Fluvoxamine is an SSRI but also has the ability to decrease inflammation through potent activation of the sigma-1 receptor. In a murine sepsis model the drug was shown to reduce mortality, predominantly through sigma-1 activation.
Researchers in North America conducted a meta-analysis of available clinical trials comparing fluvoxamine with placebo for outpatient management of COVID-19 in order to ascertain whether early administration of the drug reduces the risk of hospitalisation.
Three randomised placebo-controlled trials were deemed eligible for inclusion in the meta-analysis: the STOP COVID 1 trial (n=152); the STOP COVID 2 trial (n=547); and the TOGETHER trial (n=1497). In all three studies the target dose of fluvoxamine was 100mg twice daily for 10−15 days.
The overall probability of association with reduced hospitalisation ranged from 94.1% to 98.6% while the probability of moderate association ranged from 81.6% to 91.8%.
Further research needed
The researchers state that their findings demonstrate high probability of an association between fluvoxamine and at least a moderate reduction in COVID-19 hospitalisations. They add that further data from ongoing studies such as the COVID-Out and ACTIV-6 trials will help to refine their findings.
They conclude: "Ongoing randomised controlled trials of fluvoxamine should continue, particularly those studying lower 50mg doses (which may be better tolerated), evaluating efficacy in vaccinated individuals, or studying the related SSRI fluoxetine, which is on the World Health Organisation's list of essential medications."