Fluvoxamine fails among the vaccinated.

The idea of repurposing existing drugs for Covid-19 remains appealing. Yet another one has fizzled out.

A chemical model of fluvoxamine, an antidepressant that showed hope for Covid-19. Getty Images.

What if we already had a miracle treatment for Covid-19 and it was right in front of us all along—some old medication sitting in our local pharmacies just waiting to be discovered as a literal panacea for all our pandemic ills?

That longing sent countless researchers headlong into investigations, ranging from superb to silly. Of the hundreds (if not thousands) of compounds considered for Covid-19, virtually all have failed to succeed in a study rigorous enough to be “practice-changing” for doctors. The only inexpensive medication I can think of that already existed prior to the pandemic that has a high-quality blinded randomized clinical trial to back it up is the steroid dexamethasone.

There have been many famous failures, though. I’m too tired of bots and trolls to get into those right now, so let’s not go there today.

One existing and inexpensive drug that I always felt had a chance to work for Covid was the anti-depressant fluvoxamine. A blinded randomized clinical trial in 2020 showed that patients who received fluvoxamine had fewer hospitalizations than those who received placebo. Some later work also suggested a benefit (in studies of mostly unvaccinated people). Despite this, the FDA rejected a request for authorization for the use of this drug, based on insufficient evidence.

I would have been miffed about this (since the data were not much worse than other drugs the FDA had given the green light to at various times, but the reality was that by the time of the decision (December 2021), we were well into the vaccine era and Delta and Omicron meant that most people would have immunity from a vaccine, the virus, or both. To me, that meant that even if the drug worked (which I was reasonably optimistic about), its clinical relevance was likely fading fast (although it could be helpful in areas with looking for less expensive oral treatments for Covid).

In the vaccine era, the results on fluvoxamine have been disappointing. One study in the New England Journal of Medicine and one just released in the Journal of the American Medical Association last week found no benefit for patients who took fluvoxamine. In both studies, most of the participants were vaccinated—and even when just looking at unvaccinated patients (in the appendix of the NEJM study, page 14; and the JAMA one, page 18), it looks like the drug failed to work).

Why did fluvoxamine not work out? An editorial in JAMA outlines several possible explanations. But what’s important here is that the scientific process works (sometimes). A researcher had a good idea. Good trials were designed and implemented. After an auspicious start, the end results were disappointing. That’s just how it goes.

Are we done with repurposed therapeutics for Covid-19? No. In fact, increasingly metformin, a diabetes drug, shows glimmers of hope, both for acute and Long Covid. I’ve spoken to researchers who are optimistic. Some commentators—including some like me who are not easily convinced on things of this nature—also see reasons for hope.

But that won’t suffice. Optimism is a nice place to start. Ironclad data from high-quality clinical studies is the destination.