Nightsong
Senior Member (Voting Rights)
Poster abstract from the EULAR rheumatology conference -
EFFICACY OF LOW-DOSE NALTREXONE FOR FIBROMYALGIA: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL WITH 12 MONTHS OF FOLLOW-UP (Luciano et al., 2026)
Low-Dose Naltrexone Fails to Outperform Placebo for Pain in Fibromyalgia Treatment Trial (Medscape News, 6 June 2026)
Abstract
Background: Fibromyalgia (FM) is a chronic primary pain syndrome characterised by widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive difficulties, and emotional distress. It affects approximately 2.7% of the global population, predominantly women, and represents a major cause of disability, healthcare burden, and reduced quality of life. Early small-scale cross-over studies suggested that low-dose naltrexone (LDN) may reduce pain intensity and symptom severity, improve mood and stress, and increase pain thresholds, with a favourable safety profile [3]. However, a recent randomised controlled trial reported no significant effects on pain severity or functional outcomes [2]. Overall, although LDN appears well tolerated, its clinical efficacy in FM—particularly in the long term—remains uncertain, highlighting the need for larger randomised controlled trials with extended follow-up.
Objectives: The main objective was to conduct a double-blind, randomised, placebo-controlled trial comparing a 12-month treatment with LDN 4.5 mg versus placebo on average pain intensity in Spanish women with fibromyalgia. Secondary outcomes included functional impairment, anxiety, depression, perceived stress, cognitive impairment, disability, pathological worry, patient global impression of change, and adverse events. As a secondary objective, we explored whether participants’ beliefs regarding treatment allocation were associated with clinical outcomes. To this end, at the end of the trial, participants were asked whether they believed they had received LDN or placebo.
Methods: We conducted a single-centre, 12-month, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of LDN in Spanish women with FM recruited at Parc Sanitari Sant Joan de Déu (Sant Boi de Llobregat, Spain). Participants, investigators, outcome assessors, and statistical analysts were blinded to treatment allocation. The primary outcome was the change in pain intensity over the previous 7 days, measured using an 11-point numeric rating scale, from baseline to 3 months in the intention-to-treat population. Secondary outcomes included functional impairment, anxiety, depression, perceived stress, cognitive dysfunction, disability, pathological worry, and global impression of change, assessed at 6- and 12-month follow-up visits. Safety was evaluated throughout the study by systematic monitoring of adverse events. The trial was registered with ClinicalTrials.gov (NCT04739995) and EudraCT (2021-002534-16). The study protocol was published by Colomer-Carbonell et al [1].
Results: Between June 2022 and October 2023, 217 participants were screened for eligibility. Ninety-six patients were enrolled and randomly assigned to LDN (n= 47) or placebo (n= 49). Sixty-two participants (64.6%) completed all scheduled follow-up visits (Figure 1). At 3 months, mean pain intensity showed a small reduction in both groups (LDN: −0.33; placebo: −0.64), with no statistically significant between-group difference (p= 0.236). Secondary outcomes demonstrated minor and inconsistent changes across follow-up assessments, without clinically meaningful effects, and responder rates were low and comparable between groups (p= 0.219–0.954). Exploratory analyses suggested that participants who believed they had received LDN reported improvements in certain outcomes; however, these effects were inconsistent. Treatment adherence was high in both groups (LDN: 87%; placebo: 84%). Adverse events were mostly mild and transient, occurring in 33 participants (68.8%) in the LDN group and 36 participants (72.0%) in the placebo group, with no treatment-related serious adverse events reported.
Conclusions: In the present trial, LDN 4.5 mg was well tolerated but did not provide clinically meaningful benefit over placebo in reducing pain intensity or improving functional, psychological, or cognitive outcomes in women with FM. Improvements observed in both groups were small, inconsistent, and not clinically relevant. Exploratory analyses suggested that perceived treatment allocation may have influenced self-reported outcomes, highlighting the potential role of expectancy and attributional effects. Overall, our findings do not support LDN as an effective treatment for FM and underscore the need for alternative therapeutic strategies.
