Will the Antidepressant Fluvoxamine Fight COVID-19?

Since the beginning of the pandemic, people have been looking for treatments that might help control the coronavirus. That was well before vaccines took center stage. Now, everyone is waiting for oral antiviral drugs to show up on pharmacy shelves. Ever since the FDA issued Emergency Use Authorization (EUA) for Pfizer’s Paxlovid (nirmatrelvir + ritonavir) and Merck’s Legevrio (molnupiravir), patients with COVID want to know: “where are these breakthroughs?” The answer: “hard to find!” These pills are in very short supply! What about a very old and inexpensive medication called fluvoxamine? And what’s the latest on ivermectin?

A Quick History of Fluvoxamine:

When most health professionals think of a “new” generation of antidepressants, they probably name fluoxetine (Prozac). It was approved by the FDA at the end of 1987 and marketed by Eli Lilly in the US in 1988. This SSRI (selective serotonin reuptake inhibitor) made the cover of Newsweek (“The Promise of Prozac,” March, 1990).

Lost in the mists of time is the first SSRI to treat depression. Solvay Pharmaceuticals marketed fluvoxamine in Switzerland in 1984, almost four years before Prozac hit the US market. Although it has been used to treat depression in dozens of other countries, the FDA approved Luvox exclusively to treat OCD (obsessive compulsive disorder) in 1994.

Why Would a Drug for OCD or Depression Fight COVID?

Fluvoxamine does more than allow serotonin to build up in the brain. It has the ability to attach to sigma-1 receptors. Such molecular structures activate cytokine production, which can sometimes get out of hand during a COVID infection. Because the drug has the ability to modulate the immune response, that may explain how it might prevent mild coronavirus infections from becoming more serious.

A small study published in JAMA (online, Nov. 12, 2020) disappeared almost without a trace. It compared fluvoxamine to placebo for treating COVID patients. The results were surprisingly good. Out of 152 people with COVID -19, 80 took fluvoxamine and 72 took a look-alike placebo pill. Six of those on placebo had serious clinical deterioration, compared to none of those on fluvoxamine.

How Excited Should We Be About Fluvoxamine?

The JAMA research is what I would characterize as a pilot study or proof of concept. Interesting. Maybe even intriguing, but not yet convincing. There is another kind of fluvoxamine study described in a segment of 60 Minutes. It involves jockeys and people who work at a race track.

To learn more about this fascinating research and how it got started you may wish to watch a recent segment from 60 Minutes titled:

“Finding A Possible Early Treatment for COVID-19 In A 40-Year-Old Antidepressant” (March 7, 2021)

The Future for Fluvoxamine vs. COVID-19:

The first study published in JAMA was followed by a larger trial to confirm whether fluvoxamine truly has significant benefits against COVID. A large randomized controlled trial from Brazil produced surprisingly good results (Lancet Global Health, Jan. 2022).

The authors conclude:

“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.”

“Given fluvoxamine’s safety, tolerability, ease of use, low cost, and widespread availability, these findings might influence national and international guidelines on the clinical management of COVID-19. This study is only the second study to show an important treatment benefit for a repurposed drug in the early treatment population.”

Despite these positive results, American public health authorities seem uninterested. We find that puzzling.

Fluvoxamine Side Effects:

Doctors prescribe this generic medicine primarily to treat obsessive-compulsive disorder. Because it has been around since 1984, doctors know what sorts of side effects to expect. Here are some highlights.

All SSRI-type antidepressants now come with a suicide warning.

Even though this drug is not officially an antidepressant in the US, it still carries a strict caution mandated by the FDA:

“Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.”

