A randomized trial conducted by researchers at Odense University Hospital in Denmark has failed to demonstrate that low-dose naltrexone provides any significant pain relief for patients with fibromyalgia. The trial, which involved 99 patients, found that those assigned to naltrexone reported only a slight decline in pain intensity, with a mean decrease of 1.3 points on an 11-point scale after 12 weeks. In comparison, the placebo group reported a decrease of 0.9 points, and the difference was not statistically significant (P=0.27).
The small difference in pain intensity between the naltrexone and placebo groups, which was not clinically important, was a major disappointment for researchers hoping that the opioid receptor antagonist would provide a better pain relief option for fibromyalgia patients. Even if the 0.4-point difference had achieved statistical significance, it would not have had a meaningful impact on patients’ pain levels. The trial’s findings suggest that naltrexone may not be the solution for all fibromyalgia patients.
Although the trial results did not show significant pain relief with naltrexone, there were indications that the drug may have had some positive effects on cognition. Patients in the naltrexone group reported a more significant improvement in memory problems compared to those in the placebo group, with a mean decrease of 1.4 points versus 0.5 points on the 11-point scale (P=0.004). This finding suggests that naltrexone may have potential benefits for cognitive function in fibromyalgia patients, warranting further investigation.
Fibromyalgia is a complex condition characterized by a wide range of symptoms and levels of disability. The lack of clearly defined pathophysiological mechanisms for all patients makes it challenging to find a one-size-fits-all solution. It is important to acknowledge that fibromyalgia is a heterogenous condition, and what may work for one patient may not work for another.
Naltrexone not only acts on the opioid receptors but also has other effects, including blocking Toll-like receptor 4. This receptor is believed to play a role in many of the symptoms experienced by fibromyalgia patients. While low-dose naltrexone has been used off-label for fibromyalgia for many years, the overall enthusiasm for its use in this indication is relatively low. Experts recommend that off-label treatment should not be terminated for patients who have responded positively to low-dose naltrexone. However, they caution against initiating treatment with naltrexone for patients new to low-dose naltrexone therapy until further adequately powered studies are conducted with a focus on specific patient profiles related to inflammation and autoantibodies.
The FINAL trial, organized by Dr. Karin Due Bruun and her colleagues, aimed to provide a rigorous assessment of the efficacy of naltrexone for fibromyalgia. The trial recruited patients from the Odense area who had received diagnoses of fibromyalgia according to the American College of Rheumatology criteria. Participants had to have a baseline pain score of at least 4 on a 10-point scale. They were randomly assigned to receive either naltrexone or placebo for 12 weeks. The dosing of naltrexone started at one pill per day and could be increased to a maximum of four pills per day by week 4. The mean age of the patients was approximately 50, and all were women. The baseline pain score was 6.3 out of 10, and memory problem ratings averaged 5.7 out of 10. In addition to pain intensity and memory, the trial investigated other outcomes such as fatigue, tenderness, sleep quality, anxiety, depression, stiffness, general physical function, and health-related quality of life. However, only the difference in memory improvement was statistically significant, and this finding lost significance when multiple comparisons were taken into account.
While the trial results were disappointing overall, it is important to consider that there may still be a minority of fibromyalgia patients who could experience clinically meaningful improvements with naltrexone. It is possible that small mean group differences can obscure the benefits for individual patients. Further research is needed to better understand which patients may respond positively to naltrexone and under which specific conditions it may be most effective.
The FINAL trial’s findings indicate that low-dose naltrexone does not provide significant pain relief for the majority of fibromyalgia patients. However, it does show promise for improving cognitive function. Fibromyalgia remains a complex condition with no definitive treatment solution. While naltrexone may not be the answer for all patients, it may still benefit a subset of individuals. Further studies are necessary to explore the potential benefits of naltrexone and identify patient profiles that may respond favorably to the treatment.