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What do the drugs hydroxychloroquine, ivermectin, colchicine, metformin, lopinavir/ritonavir, azithromycin, interferon-B, and even remdesivir have in common? All of these previously existing medications—and many others—have been proposed as possible treatments for Covid-19, with varying degrees of hype. Unfortunately, hopes aside, none of them have been shown to stop disease progression in any high-quality clinical trials. Now, an existing drug finally has been found to help. And despite an early but much smaller trial that also showed reasons for hope, the drug not on most peoples’ radars. After today, that should change.
The idea of repurposing old drugs for Covid-19 has tremendous appeal. If any existing medications were to help, they would likely be inexpensive, widely available, and would come with well-established records on their safety and any side effects. But time after time, hopes have been dashed, especially when it comes to the search for an existing drug that can stop Covid-19 early in its course.
Fluvoxamine, an antidepressant and obsessive-compulsive disorder drug that has been around for decades, appears to accomplish what we hoped these other drugs might—which is to actually do something to help Covid-19 patients from getting worse before it’s too late. In fact, a new study appearing in Lancet Global Health shows that among patients with Covid-19 symptoms (and confirmed infections) for 1 week or less, and at least one risk factor for serious disease, those receiving fluvoxamine twice per day for 10 days were substantially less likely to require hospitalization (either to an observation unit for more than 6 hours, or to a full medical unit). Around 11% of patients who were randomly selected to take fluvoxamine required hospitalization versus 16% among those who received a placebo. That means for every 20 Covid-19 patients deemed to be at high risk for a progressing to a serious case, receiving fluvoxamine prevented 1 hospitalization. Among patients who had received fluvoxamine for longer than a day, the numbers were even better.
Does this mean that other similar antidepressants might also work against Covid-19? It’s possible but unknown. Even among drugs that are in the same class as fluvoxamine, which is a selective serotonin re-uptake inhibitor (SSRI), it’s likely that some may have a helpful effect while others won’t. That’s because researchers believe that the reason the drug might help Covid-19 patients has nothing to do with its chemical properties that treat depression. Instead, it is believed that the drug’s anti-inflammatory properties may be the key. Some SSRIs have similar anti-inflammatory properties, and others do not. None of them have been rigorously tested, as fluvoxamine now has. In addition, as with any medication, side effects are possible. In fact, fluvoxamine itself comes with side effects like nausea that makes it difficult for some patients to take the drug. That was reflected in this latest trial. On one hand, around 26% of those who received fluvoxamine took fewer than 80% of the doses, compared with around 18% in the placebo group. Even that difference of 6% tells us something. So, if you happen to become infected with coronavirus, please don’t start popping SSRIs you might have lying around the house. Many of these drugs may do nothing to help Covid-19 and could just make you feel worse. However, based on these new data, it’s reasonable to ask your doctor about fluvoxamine if you become infected and I suspect many Covid-19 treatment protocols will soon be amended to include it.
The story of fluvoxamine fascinates me. Why, among all the existing drugs proposed for repurposing did this one work? Dr. Angela Reiersen, a psychiatrist at Washington University School of Medicine, had been studying an unrelated medical condition that fluvoxamine might possibly treat. When Dr. Reiersen came down with a mild case Covid-19 early in the pandemic, she realized that the anti-inflammatory properties of the medication could help. She reached out to experts in clinical research and studies slowly began to take shape. But Reiersen herself never took fluvoxamine while she was infected and recovering from her bout with Covid-19. She wisely understood the difference between a good idea and a rigorously tested one. Too often we lionize the “brave” doctor who believed in a treatment so much that they tested it on themselves. Such endeavors have Hollywood appeal, but actually amount to anecdotes whose meaning can’t be interpreted. That’s why large well-conducted studies are necessary. If Dr. Reiersen came down with Covid-19 today, though, she would take the medication. And so would I (albeit, the usefulness of fluvoxamine among people who are vaccinated against Covid-19 is not apparent and was not directly assessed in this new study).
Fluvoxamine is the first pill for which we now have high-quality clinical data to support use in preventing early Covid-19 progression. (An inhaled steroid called budesonide has also been shown to decrease the number of patients who need urgent treatment early in the course). While Merck’s new medication molnupiravir appears poised to have a similar use, clinical trial data are not yet available. In addition, fluvoxamine may cost as little as $4, though prices may be higher in some areas. But even at under $30, the medication will be far more affordable than molnupiravir, which could cost as much as $700. Meanwhile, another study out today in the New England Journal of Medicine found that an intravenous medication called sotrovimab also appears to decrease Covid-19 disease progression. But at more than $2,000 for the one-time dose, it would take over $30,000 of the medication to prevent a single hospitalization. Meanwhile, for patients similar to those who participated in the fluvoxamine trial, the financial investment needed to prevent one hospitalization could be as low as $80. Given that half of the world’s population remains unvaccinated, inexpensive pills (rather than expensive intravenous treatments that can only be administered in specialized medical settings) have a real chance to help a significant number of people. That’s why today’s news is cause for celebration.
Going forward, how can we distinguish which medications work against Covid-19? One important answer is to check to see if a new study came from a large, well-established, transparent research group doing genuinely randomized clinical trials. There are now a handful of such research collaborations around the world (listed below) doing important research. These massive efforts have already provided helpful answers during the Covid-19 pandemic. Just as important as discovering which medications actually help (such as dexamethasone for Covid-19 patients with low oxygen levels, along with a small number of other treatments), the results of these studies also help us discard ideas that were hoped to have worked, but which just didn’t. This protects patients by minimizing exposure to drugs that they don’t need—and reducing false hope that may lead to risky behaviors stemming from overconfidence.
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