Fluvoxamine Prevents COVID-19 Hospitalizations in Outpatient Settings

A systematic review of clinical trials found a high probability that fluvoxamine prevented COVID-19 hospitalizations in outpatient settings.

The COVID-19 pandemic has drained hospital staff and resources, creating a need for treatments that are effective in outpatient settings. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) and a σ-1 receptor (S1R), has previously been proven to offer anti-inflammatory and antiviral effects.

Research published this week in JAMA systematically analyzed fluvoxamine outpatient trials to determine whether the therapy reduced hospitalizations. COVID-19 infections seem to have temporarily plateaued, but finding a safe and effective treatment that is available, accessible, and affordable remains high priority.

The investigators searched the World Health Organization International Clinical Trials Registry Platform, as well as ClinicalTrials.gov, to perform a systematic review and meta-analysis of all registered clinical trials of fluvoxamine for COVID-19 treatment. They identified 19 candidate randomized controlled trials, and the final analysis included 3 studies that met the inclusion criteria. The primary outcome of interest was all-cause hospitalization.

After conducting Bayesian analyses, the overall probability that fluvoxamine reduced the risk of COVID-19 hospitalization ranged from 94.1-98.6%. In the frequentist meta-analysis, the pooled RR in favor of fluvoxamine was 0.75.

The investigators emphasized that their certainty of the evidence was moderate. All 3 included trials were placebo-controlled randomized trials, but some findings were inconsistent. Currently ongoing studies will add to what is known about the efficacy of fluvoxamine for COVID-19 treatment. The trials are testing fluvoxamine at a dosage of 50 mg twice daily, which if unsuccessful could indicate that 100 mg twice daily is the minimum effective dose.

The investigators estimated that high-risk COVID-19 outpatients could obtain fluvoxamine for $1 a day, making it a viable alternative for persons who do not have access to monoclonal antibodies, direct antivirals, or clinical trials. The most common side effects of fluvoxamine are gastrointestinal, including nausea, vomiting, diarrhea, and anorexia, and central nervous system complaints, such as headache, somnolence, dizziness, and nervousness.

“A moderate strength recommendation in favor of fluvoxamine could be considered in certain clinical scenarios,” the study authors wrote. “Based on currently available clinical trial data, we demonstrate high probability of an association between fluvoxamine and at least a moderate reduction in COVID-19 hospitalizations, under a variety of assumptions. By comparison, outpatient trials with hydroxychloroquine and ivermectin have not shown any efficacy and yet these agents continue to be prescribed.”