Is Ivermectin "Bogus" or a "Miracle Drug"?

ivermectin clinical trial
A clinical trial aims to test ivermectin as a potential treatment for COVID-19. In this photo, a vial of the anti-parasitic drug is seen. Luis Robayo/AFP via Getty Images

Andrew Hill knows first-hand what it's like to bring a breakthrough drug to fruition. The pharmacology researcher at the University of Liverpool in the U.K. helped develop antiviral medications for HIV. "You think about helping to save millions of lives," he says. "It was a wonderful feeling."

Last year Hill was also excited about ivermectin, a 40-year-old generic drug that showed in early laboratory experiments to inhibit the reproduction of SARS-CoV-2, the virus that causes COVID-19. Since ivermectin was already being produced in industrial quantities as a treatment for parasites in people and animals, it could potentially provide an instant lifeline to thousands of COVID-19 patients struggling for breath in emergency rooms around the world—but only if it proved effective in the clinic, not just in a petri dish.

Some of the early, promising studies were found to be flawed; one clinical trial was halted when the drug showed no benefit. Hill reported that the drug didn't seem to be living up to its early promise.

The reluctance of Hill and other scientists, doctors and regulators to endorse ivermectin as a COVID-19 treatment has since inflamed the political right in the U.S. Conservative pundits have called it a "miracle drug," and even some prominent Republican members of Congress fume that medical experts are in cahoots with Big Pharma to protect their profits from vaccines and other treatments. Kentucky Senator Rand Paul has claimed that liberals downplay ivermectin because they are "deranged" by hate for former president Donald Trump.

The reaction on the political left has been nearly as hyperbolic. The steady rap on ivermectin is that it is a dangerous, fake COVID-19 treatment pursued only by science-denying, vaccine-dodging crackpots. Or as the Los Angeles Times put it in one headline, the drug is a "bogus COVID treatment" and "a darling of conspiracy-mongers." "That seems to reflect some media bias based on the fact that it's mostly Trump supporters who are taking it," says David Boulware, an infectious disease physician and researcher at the University of Minnesota, and one of the directors of a major effort to conduct trials of potential COVID-19 treatments, including ivermectin.

Like so many things these days, separating science from politics is exceedingly difficult—especially when the science keeps evolving, and scientists argue among themselves with the public and politicians looking over their shoulders. To be sure, the science seems clear that for prevention of serious COVID-19-related illness, vaccination is the only measure proven to be safe and effective. The U.S. Food & Drug Administration has not approved ivermectin for any COVID-19-related purpose, and the FDA, the Centers for Disease Control and Prevention, and most major medical and pharmaceutical associations in the U.S. have warned that taking the drug in large doses can pose serious risks to health.

Even so, the lack of sufficient data so far from large randomized trials currently underway leaves just enough scientific uncertainty to keep the battle over ivermectin—fueled by distortions and selective reporting on both sides—raging. "The book isn't closed yet,"says Boulware. "It's become a political issue, but we need more data to really know if it works or not."

Based on the data so far, most scientists currently expect ivermectin to follow hydroxychloroquine—another generic drug hyped by conservatives, including Trump himself, as a miracle COVID-19 treatment—into the dustbin of dubious medical claims. But that won't put an end to a larger, politically charged debate over whether or not ordinary Americans should call the shots on drugs, even when unproven. The argument has been playing out since before the birth of America, but it's become supercharged during the pandemic.

Not Just a Horse Dewormer

The mainstream media has, by and large, portrayed ivermectin as a livestock dewormer and the notion that the drug might help fight COVID-19 as sheer nonsense. But that narrative ignores a much more interesting background to the drug.

It's true that most of the $1 billion dollars a year in revenue that ivermectin once brought Merck, the pharmaceutical company that developed it, came from its use on cows, horses and other farm animals. But ivermectin has also been a critical, widely prescribed anti-parasitic drug for humans. It has been used to virtually wipe out elephantiasis, river blindness and other devastating illnesses in some parts of the world. It's the best treatment in the U.S. for head lice and scabies. Indeed, the 2015 Nobel Prize in medicine went to the scientists whose breakthroughs led to the drug.

