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Should Doctors Start Prescribing Fluvoxamine for COVID?

Research shows that fluvoxamine for COVID is helpful. What about fluoxetine (Prozac) for COVID? A new study suggests that it too may work!
Should Doctors Start Prescribing Fluvoxamine for COVID?
Close up detail of foil packet of green and white prozac painkiller tablets on table surface

A few weeks ago we wrote about a drug that has flown below the radar: fluvoxamine for COVID. There are now decent data to support this old, affordable medication in the fight against the coronavirus. A randomized controlled trial was conducted in Brazil. It involved nearly 1500 people with COVID-19. Those taking fluvoxamine were less likely to be hospitalized or to die. Now a new study published in JAMA Network Open, November 14, 2021 suggests that a chemical cousin, fluoxetine (Prozac), may also be beneficial.

What About Other Antidepressants?

Most people have never heard about fluvoxamine. That’s because it has never been approved for the treatment of depression in the US. It was completely dwarfed by its chemical cousin fluoxetine (Prozac). Everyone knows about Prozac. Fluvoxamine is a mystery.

Not surprisingly, readers wanted to know if other antidepressants might also work against COVID.

Monica asks: Any thoughts about Prozac, Lexapro, or other SSRI’s perhaps working just as well [as fluvoxamine]?

You will read in a moment about the data from Brazil on fluoxamine. Here’s the data from California researchers this week on fluoxetine. This study was published in JAMA Network Open, November 14, 2021 and it analyzed electronic health records of more than 83,000 people. Those who were taking a selective serotonin reuptake inhibitor (SSRI), especially fluvoxamine or fluoxetine, were less likely to die from COVID-19.

How Could Prozac Help Against COVID?

The researchers report that:

“We observed a small, statistically significant reduction of 8%in the RR [relative risk] of mortality among patients with COVID-19 prescribed SSRIs when compared with matched control patients. Our subgroup analysis found a statistically significant reduction of 28% in the RR of mortality for the patients treated with fluoxetine and 26% for the patients treated with fluoxetine or fluvoxamine.”

They offer this mechanism of action:

“Several mechanisms by which SSRIs can reduce the severity of COVID-19 symptoms have been proposed in the literature. The severe respiratory illness of COVID-19 is primarily triggered by an intense proinflammatory host response. Selective serotonin reuptake inhibitors may benefit patients with COVID-19 owing to the link between serotonin and the immune system. More specifically, severe outcomes of COVID-19 have been associated with several proinflammatory cytokines, including interleukin 6, whose increased levels contribute to the cytokine storm. Various studies have indicated that SSRIs and specifically fluoxetine can decrease levels of these cytokines and interleukin 6 signaling activity.”

An Early Signal: Fluvoxamine for COVID:

Fluvoxamine is also an SSRI (selective serotonin re-uptake inhibitor). That’s a mouthful, but if I say Prozac-like drug, you should instantly recognize a category of medications that revolutionized the treatment of depression.

Eli Lilly launched Prozac, also known as fluoxetine (please note the name similarity with fluvoxamine) in January 1988. It became the most prescribed antidepressant in the US, if not the world. Prozac turned into a household word.

Luvox (fluvoxamine), on the other hand, has flown below the radar. Fluvoxamine was actually marketed by Solvay Pharmaceuticals in Switzerland in 1984 under the brand name Floxyfral. In other words, it beat Prozac to international market by four years.

In Europe and many other countries, doctors have long prescribed fluvoxamine for depression. That’s not the case in the US. The brand Luvox was launched in the United States in 1994 exclusively for the treatment of OCD (obsessive compulsive disorder).

I have long wondered why the manufacturer never asked the FDA for approval to treat depression. Perhaps the drug company felt that Luvox could not compete effectively against Prozac. To this day, fluvoxamine only has FDA’s blessing for the treatment of OCD, though I suspect that it would work about as well as fluoxetine for depression.

The brand name drug Luvox is no longer on the market. That may be in part because of a tale of woe and intrigue associated with the Columbine high school shootings. The shooter, Eric Harris, was taking Luvox for his OCD when he committed that atrocity. The brand name drug disappeared from the market in 2002. Generic fluvoxamine continues to be available by a number of manufacturers at a very reasonable price.

