized patients with COVID-19 were included for analysis. The researchers excluded reviews or meta-analyses, studies lacking adequate data for outcome analysis, and poster or conference abstracts.

The investigators found 4 studies that included 912 patients who received fluvoxamine (who comprised the study group for the meta-analysis) and 902 patients who received placebos or no therapy (who comprised the meta-analysis control group). Among the included studies, 3 were randomized controlled trials (RCTs) and 1 was a prospective, nonrandomized cohort study with fluvoxamine use at patient discretion. One study was conducted in Brazil, 1 in South Korea, and 2 in the US. A placebo was used as comparator in the RCTs.

In 2 of the RCTs, more than 50% of patients had obesity. In 2 of the studies, patients were unvaccinated, and in the other 2 studies vaccine status was not applicable. The 2 most common underlying diseases among all patients were diabetes and hypertension. The researchers acknowledged that 2 of the included studies had bias due to deviation from intended interventions, and 1 of the studies had bias concerns for multiple domains.

The investigators found a lower risk of hospitalization and ED visits in the study group vs control group (odds ratio [OR] 0.59; 95% CI, 0.44-0.79; I²=26%). The rate of hospitalization in patients receiving fluvoxamine (8.8%) was significantly lower than the control group hospitalization rate (14.5%) in pooled analysis (OR 0.69; 95% CI, 0.51-0.94; I²=36%). In a sensitivity test including just the 3 RCTs, the difference remained significant and fluvoxamine was associated with lower risk of hospitalization or ED visits than placebo (OR 0.63; 95% CI, 0.47-0.85; I²=0.0%).

The meta-analysis also found nonsignificant differences between the study vs control group linking fluvoxamine to lower risk for mechanical ventilation, intensive care unit admission, and mortality. A similar risk of adverse events was seen with fluvoxamine vs control treatment.

Analysis limitations include the use of data with high heterogeneity as the basis for the meta-analysis; the limited number of included studies; the use of 3 underpowered studies; and the exclusion of fully vaccinated individuals from 3 of the trials.

Investigators concluded that “Fluvoxamine can be safely used in nonhospitalized patients with COVID-19 and can reduce the hospitalization rate or ED visits in these patients.” While investigators found fluvoxamine to be safe for treating COVID-19 infection, they noted that “the present evidence is insufficient to support recommending fluvoxamine in the treatment of non-hospitalized patients with COVID-19.”