Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.
High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.
But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.
Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID. Antivirals are also on the list.
Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).
Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said.
“It was super scary as a provider to start doing that, but my patients were suffering so much,” she said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.
Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID.
The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.
Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.
The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice.
“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain.
Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.
No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook.
A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)
Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.
Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.
Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments.
Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.
“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.
In some cases, the drugs are backed by small studies, he said.
“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.
Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.
But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.
“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.
The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.
“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.
Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.
As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary.
“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”
He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse.
Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments.
“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”
Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing.
“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”
Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.
“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
A version of this article appeared on Medscape.com.