An effective antidepressant against Covid-19? The evidence is piling up

• The therapeutic arsenal against Covid-19 should experience a boom in 2022.

• While all eyes are on Paxlovid, a Pfizer pill that will arrive in France at the end of January, a team of French researchers is fighting to publicize the promising results of a curative (and not preventive) treatment: an antidepressant named Fluvoxamine.

• 20 Minutes

  deciphers the advantages and disadvantages of this treatment, which is not yet prescribed in France against the coronavirus.

  But who could enrich the range of solutions for patients at risk?

“We have the opportunity to finally have a real “game changer” in treatments against Covid-19”, enthuses Nicolas Hoertel, professor of Psychiatry at the University of Paris and at the AP-HP.

One might think that this psychiatrist and modeler is talking about Paxlovid, Pfizer's anti-Covid pill which is due to arrive in France.

But there is another particularly interesting lead: Fluvoxamine, an antidepressant that seems to be proven to prevent serious cases of Covid-19.

Observational studies and four clinical trials

The story begins in France, in the spring of 2020, with a question: why were psychiatric patients so little affected by Covid-19 during the first wave? Thanks to data from 36 AP-HP hospitals, Nicolas Hoertel and his team published an observational study in July 2020 (taking data from hospitalized patients) showing, for patients on antidepressants, a risk of intubation or death. decreased by more than 40% compared to the other patients. Since then, the hypothesis has been strengthened and refined.

“Several observational studies come to the same conclusion as our study: certain antidepressants reduce the risk of dying or being intubated by 50%, explains the psychiatrist.

With heterogeneity according to the antidepressants, the best being Fluoxetine, better known as Prozac, which achieves a protection of more than 70%.

Problem, research now focuses more on a cousin of Prozac, Fluvoxamine, less prescribed in France against depression.

90% lower risk of dying

Four published clinical trials have enriched the data on Fluvoxamine. "Among them, two open studies (the doctor and the patient know all the drugs), carried out on a hundred patients, gave spectacular results: potentially 100% reduction in the risk of clinical worsening in outpatients and 42% reduction in the risk of death in intensive care. “Conclusions supported by two double-blind randomized controlled trials, the ultimate in research. The first, published in the scientific journal

concluded that it was 100% effective in reducing the risk of hospitalization, but on a small sample.

The second, which is part of the Together study, carried out in Brazil and including 1,497 symptomatic outpatients, shows that Fluvoxamine reduces the risk of being hospitalized or being monitored for 6 hours in the emergency department by 32%. . A limited result that left some researchers skeptical, embarrassed by this unusual criterion. But “if we only look at patients who have taken the treatment well (80% of them), the risk of being hospitalized drops by 66% and of dying by 90%. What is very encouraging is the consistency and reproducibility of the result: several studies, in several countries, come to the same conclusion”, continues the researcher at Inserm.

Moreover, some were not mistaken.

The World Health Organization launched a systematic review on Fluvoxamine on December 1, 2021. Some doctors are already prescribing it in Brazil, Malaysia, India, the United States, Canada… And three North American universities are joining the Fluvoxamine in treatments against Covid-19.

All specify that this antidepressant can be prescribed if the patient, likely to have severe Covid, cannot be treated with monoclonal antibodies.

However, we now know that all monoclonal antibodies, except Evusheld, do not protect against Omicron.

The situation is therefore new, especially for immunocompromised people.

An effective, inexpensive treatment known for thirty years

Will this antidepressant be as effective against Omicron, knowing that these clinical trials were conducted before the arrival of this new variant? “The mechanism of action of these molecules suggests that the efficacy of this treatment is insensitive to the variants, reassures Nicolas Hoertel. So it would work well on Omicron. Several studies to verify this hypothesis are being conducted in parallel in Brazil, India and the United States. We should therefore know more soon.

The psychiatrist insists on two other advantages: “Fluvoxamine is 3 or 4 euros for ten days. For the Paxlovid, we would reach 570 euros for a complete treatment. This is not for poor countries! This drug is likely to be reserved for the best vaccinated population… Fluvoxamine, or its cousin Fluoxetine, is available everywhere in the world, right now. However, Nicolas Hoertel does not seek to oppose antidepressants and Pfizer pills. “It will probably be necessary to use both. »

Still, antidepressants are known for their undesirable effects: nausea, diarrhea, migraine, agitation, insomnia… “As with any medication, there may indeed be undesirable effects, but it is generally well tolerated, nuance Nicolas Hoertel.

Especially since it is a treatment well known to doctors, for which we have thirty years of hindsight, and which will be prescribed for a short time.

Specifically, in the Together trial, there was no difference in side effects between the Fluvoxamine group and the placebo group.

»

Could France soon adopt this curative treatment?

“All avenues of treatment are interesting, assures Bruno Lina, virologist and member of the Scientific Council.

But some products, supposed to be a game-changer, have proven to be ineffective.

I have no information to say if this antidepressant works or not.

“In the coming months, we will see the arsenal to fight against Covid-19 expand, predicts Sandrine Sarrazin, researcher at Inserm.

It is very interesting to work in this field of repositioning, because these molecules have already been tested, we know the doses, the side effects and we can produce and prescribe them quickly.

»

And Nicolas Hoertel to regret the lack of interest in France.

“We start from afar with a lot of a priori on antidepressants.

I think there is also a “hydroxychloroquine effect”, with the runaway of the machine and the cold shower… ”

The Ministry of Health specifies to

that “the health authorities are in contact with the clinicians carrying out the project in France, in particular with a view to conducting a [new] clinical trial.

“A situation that could change soon…

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• Psychiatry

• Covid-19

• Coronavirus

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