EFFICACY OF LOW-DOSE NALTREXONE FOR FIBROMYALGIA: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL WITH 12 MONTHS OF FOLLOW-UP (Luciano et al., 2026)
Low-Dose Naltrexone Fails to Outperform Placebo for Pain in Fibromyalgia Treatment Trial (Medscape News, 6 June 2026)
Abstract
Background: Fibromyalgia (FM) is a chronic primary pain syndrome characterised by widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive difficulties, and emotional distress. It affects approximately 2.7% of the global population, predominantly women, and represents a major cause of disability, healthcare burden, and reduced quality of life. Early small-scale cross-over studies suggested that low-dose naltrexone (LDN) may reduce pain intensity and symptom severity, improve mood and stress, and increase pain thresholds, with a favourable safety profile [3]. However, a recent randomised controlled trial reported no significant effects on pain severity or functional outcomes [2]. Overall, although LDN appears well tolerated, its clinical efficacy in FM—particularly in the long term—remains uncertain, highlighting the need for larger randomised controlled trials with extended follow-up.
Objectives: The main objective was to conduct a double-blind, randomised, placebo-controlled trial comparing a 12-month treatment with LDN 4.5 mg versus placebo on average pain intensity in Spanish women with fibromyalgia. Secondary outcomes included functional impairment, anxiety, depression, perceived stress, cognitive impairment, disability, pathological worry, patient global impression of change, and adverse events. As a secondary objective, we explored whether participants’ beliefs regarding treatment allocation were associated with clinical outcomes. To this end, at the end of the trial, participants were asked whether they believed they had received LDN or placebo.
Methods: We conducted a single-centre, 12-month, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of LDN in Spanish women with FM recruited at Parc Sanitari Sant Joan de Déu (Sant Boi de Llobregat, Spain). Participants, investigators, outcome assessors, and statistical analysts were blinded to treatment allocation. The primary outcome was the change in pain intensity over the previous 7 days, measured using an 11-point numeric rating scale, from baseline to 3 months in the intention-to-treat population. Secondary outcomes included functional impairment, anxiety, depression, perceived stress, cognitive dysfunction, disability, pathological worry, and global impression of change, assessed at 6- and 12-month follow-up visits. Safety was evaluated throughout the study by systematic monitoring of adverse events. The trial was registered with ClinicalTrials.gov (NCT04739995) and EudraCT (2021-002534-16). The study protocol was published by Colomer-Carbonell et al [1].
Results: Between June 2022 and October 2023, 217 participants were screened for eligibility. Ninety-six patients were enrolled and randomly assigned to LDN (n= 47) or placebo (n= 49). Sixty-two participants (64.6%) completed all scheduled follow-up visits (Figure 1). At 3 months, mean pain intensity showed a small reduction in both groups (LDN: −0.33; placebo: −0.64), with no statistically significant between-group difference (p= 0.236). Secondary outcomes demonstrated minor and inconsistent changes across follow-up assessments, without clinically meaningful effects, and responder rates were low and comparable between groups (p= 0.219–0.954). Exploratory analyses suggested that participants who believed they had received LDN reported improvements in certain outcomes; however, these effects were inconsistent. Treatment adherence was high in both groups (LDN: 87%; placebo: 84%). Adverse events were mostly mild and transient, occurring in 33 participants (68.8%) in the LDN group and 36 participants (72.0%) in the placebo group, with no treatment-related serious adverse events reported.
Conclusions: In the present trial, LDN 4.5 mg was well tolerated but did not provide clinically meaningful benefit over placebo in reducing pain intensity or improving functional, psychological, or cognitive outcomes in women with FM. Improvements observed in both groups were small, inconsistent, and not clinically relevant. Exploratory analyses suggested that perceived treatment allocation may have influenced self-reported outcomes, highlighting the potential role of expectancy and attributional effects. Overall, our findings do not support LDN as an effective treatment for FM and underscore the need for alternative therapeutic strategies.
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