Enough History! What About Fluvoxamine for COVID?

We got interested in fluvoxamine for COVID after watching a segment on 60 Minutes (March 7, 2021) titled:

“Finding a Possible Early Treatment for COVID-19 in a 40-Year-Old Antidepressant.” 

There was also a preliminary study published in JAMA, Nov. 12, 2020). It was titled:

“Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial”

The authors concluded their RCT with this statement:

“In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.”

New Research on Fluvoxamine for COVID:

I wrote about fluvoxamine for COVID back on March 23, 2021. I pointed out that the JAMA study “disappeared almost without a trace.” You can read that article and learn more about fluvoxamine side effects at this link.

Will the Antidepressant Fluvoxamine Fight COVID-19?
Fluvoxamine (Luvox) has been marketed as an antidepressant since 1984. Why would this very old SSRI offer some promise against COVID-19?

While ivermectin captured headlines and ignited passions, fluvoxamine remained virtually invisible. Nevertheless, the research continued. Today, fluvoxamine is making headlines around the world.

Fluvoxamine for COVID (The Lancet):

The results of a large randomized controlled trial (RCT) were just published in The Lancet (Oct. 27, 2021). Scientists conducted the study at 11 clinical sites in Brazil. There were 741 patients in the fluvoxamine arm and 756 patients “allocated” to placebo.

The researchers report:

“This is, to the best of our knowledge, the first large, randomised controlled trial to test the efficacy of fluvoxamine for acute treatment of COVID-19. We found a clinically important absolute risk reduction of 5·0%, and 32% RR [relative risk] reduction, on the primary outcome of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19, consequent on the administration of fluvoxamine for 10 days.”

“Our trial has found that fluvoxamine, an inexpensive existing drug, reduces the need for advanced disease care in this high-risk population. A 10-day course of fluvoxamine costs approximately US$4 even in well-resourced settings. Our study compares favourably with the treatment effects of more expensive treatments including monoclonal antibodies for outpatient treatment.”

“There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis. There was one death in the fluvoxamine group and 12 in the placebo group for the per-protocol population.”

The Bottom Line “Interpretation” in The Lancet

“Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.”

The People’s Pharmacy Perspective on Fluvoxamine for COVID:

We were intrigued by the original study of fluvoxamine for COVID that was published in JAMA on November 12, 2020. At that time I described the side effects of fluvoxamine here.

I concluded with these final words:

“We are eager to see more well-controlled trials of medications against COVID-19. Just because we have several vaccines that look promising does not mean we should stop searching for effective antiviral medications or immune system modulators. If vaccines ever stop working, it would be extremely helpful to have drugs to treat complications of the coronavirus waiting in the wings.”

How do I feel now about the use of fluvoxamine for COVID? Much more optimistic. Two randomized controlled trials suggest that the drug is working against the coronavirus. The most recent one is large enough to be meaningful.

The authors of The Lancet study admit that “The underlying mechanism of fluvoxamine for COVID-19 disease remains uncertain.” There may be an anti-inflammatory component to the drug that is beneficial. Another possibility is that the antiplatelet activity of the drug prevents blood clots. The drug also raises melatonin levels in the body and melatonin may be helpful against COVID-19.

Whatever the mechanism, I am feeling much more optimistic about fluvoxamine and fluoxetine for COVID. These drugs are incredibly affordable. We look forward to comparing data from the study in Brazil with data on the antiviral drug molnupiravir being developed by Merck. Even more intriguing would be a study to determine if the two drugs might work together synergistically to fight off COVID complications.

The bottom line: in a few large, randomized controlled trials, oral medicines work against the coronavirus. We expect emergency use authorization for molnupiravir in coming weeks. Fluvoxamine and fluoxetine are available now. It would be helpful if the FDA and/or the CDC were to make some statement about their use against COVID to guide health care providers.

What Do You Think?

We would love to get your response to our articles on fluoxetine and fluvoxamine for COVID. Please share your thoughts in the comment section below. If you think this article offers valuable information not available elsewhere, please share it with friends and family. They may also value our article with detailed information about fluvoxamine side effects at this link.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
  • Reis, G., et al, "Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial," Lance, Oct. 27, 2021, DOI:https://doi.org/10.1016/S2214-109X(21)00448-4
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