Other Fluvoxamine Adverse Reactions:

Nausea (9%); Vomiting (2%)
Insomnia (4%)
Tiredness (4%)
Headache (3%)
Nervousness, agitation (2%)
Weakness, lack of energy (2%)
Anxiety (1%)
Abdominal pain, loss of appetite, indigestion, diarrhea (1%)
Dizziness (1%)
Dry mouth (1%)
Tremor
Sexual side effects (reduced libido, lack of orgasm, erectile dysfunction)

We suspect that some of these side effects are higher than the FDA’s official prescribing information describes. For example, dry mouth, nervousness, nausea, dizziness and sexual side effects are probably substantially more common. That said, anyone who might be prescribed fluvoxamine for COVID-19 is likely to take it for a relatively short period of time (roughly 10 days). Such complications are more likely with longer exposure. Prescribers must evaluate the potential for drug interactions very carefully.

What About Ivermectin?

Before the pandemic began, most Americans had never heard of ivermectin. A few pet owners might have recognized the name Heartgard. That’s because they give it to their dogs to prevent heartworm. They probably didn’t realize that ivermectin is the active ingredient. Today, ivermectin may be the most controversial drug in the US.

What is ivermectin? Fifty years ago, a Japanese scientist studying soil microbes teamed up with a researcher from Merck to identify an anti-parasitic compound made by bacteria. In 2015, Drs. Omura and Campbell accepted the Nobel Prize for their discovery.

The drug is widely used in veterinary medicine. Human diseases caused by parasites, such as lice and scabies, also respond to treatment.

Most impressively, ivermectin helps control the parasite that causes river blindness. This condition has been nearly eradicated in Latin America and parts of Africa due to ivermectin.

The Ivermectin Controversy:

So why is this very old drug suddenly so controversial? For the last year and a half, many people have been clamoring for its use against COVID-19.

For example, Marilyn wrote:

“Why not make ivermectin more accessible in the US? It keeps people out of the hospital, relieving the stress on the health care system. Instead, though, I keep reading that it’s a dangerous unproven protocol.”

Some doctors have started prescribing ivermectin. Barbara reports:

“My physician wants me to take 12 mg [ivermectin] twice a week from a compounding pharmacy prophylactically for antiviral activity against COVID.”

The only problem with this or any other ivermectin regimen is that we lack evidence to support it. We hoped from early on to see data showing that the antiviral activity ivermectin exhibited in laboratory test tubes would translate into clinical effectiveness. So far, the clinical trials have been disappointing or inconclusive.

The most recent systematic review and meta-analysis published in the journal Diagnostics (Dec. 14, 2021) offered this assessment:

“In conclusion, the available evidence continues to be not adequate to support the use of ivermectin for the treatment of COVID-19 in clinical practice.”

The authors are from Italy and presumably have no political agenda regarding ivermectin.

They note that more studies are underway and that:

“it would be better [to] wait [for] further evidence before concluding that ivermectin has no place in COVID-19 treatment.”

People Insist Ivermectin Is Working:

Many comments on this website are from people who maintain that ivermectin is a miracle. That despite the lack of large, well-controlled clinical trials. Many point to India and and insist that the rapid drop in COVID cases was due to ivermectin.

Rod offers a pretty typical response to our concerns about inadequate data:

“It seems quite likely that the dramatic decline in cases in India was the result of the widespread use of the anti-covid kits [containing ivermectin] distributed across India and taken by a majority of the population, not just those already infected.”

It is not clear that ivermectin has truly been “distributed across India.” Moreover, the latest graph from the Johns Hopkins Coronavirus Resource Center shows that India is also experiencing a rapid increase in COVID cases. On January 9, 2022, there were a reported 179,723 new cases. That is up from 6,358 on December 27, 2021. If you check the news from India you will realize that cases are climbing rapidly. Here is The Times of India (Jan. 11, 2022). Public health authorities are recommending vaccinations and curfews. I have been searching for a discussion of distribution of “ivermectin kits” and have so far not found any such mention.

Final Words:

We are discouraged that large, well-conducted trials of ivermectin have been so slow to appear. That is the only way we can learn for sure whether this drug can really help people recover from a COVID infection. We also hope that public health authorities will look at the fluvoxamine data and consider the potential for this old and inexpensive drug to treat COVID cases.

You can learn more about the new oral antiviral drugs Paxlovid and Legevrio at this link.

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