The Off-Label Treatment That Helps Many With Fibromyalgia

Medscape Medical News/Features

The Off-Label Treatment That Helps Many With Fibromyalgia

Laurie Tarkan | October 29, 2025

An unlikely, decades-old drug is gaining traction as a promising off-label treatment for fibromyalgia, driven by a handful of studies and a growing number of anecdotal reports.

Low-dose naltrexone (LDN), a medication originally developed to treat substance use disorders, is said to relieve the chronic pain, fatigue, and brain fog associated with the debilitating condition that afflicts millions of Americans but is difficult to treat.

“It helps over 70% of my patients,” said Scott Zashin, MD, a Dallas-based rheumatologist, and fellow of the American College of Rheumatology. “I’d say less than 10% need to stop it because of side effects.”

Used for decades at doses of 50-100 mg to treat opioid and alcohol use disorders, the drug at that high dose binds to opioid receptors, blocking opioids from attaching to the receptors, so people don’t get that feel-good sensation from booze or drugs.

Early researchers found an unexpected result: “We noticed that when people tapered down to lower doses, their pain would also get better,” said Arya Mohabbat, MD, assistant professor at the Mayo Clinic College of Medicine and Science, Rochester, Minnesota.

Today the LDN trend is fueled primarily by success stories rather than large-scale trials.

One of those stories is Dan Kenyon, age 45, who says LDN reduced his pain by more than half. “It has helped even more with brain fog, fatigue, and sleep,” said Kenyon from Iowa, who was diagnosed in his early thirties after years of unexplained muscle soreness and fatigue.

Despite the word-of-mouth buzz, though, many doctors are not aware of it, don’t think there’s enough evidence to prescribe it, or don’t know how to prescribe it because it’s not marketed by pharmaceutical companies. Still others see LDN as a low-risk, low-cost treatment option for fibromyalgia and other chronic pain conditions — and blame lack of pharmaceutical investment for impeding its progress.

“Naltrexone is an old cheap generic medication,” said Mohabbat. “Just because you formulate it to a lower dose, it doesn’t change the patent, and they can’t charge a lot of money for it.”

How Patients in Pain Are Finding LDN
Looking back, Kenyon thinks the pain started when he was about 20. He had a physically demanding job in fire and water damage restoration, and his muscles would ache throughout the day, pain lingering into the next morning. Even after switching to less strenuous work — first running a retail store, then an online screen-printing business — his pain kept getting worse. Soon it was joined by depression and insomnia. “I got to a point where I just couldn’t motivate myself to work anymore, my sales slowed down, and I didn’t care,” Kenyon said.

At age 32, he saw a rheumatologist who diagnosed him with fibromyalgia. He tried gabapentin, but it gave him panic attacks and affected his balance. Weaning off it was so hard he was reluctant to try other medications.

Browsing an online message board, he read success stories of people on LDN. His rheumatologist said he hadn’t heard of naltrexone being used for chronic pain and wasn’t willing to prescribe it. So Kenyon dropped it.

“Things started getting more painful for me last fall, so it sparked my interest in it again,” Kenyon said. On Reddit, he learned how to get it prescribed online, purchased through a compounding pharmacy.

“I was nervous to try it but started with a very low dose and kept bumping it up every 6 or 7 days,” Kenyon said. It took about 3 months to get to 4.5 mg, which is considered an effective dose. It was working: “I have upwards of a 50% reduction in pain.”

Few Studies, Promising Results
Several studies back LDN for fibromyalgia, though most are small.

In 2013, a randomized controlled study of 31 women with fibromyalgia found that LDN offered an average 29% reduction in pain vs 18% for women on a placebo. An analysis of that data found that half the women on LDN were “much improved” or “very much improved” — compared with just 20%-30% of patients who find meaningful improvement on current fibromyalgia-approved medications, said study author Jarred Younger, PhD, director of the Neuroinflammation, Pain and Fatigue Laboratory at The University of Alabama at Birmingham.

A 2023 cohort study of LDN for pain conditions included 115 people, most having fibromyalgia. The study found that 65% reported a benefit in their pain and other symptoms. A review of nine studies found LDN effective in managing fibromyalgia symptoms, and so did a 2024 review of randomized controlled trials.

Further research shows pain improvements in other conditions, like Crohn’s disease and Long COVID.

To be sure, more research is needed. “We need a double blinded randomized trial for 12 months that looks at side effects and how people do functionally,” said Mohabbat.

“There’s still that question mark in the air,” said Younger. “Clearly it helps a lot of people, but without the study, a lot of physicians aren’t going to want to use it,” he said. But the buzz is growing. “LDN comes up in every medical conference.”

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