Fluvoxamine is an antidepressant drug approved by the FDA for the treatment of depression and obsessive-compulsive disorder (OCD).. It is in the class of drugs called Selective Serotonin-Reuptake Inhibitors (SSRIs). A large multi-center observational study in France showed that SSRIs in general were protective against COVID and the drug with the greatest sigma-1 activation in the study (fluoxetine in that case) had the greatest protection. The hypothesis of the researchers at Washington University is that the protection comes from the activation of Sigma-1. S1R is known to inhibit a cytokine, a chemical in our body that gets activated in certain infections, such as Covid-19. Excessive inflammatory response, “Cytokine Storm”, was thought to be responsible for some of the complications ("Covid Pneumonia") seen in Covid-19 patients that leads to hospitalization and/or need for ventilator treatment. They chose fluvoxamine because, of all the SSRIs, fluvoxamine had the greatest activation of Sigma-1.The importance of Sigma-1 has been written about by NIH Director Francis Collins. Collins wrote "COVID-19 patients taking ...drugs ... that target SIGMAR1 were half as likely as those taking other types of ...drugs to require mechanical ventilation."
With support from CETF, a randomized, double-blind and fully remote outpatient clinical trial was conducted at the University of Washington in St. Louis, led by Eric Lenze, MD and Angela Reiersen, MD, 152 people participated in this trial, all of whom were 18 years or older, symptomatic, and diagnosed with mild forms of COVID-19. Participants were randomly assigned (1:1) to take either Fluvoxamine or a placebo. In this trial, of the 80 participants who received the drug, no patients hit the endpoint of clinical deterioration (defined as reaching blood oxygen saturation level of less than 92% and shortness of breath requiring supplemental oxygen), versus 6 people out of 72 who got the placebo and did reach the clinical endpoint. In summary, all fluvoxamine-treated patients did not meet the study endpoint. The study appeared as the lead story in JAMA on Nov 12. The Editors noted that they chose this study from over 10,000 COVID submissions received since February 2020. Interest has been high: the study was the third most popular article on JAMA for the month of December.One week after the study was published, there was a COVID outbreak at Golden Gate Fields Racetrack.
The track doctor, Dr. David Seftel, had read about the JAMA study the week before and on November 21, started offering it to the employees. At first, only 35% of the employees opted to try the drug. Two weeks later, after the employees saw first-hand what happened with people who took the medication vs. people who refused, there is a 100% acceptance rate of the drug. Employees that previously had rejected the drug changed their minds and requested the drug. In total, 48 employees refused the drug, 6 of them were later hospitalized, an 12.5% hospitalization rate. By contrast, all 77 employees who received the drug (50mg BID for 14 days) had a 0% hospitalization rate (for any reason) and all had very mild symptoms and reported no degradation in pulmonary or cognitive function. The Seftel study was published in OFID with a special "Editor's Choice" designation on February 1, 2021.
On December 22, 2020 the dean of the school of medicine at Emory University called for fluvoxamine to be used in clinical practice. On December 9, FastGrants sent this message to all grantees: "Given that fluvoxamine is relatively safe, cheap, and widely available, we’ve decided to issue a call for proposals and data pertaining to fluvoxamine. We are interested in funding any fluvoxamine RCTs that can be rapidly initiated or other relevant connected work. (We are already funding one RCT that should start soon.) If you have a related proposal, relevant data (on fluvoxamine, SSRIs, or S1R agonists more broadly), or know of anyone else who does, please also feel free to send them our way. We are eager to see both positive and negative data in this area.
CETF, FastGrants, the Skoll Foundation, and Cures Within Reach are jointly sponsoring a larger Phase 3 trial of fluvoxamine that is actively recruiting participants as of Jan 29, 2021. This is a remote trial that is available to anyone in the US and Canada..
There is no cost to enroll and you can enroll and participate from home.
1. Visit https://stopcovidtrial.wustl.edu/
2. Send your email and phone number to: firstname.lastname@example.org
Existing drugs could help treat covid-19. How do we know when to use them? (Washington Post)
These drugs might prevent severe COVID (Scientific American)