Patients suffering from fibromyalgia were hopeful that low-dose naltrexone, an opioid receptor antagonist, would provide them with much-needed pain relief. However, a recent randomized trial dashed those hopes. According to Dr. Karin Due Bruun and colleagues from Odense University Hospital in Denmark, the trial showed that patients assigned to naltrexone experienced a mean decline in pain intensity of only 1.3 points after 12 weeks, compared to a decrease of 0.9 points in the placebo group. This difference was not statistically significant (P=0.27) and would not have been considered clinically important even if it had achieved significance.
While low-dose naltrexone did not provide significant pain relief, it did show signs of improving cognition in fibromyalgia patients. The study found that patients’ ratings of memory problems improved significantly more in the naltrexone group compared to the placebo group (-1.4 vs -0.5 points on the 11-point scale, P=0.004). This suggests that naltrexone may have some benefit in terms of cognitive function for individuals with fibromyalgia. The researchers recommend further investigation into this potential benefit in future trials.
It is important to note that some patients in the trial may have experienced clinically meaningful improvements in pain relief with naltrexone, despite the lack of significant group differences. This highlights the heterogeneity of fibromyalgia, with varying symptoms and disability levels among patients. Winfried Häuser, MD, of Technische Universität in Munich, and Mary-Ann Fitzcharles, MD, of McGill University in Montreal, emphasized the lack of a one-size-fits-all solution for fibromyalgia treatment. While naltrexone may not be recommended for all fibromyalgia patients, it should not be abruptly terminated for those who have found relief with the medication.
Naltrexone works by preventing the activation of μ-opioid receptors, but it also has other effects, such as blocking Toll-like receptor 4. This receptor is believed to play a role in many of fibromyalgia’s diverse symptoms. The potential for naltrexone to target these mechanisms led to its off-label use in fibromyalgia treatment for many years. However, given the disappointing results of the recent trial, Häuser and Fitzcharles caution against initiating naltrexone treatment in fibromyalgia-naive patients. They suggest waiting for results from additional well-powered studies with distinct patient profiles, particularly those focusing on inflammatory and autoantibody markers.
The trial conducted by Dr. Due Bruun and colleagues, known as FINAL, aimed to provide a rigorous evaluation of the efficacy of naltrexone for fibromyalgia. The study recruited patients from the Odense area who had received fibromyalgia diagnoses based on American College of Rheumatology criteria. Participants had to have a baseline pain score of at least 4 on a 10-point scale. The patients were randomly assigned to receive either naltrexone or placebo for 12 weeks. The initial dose was one 1.5-mg pill per day, which could be increased up to four pills per day by week 4. The dosing was then stabilized at the highest tolerated level. The study included various outcome measures, including pain intensity, memory problems, fatigue, tenderness, sleep quality, anxiety, depression, stiffness, general physical function, and health-related quality of life. However, apart from memory, none of the other outcomes showed significant differences between the naltrexone and placebo groups. Häuser and Fitzcharles observed that the significant difference in memory scores no longer remained significant after correcting for multiple comparisons.
Dr. Due Bruun and colleagues acknowledge that the trial may have been underpowered to detect differences in outcomes other than pain intensity. The trial was primarily powered to detect a 1-point difference in pain intensity. Therefore, it is possible that naltrexone might have shown some meaningful effects on other symptoms or functional measures if the trial had been designed and powered differently.
The recent randomized trial of low-dose naltrexone for fibromyalgia pain relief yielded disappointing results. The medication did not provide significantly greater pain relief compared to placebo. However, it did show potential benefit in terms of cognitive function. The heterogeneity of fibromyalgia and the lack of clearly defined pathophysiological mechanisms make it challenging to find a one-size-fits-all treatment solution. Despite the lack of overall efficacy, a subset of patients may still benefit from naltrexone treatment. Further research is necessary to determine the specific patient profiles and inflammatory markers that may influence treatment response.
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