While ivermectin isn't generally considered an antiviral drug, studies published early in the pandemic demonstrated that at high concentrations it keeps SARS-CoV-2 from replicating in cell cultures. Early studies in human patients appeared to show the drug might in fact be a potent and inexpensive treatment for COVID-19. In typical human doses, side effects are minimal. "There are decades of safety data behind its use in approved doses for anti-parasitic indications," says Michael Ganio, who heads pharmacy practice and quality efforts at the American Society of Health-System Pharmacists.

The notion that these preliminary studies sent conservative anti-vaxxers rushing to veterinary supply stores to buy and chug horse dewormer is also a distortion, adds Ganio. In fact, the big push from would-be ivermectin-takers has been to try to get prescriptions for the drug from doctors, who can legitimately issue them on an "off-label" basis, meaning for uses other than the ones for which they are officially FDA-approved. Pharmacies can turn prescriptions down if there's concern over safety, "but they rarely flat-out refuse to fill one," notes Ganio. "There are some prescribers and pharmacists who believe in ivermectin as a COVID-19 treatment, and they've been perfectly willing to prescribe and fill it." In one week in August, according to the CDC, retail pharmacies filled 88,000 ivermectin prescriptions, about 25 times the 2019 weekly average.

The headlines have largely ignored the nuances of the ivermectin controversy, repeatedly blaring references to horse dewormers and "quack or "bogus" treatments, terms used to describe ivermectin in headlines by The Economist, The Seattle Times, Time and Forbes, among many others. "It's not a miracle cure, but it's inflammatory to denigrate it that way," says the University of Minnesota's Boulware.

But if the media has been exaggerating the folly of taking ivermectin for COVID-19, the political right has plunged into perpetrating its own false narratives about the drug. Spurred on by those first studies, support for the drug as a COVID-19 treatment started building throughout 2020 in conservative circles via social media. But ivermectin boosterism really took off early this year when Fox News star Laura Ingraham began singing its praises on the air, after which celebrity podcaster Joe Rogan started talking it up, supposedly taking it to treat his own case of COVID-19.

When clinicians, scientists and regulators objected that much more data was needed to justify embracing the drug, Rand Paul reportedly told attendees at a Kentucky Town Hall that researchers were purposely turning their backs on ivermectin because of its association with Trump support. In fact, the drug was already being widely studied. (Paul later claimed his position had been misrepresented.)

Senator Rand Paul
Senator Rand Paul (R-Kentucky) told constituents on Friday that "hatred for Trump" is hindering research into Ivermectin as a COVID-19 treatment. In this photo, Paul departs from the Senate Chambers in the U.S. Capitol on July 21 in Washington, D.C. Anna Moneymaker/Getty Images

That stance, and similar comments from other popular conservatives, reinforced the claim that the government and healthcare industries were more interested in protecting the pharmaceutical industry's vaccine profits than treating COVID-19. "That's a bunch of nonsense," says Boulware. "The government is funding the new ivermectin trials—the sort of funding Senator Paul usually votes against." Among the large U.S. nation-wide trials currently looking at ivermectin are the ACTIV-6 trial led by Duke University, which is enrolling 15,000 patients, and the 1,200-patient COVID-OUT trial led by Boulware and colleagues at the University of Minnesota.

Overdosing

As regulatory agencies and leading clinical organizations like the American Medical Association started taking strong stands earlier this year against taking ivermectin for COVID-19 in the absence of clearer data, prescriptions became harder to come by. That's when hard-core fans of the treatment started turning to veterinary supply stores, where the drug can be bought over the counter.

That development introduced far more risk into the ivermectin fad, because livestock versions are typically highly concentrated to match the greater weight of horses and cows, resulting in doses as much as 15 greater than the maximum dose considered safe for humans. Known side-effects of even mild ivermectin overdosing include nausea, muscle pain and diarrhea, and it's downhill from there in larger doses.

