Since the early days of the pandemic, researchers have been trying to use old drugs for new tricks, raising hopes and spurring controversy. Some of these, like hydroxychloroquine, turned out to be flops, while others are still debated. Recently, another old drug called fluvoxamine has come onto the scene. MedPage Today explores how the old antidepressant has made its way to the COVID spotlight.
Fluvoxamine and the COVID Early Treatment Fund
Fluvoxamine is the poster child of the COVID-19 Early Treatment Fund (CETF). According to its founder, serial tech entrepreneur Steve Kirsch, CETF was started in April 2020 in order to fund drug repurposing research to find the fastest and most cost-effective early outpatient treatments for COVID-19. Kirsch told MedPage Today that his efforts are purely humanitarian -- almost no one was supporting this kind of research, so he stepped up to the plate.
"People have accused me of doing it out of my own self-interest. I can tell you I have done nothing but lose money on this endeavor," he said in an interview. "Pure charity, there really isn't a way to profit from this."
Kirsch, whose net worth totals about $230 million, was diagnosed with waldenstrom's macroglobulinemia in the past and has funded research for that rare blood cancer through other philanthropic efforts. He has a bachelor and master of science in engineering from MIT.
He says he has raised $5 million for CETF, starting with a tax-deductible bolus of $1 million of his own money. The biggest donors have been the Skoll Foundation ($1 million) and the Flu Lab ($1.3 million), according to an email from Kirsch. Both the Skoll Foundation and the Flu Lab were contacted by MedPage Today for comment, and did not respond.
The CETF has assembled a scientific advisory board with 12 members from academic institutions including Johns Hopkins University, Harvard Medical School, and Northwestern University. Kirsch says that the scientific advisory board has reviewed 110 grant applications so far, and has funded 14 of them.
One of these applications was for fluvoxamine in the early treatment of COVID-19, submitted by Eric Lenze, MD, a psychiatrist at Washington University in St. Louis, who is now principal investigator on a fluvoxamine trial called STOP COVID, with preliminary results published last fall in JAMA.
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is used primarily to treat obsessive compulsive disorder in adults and children ages 8 and up. It was first FDA approved in 1994, and was sold in the U.S. under the brand name Luvox until 2002. Luvox was taken off the market in the U.S. following reports that one of the Columbine shooters, Eric Harris, had been taking the drug at the time of the tragedy. Generic fluvoxamine continues to be available in the U.S.
Overall, fluvoxamine appears to be well tolerated, although it has the potential to precipitate manic episodes in susceptible people. Like all members of its class, fluvoxamine has a long list of potential drug-drug interactions, and carries a black box warning for suicidal ideation in children, adolescents, and young adults. There is also a risk for QTc prolongation and rare but potentially deadly serotonin syndrome. There has been at least one case report of acute fluvoxamine toxicity and death.
Kirsch says that earlier stage studies of fluvoxamine as a possible anti-inflammatory were convincing enough for the CETF scientific advisory board to fund Lenze's preliminary study. Results published in JAMA indicated that clinical deterioration occurred in 0% (0/80) of COVID-19 patients randomized to fluvoxamine compared with 8% (6/72) on placebo (P=0.009).
However, the study relied upon patient self-report and self-measurement of symptoms. Lenze (who reports consulting fees from Jazz Pharmaceuticals, the maker of Luvox CR) and colleagues acknowledge that they could not validly monitor the most severe baseline symptom of COVID-19 over time, and that "the potential effects of fluvoxamine on symptomatic improvement are unknown."
Promoting Fluvoxamine for COVID-19
To get the word out about fluvoxamine, Kirsch has hired the PR firm G.F. Bunting. David Satterfield, executive vice president at the company, told MedPage Today via email that a small, observational study at a California racetrack provided "a good narrative" for PR efforts.
"The L.A. Times did a piece, 60 Minutes followed, and now there's some attention," he told MedPage Today via email.
Results from the open-label racetrack study were published in February in Open Forum on Infectious Diseases. The study included 113 workers at a California racetrack who tested positive for COVID-19 and were offered fluvoxamine. Among the 65 who took fluvoxamine, none were hospitalized, compared with six of 48 (12.5%) who declined the drug (P=0.005).
Kirsch said no racetrack workers who took fluvoxamine had lingering symptoms at 14 days of follow-up, compared with 60% of workers who did not take the drug. He says there is no other explanation for these results except that fluvoxamine saves lives and prevents long COVID.
In a Twitter post, he has offered $1 million to anyone who can identify a confounder that better explains these results (the money will be donated to the winner's medical research cause of choice, he said).
