On the 12th of August, Pain Management Nursing published an article entitled ‘Symptom Response to Low-Dose Naltrexone in Fibromyalgia: An Exploratory Analysis of the Randomized Placebo-Controlled FINAL Trial (Nielsen et al) examined the efficacy of low-dose naltrexone (LDN) on pain in women with Fibromyalgia.
Abstract
Background: Fibromyalgia (FM) remains difficult to manage due to a highly variable symptom profile. The “FINAL” randomized, placebo-controlled trial examined the efficacy of low-dose naltrexone (LDN) on pain in women with FM, showing no significant difference in pain reduction at the group level but potentially higher 30% pain response rates. Analysis of secondary outcomes showed potential improvements in memory problems.
Objectives: This exploratory analysis aimed to further investigate individual responses to LDN treatment by analyzing 30% responder rates for six secondary FM outcomes.
Methods: The FINAL trial included 99 women with FM who were randomized 1:1 to treatment with LDN or placebo for 12 weeks. Based on original data from this trial, 30% response rates were assessed for the six selected secondary outcomes: tenderness, fatigue, sleep disturbances, depression, memory problems, and stiffness. Risk ratios (RR) with 95% confidence intervals (CI) were calculated to assess differences between groups.
Results: No significant differences were found between treatment groups for any of the symptom response categories. The highest RR was observed for memory (RR = 1.67, 95% CI: 0.82-2.95), followed by sleep (RR = 1.28, 95% CI: 0.92-2.64), stiffness (RR = 1.26, 95% CI: 0.84-2.89, p = .47), tenderness (RR = 1.16, 95% CI: 0.88-2.67), fatigue (RR = 1.10, 95% CI: (0.78-3.13) and depression (RR = 0.96, 95% CI: 0.92-2.66).
Conclusions: Response rates for 30% improvement in six selected nonpain outcomes were similar after 12 weeks treatment with LDN or placebo in women with FM. Larger studies investigating 30% response rates are warranted
MEA comment
As we have discussed on many occasions on the ME Association's Facebook page, there is a considerable amount of patient evidence to indicate that LDN (low dose naltrexone) can be of benefit in the management of ME/CFS and several other conditions with overlapping symptoms – fibromyalgia in particular.
A number of clinical trials have now been carried out, or are currently in progress to assess the efficacy and safety of LDN in ME/CFS, Long Covid and in fibromyalgia – including the ME/CFS trial funded by the MEA.
Overall, the results from these trials have been negative or only shown minor benefits and the latest trial to report, which involves people with fibromyalgia, failed to show any significant benefit in pain, fatigue or sleep disturbance reduction although there was some minor improvement in cognitive/memory performance.
As has already been reported, the preliminary negative results from the MEA funded trial that has been carried out by Dr Luis Nacul and colleagues in Canada were discussed at a conference earlier this year and are now being submitted for publication. We will say more about these results when the paper has been published.
So we currently have no sound evidence from a number of clinical trials that LDN is an effective form of treatment for these conditions. And without this type of evidence this is not a treatment that is going to receive approval from NICE for use on the NHS.
Having said that, as the researchers here point out, there is still a good case to look at those who did respond in more detail.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
Further information
- The ME Association: Update: LDN clinical trial: Progress Report July-September 2025 | October 23, 2025
- The ME Association: Leading UK Charity invests in Canadian trial of drug treatment for ME/CFS and Long Covid | April 2, 2025
- The ME Association: Treating Long Covid and Post Covid ME/CFS with LDN | May 20, 2025
- The ME Association: Research: Low-Dose Naltrexone Ineffective for Fibromyalgia | December 11, 2023