Though national figures on ivermectin overdoses aren't readily available, both the CDC and FDA say they are receiving a stream of reports of people becoming severely ill from ivermectin overdoses. A poison center in Portland, Oregon reported five cases of ivermectin overdoses requiring hospitalization in August, two of which required intensive care. The American Association of Poison Control Centers says ivermectin-related calls increased five-fold in August, when demand for the drug seems to have skyrocketed.

What COVID-19-related benefits can ivermectin self-treaters hope to get against these potentially serious risks? Probably little or none. The earliest batch of studies, mostly conducted last year and early this year, seemed to show big benefits to patients with severe COVID-19 illness who took the drug. Liverpool University's Hill was among the first to conduct a meta-study of that early data, aggregating information from 11 randomized controlled trials, and finding in a paper published in July that ivermectin reduced the risk of death by 56 percent in those combined trials. But when other researchers reported finding flaws in the data of one of the studies he had included, Hill took a closer look, and found that every one of the positive studies was marred by bogus data or poor study design. "When I excluded the fraud and bias, nothing remained," he says.

Just because the earlier studies didn't hold up doesn't prove ivermectin is a bust. Scientists insist on large studies called randomized controlled trials (RCTs), in which a drug's efficacy is carefully measured against a control group, to settle these questions. In addition to the ACTIV-6 and COVID-OUT trials, the 5,000-patient PRINCIPLE trial in the U.K. led by Oxford University is studying ivermectin. All three should have preliminary results by the end of the year. (A fourth large trial, the TOGETHER study in Canada and Brazil, was studying ivermectin in relatively low doses, but stopped doing so in August when preliminary results showed little benefit.) Another 75 or so smaller ivermectin trials are registered with the National Institutes of Health, promising a wealth of data in the coming year.

Although Hill and Boulware are not optimistic about the chances that ivermectin will prove useful against COVID-19, they both insist it's important to wait until the data is in before ruling it out.

Medical freedom

What the trials almost certainly won't settle is the inclination of large swaths of the public to demand access to unapproved treatments for COVID-19 that are likely ineffective and often dangerous. It's the flip side of the coin to refusing to follow the government's and medical-community's push to get people vaccinated, notes Lewis Grossman, a law and history professor at American University who studies how Americans push back against medical advice and regulation.

Mistrusting government and doctors is part and parcel of a "medical freedom" movement that has run throughout almost all of American history, says Grossman, author of the recent book, Choose Your Medicine: Freedom of Therapeutic Choice in America. The movement may be as strong today as it ever was."Americans have always felt there's some kind of shadowy agreement between government, medicine and big business to stick it to the public," he says. "Part of that is feeling that you can't tell me what medicine I can't take."

The pandemic has intensified the emergence of a particularly strong strain of the medical freedom ideology today—and so has the current political polarization, characterized as it is by conservatives' fear of a liberal "deep state." In fact, Fox's Ingraham is among those Republicans who have referred to a current "medical deep state." That partisan slant has sent medical mistrust into overdrive under COVID-19, says Grossman, helping to drive the hype over a string of failed and sometimes bizarre and dangerous treatments, including convalescent plasma, hydroxychloroquine, ingested bleach and, more recently, inhaled hydrogen peroxide. The movement goes as far back as the Revolutionary War, when most Americans refused to follow the British in being inoculated against smallpox—a stance that allowed the disease to weaken and kill so many American rebels that it almost cost the war in the first year.

Next up on the list of COVID-19 would-be treatments that may not pass medical-science muster but could win wide support anyway is the generic antidepressant fluvoxamine. As with ivermectin, initial studies made the drug's anti-inflammatory action appear promising. One large U.S. trial of the drug was stopped in mid-September when preliminary results proved disappointing. Other trials of the drug are ongoing. Whether medical-freedom advocates pay any attention to the results remains to be seen.

Hill, meanwhile, is not enjoying any of the thrill and acclaim of his earlier work on HIV. Since revising his meta-study in ivermectin to incorporate the recent, disappointing data, he's been getting non-stop abuse. "These ivermectin supporters are insistent, aggressive and abusive," he says. He's gotten death threats with photos of coffins and nooses—all for the crime of following his research.