On his blog, Kirsch went farther and has described fluvoxamine as "a small pill that transforms this destructive virus into a mild-mannered common cold." One post begins, "The fast, easy, safe, simple, low cost treatment for COVID that has worked 100% of the time to prevent hospitalization that nobody wants to talk about."
After providing a disclaimer, he appears to give medical advice in a post entitled "How I would Treat COVID." The post provides a type of treatment algorithm that lists 19 different drugs. Some of these, such as fluvoxamine and ivermectin, are generic. Others are investigational and only available in clinical trials.
The post also includes advice on how to get fluvoxamine from your doctor, and links to telemedicine doctors who are willing to prescribe it.
One of those telemedicine doctors is Syed Haider, MBBS, who uses a Texas telephone number but says he is currently located in North Carolina. Haider, who says he has no financial relationship with Kirsch, told MedPage Today that Kirsch approached him about fluvoxamine.
"Steve Kirsch reached out and said look at all this stuff on fluvoxamine," Haider said. "I was listed on a few websites as being willing to prescribe ivermectin. Steve Kirsch went on those websites and I think he emailed everyone who was open to alternative treatments."
Before becoming a full-time telemedicine doctor, Haider worked as a hospitalist for about 10 years. He started transitioning into telemedicine about a year ago with Teladoc, one of the nation's largest providers of telemedicine. Haider says he has permanent medical licenses in five states, and has received a pandemic waiver to provide telemedicine services in 41 states. Business for his own telemedicine site began to pick up in December 2020, after senate testimony by Pierre Kory, MD, of the Frontline COVID-19 Critical Care Alliance (FLCCC). He says many people find him through the FLCCC website, not through CETF.
"A lot of people started going online looking for someone to give them something preventative for COVID-19, so I started doing my own thing. Since January it's gotten very busy, and I've been almost 100% COVID prevention and treatment," Haider said.
These days, he sees about 30 patients per day, 7 days per week. About three to five patients per day have acute COVID-19, most of whom are receiving fluvoxamine from him. All physician phone calls or video visits cost $115, cash only. He does not accept private insurance, Medicare, or Medicaid.
60 Minutes Material, or Misinformation?
Kirsch said via email that his attempts to promote fluvoxamine are being curtailed. He says that Facebook took down one of his posts announcing his appearance on 60 Minutes. The post read: "I will be featured on 60 Minutes this Sunday talking about fluvoxamine as an effective treatment for COVID-19 to prevent hospitalization and death. Please watch and tell your friends!"
Facebook has a "Combating COVID-19 Misinformation" policy, which includes removing posts that make false claims about cures and treatments for COVID-19.
"We have also heard from public health authorities that if people thought there was a guaranteed cure or prevention for COVID-19, that could lead them to take incorrect safety measures, ignore appropriate health guidance, or even attempt harmful self-medication. This is why we don't allow false claims about how to cure or prevent COVID-19," the policy reads.
Kirsch also says that the online open publication platform Medium has deleted the last six years' worth of his content. When he appealed, he says Medium responded that his content was dangerous and terminated his account for life. He adds that SendGrid, the marketing tool used to email large lists of people, has disabled his account. Neither Medium, SendGrid, nor Facebook returned requests for comment from MedPage Today.
Kirsch adds that he has offered to pay for an emergency use authorization application for fluvoxamine on behalf of Upsher Smith, the maker of fluvoxamine, and that the company "will look at it." When approached by MedPage Today, Upsher Smith declined to comment.
Crossing the Line?
Based on the data so far, Kirsch says that he's convinced fluvoxamine will save lives. Like those who champion ivermectin, Kirsch argues that time is of the essence in the pandemic, and patients shouldn't have to wait until a phase III trial proves whether fluvoxamine works or not.
"Fluvoxamine is a highly effective anti-inflammatory treatment option which can dramatically lower hospitalization and fatality rates as well as lowering the risk of long-haul COVID and organ damage. ... There is no need to wait for the clinical trial," he writes in his blog post "How I Would Treat COVID."
But there is an ethical problem here, according to Steven Joffe, MD, MPH, chief of medical ethics at the University of Pennsylvania Perelman School of Medicine.
"The blog and FAQ are leapfrogging the evidence. No one should be promoting drug treatments for COVID until there is rigorous clinical trial evidence of their effectiveness. The ethical problem here is the misleading claims," Joffe said via email.
Unproven therapies such as fluvoxamine require study to determine their safety and effectiveness for new indications, such as outpatient treatment for COVID-19, he said.
"Most people with early COVID get better on their own, so you can't say that a drug is effective until you've shown it's better than placebo, or some other comparison, in a controlled trial," said Joffe. "One important lesson of the COVID pandemic is that promoting something to treat the disease before we know whether it's safe and effective usually leads us down a false path."