STANFORD, California—Low doses of the opioid receptor antagonist naltrexone, which has been used for decades to treat opioid addiction, might provide a completely new approach to treating fibromyalgia, according to a pilot study by Jarred Younger, PhD, and Sean Mackey, MD, PhD, published online April 17 in Pain Medicine.

"These changes were beyond what I have traditionally seen in clinical practice using more traditional therapies for fibromyalgia.”—Sean Mackey, MD, PhD
"The treatment response was pleasantly surprising, particularly the magnitude of response in some of the individuals. There were women who had been refractory to other therapies and demonstrated a significant improvement in pain symptoms and quality of life. These changes were beyond what I have traditionally seen in clinical practice using more traditional therapies for fibromyalgia,” Dr. Mackey told MSKReport.com.

This pilot proof-of-principle study enrolled 10 women who met diagnostic criteria for fibromyalgia and who were not taking opioids. The participants were given a handheld computer to record their pain, fatigue, and other symptoms on a daily basis. Subjects in this single-blind, crossover trial filled out the daily report for 2 weeks before receiving capsules, then had 2 weeks of placebo, 8 weeks of low-dose naltrexone (4.5 mg/day), and 2 weeks of washout.

Pilot results with naltrexone for fibromalgia justify larger trials

“We were very encouraged by the results,” Dr. Mackey said. “In 6 out of 10 participants, low-dose naltrexone was significantly better than placebo at reducing fibromyalgia symptoms. Low-dose naltrexone reduced daily pain, the highest level of pain, fatigue, and stress. Other symptoms, such as sleep problems, gastrointestinal complaints, and headaches, also seemed to be helped.” Dr. Mackey is Associate Professor and Chief, Pain Management Division, Stanford University School of Medicine, Stanford, California.
 
The investigators did not observe any serious side effects during the course of the study. The most commonly reported side effect (reported by 2 participants) was more vivid dreams. All of the participants who started the study finished the entire 14-week protocol.

Dr. Mackey said that this study provides proof-of-principle that low doses of naltrexone can produce significant reductions in pain in some FM patients but cautions that larger trials are needed to prove efficacy and tolerability over long periods of time.

Naltrexone responses mainly in fibromyalgia patients with elevated ESR

In addition to antagonizing opioid receptors on neurons, naltrexone also inhibits microglia activity in the central nervous system. The researchers suspect that low-dose naltrexone may inhibit microglia activity and thus reverse central and peripheral inflammation.

“Baseline erythrocyte sedimentation rate (ESR) predicted over 90% of variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone,” the authors write. They suggest that ESR may be most useful in defining a subgroup of fibromyalgia patients with low-level systemic inflammation likely to respond to low-dose naltrexone.

ESR is a relatively nonspecific indicator of inflammation. and Dr. Mackey said that his group is currently  investigating more specific biomarkers in an ongoing double-blind study of naltrexone.

Naltrexone for fibromyalgia: Translating research into practice

“This study should not be interpreted to suggest that low-dose naltrexone is a well-accepted treatment for fibromyalgia pain and fatigue. Although we are pleased with the results of this pilot trial, it is still too early to say how effective low-dose naltrexone will be for individuals not in this study,” Dr. Mackey said.

The Stanford researchers are currently enrolling fibromyalgia patients for a double-blind trial of naltrexone, which is scheduled for completion by the end of 2009. Individuals with fibromyalgia who are close to Stanford University can participate in the trial. More information can be found at: http://snapl.stanford.edu/ldn/.

Dr. Mackey added, “We were fortunate to have a number of donors that supported this work. Because naltrexone is a generic drug, it is difficult to secure funds to test the drug. We received critical financial support from a gift given by Jim and Connie Binns. We also received financial and logistical support from the American Fibromyalgia Syndrome Association (AFSA), a not-for-profit organization that specializes in funding studies of fibromyalgia treatments. The Oxnard Foundation provided additional support for the study.”

Reference
1. Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: A pilot study. Pain Medicine. 2009; [epub ahead of print April 17, 2009]