A recent randomized trial has revealed that low-dose naltrexone does not provide any additional pain relief compared to a placebo in patients with fibromyalgia. This is a significant setback for the hopes that this opioid receptor antagonist could be an effective treatment for a condition that has thus far been difficult to manage. The trial, which involved 99 patients, found that those assigned to naltrexone experienced a mean decline of 1.3 points in pain intensity after 12 weeks, compared to a decrease of 0.9 points in the placebo group. Although there was a small difference of 0.4 points, it was not statistically significant nor clinically important. However, naltrexone did show promise in improving cognition, specifically memory problems. These findings suggest that further investigation into the effect of naltrexone on cognition is warranted.
Fibromyalgia is a complex condition characterized by a wide range of symptoms and disability levels. It lacks clearly defined pathophysiological mechanisms, which has made finding effective treatments challenging. It is important to note that not all patients will respond to the same treatment, underscoring the need for diverse approaches. Naltrexone, in addition to blocking opioid receptors, has other effects such as blocking Toll-like receptor 4, which is implicated in several fibromyalgia symptoms. While low-dose naltrexone has been used off-label for fibromyalgia for many years, experts caution against initiating treatment with low-dose naltrexone for patients who have not previously used it until more studies with specific patient profiles are conducted. This highlights the need for more research to better understand the potential benefits and limitations of this treatment approach.
The FINAL trial was designed to rigorously assess the effectiveness of naltrexone for fibromyalgia. The study enrolled patients from the Odense area in Denmark who had previously received diagnoses of fibromyalgia according to American College of Rheumatology criteria. The eligibility criteria also included a baseline pain score of at least 4 on a 10-point scale. The participants were randomly assigned to receive either naltrexone or a placebo for 12 weeks. The dosing of naltrexone started at one pill per day and could be increased up to four pills per day by week 4. The mean age of the patients was approximately 50 years, and all participants were women. The baseline pain score was 6.3 out of 10, and the average rating for memory problems was 5.7 out of 10. The study assessed various outcomes including pain intensity, memory problems, fatigue, tenderness, sleep quality, anxiety, depression, stiffness, general physical function, and health-related quality of life.
Insignificant Pain Relief
The trial results revealed that there was no significant difference in pain relief between the naltrexone and placebo groups. The mean decline in pain intensity after 12 weeks was 1.3 points in the naltrexone group and 0.9 points in the placebo group, which was not statistically significant (P=0.27). On an 11-point scale, the difference of 0.4 points was deemed clinically insignificant. Despite these results, approximately one-quarter of the patients in the naltrexone group reported a 50% improvement in pain intensity compared to only 14% in the placebo group. Although this finding is noteworthy, it should be interpreted in the context of the overall trial outcomes. The researchers indicated that the trial may have been underpowered for other outcomes, as it was primarily designed to detect a 1-point difference in pain intensity.
While naltrexone did not provide significant pain relief, it demonstrated potential benefits for cognition. Patients in the naltrexone group reported a significantly greater improvement in memory problems compared to the placebo group. The improvement was evident when ratings of memory problems were compared using an 11-point scale. The difference between the naltrexone group (-1.4 points) and the placebo group (-0.5 points) was deemed statistically significant (P=0.004). This finding suggests that naltrexone may have a positive impact on cognitive function in fibromyalgia patients. Given this result, further investigation into the effect of naltrexone on cognition is recommended.
Considerations and Recommendations
It is important to consider that some fibromyalgia patients may still benefit from naltrexone despite the overall trial findings. The researchers emphasized that there is a risk of individual patient improvements being overshadowed by small mean group differences. Therefore, it is crucial to tailor treatments to individual patients and their specific needs. While the use of low-dose naltrexone for patients who have previously responded to it can be continued, initiating treatment with naltrexone for patients new to this approach is not recommended at this time. Instead, additional adequately powered studies should be conducted to understand the potential benefits of naltrexone in fibromyalgia patients with distinctive inflammatory and autoantibody profiles. These studies could shed light on the role of inflammation and autoimmunity in fibromyalgia, ultimately leading to more targeted and effective treatment options for patients.