Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study

Abstract

Objective: Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial, we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia.

Design: Participants completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks).

Patients: Ten women meeting criteria for fibromyalgia and not taking an opioid medication.

Interventions: Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation.

Outcome measures: Participants completed reports of symptom severity everyday, using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity.

Results: Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone.

Conclusions: We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.

Figures

Figure 1

Overall, self-reported, daily fibromyalgia symptoms (scale 0–100, with 100 being most severe) as a function of placebo and low-dose naltrexone administration. Sections are: baseline, placebo, drug, and washout. A 3-day smoothing has been applied. (A) Data from all participants (N = 10). (B) Data separated by drug responders (30% or greater reduction of symptoms over placebo; solid line, N = 6) and nonresponders (broken line, N = 4).

Figure 2

Changes in pain threshold at laboratory sessions during baseline (visits 1 and 2), placebo (visit 3), drug (visits 4–7), and washout (visit 8) phases. (A) Mechanical pain threshold; baseline is 1.02 kg/cm2. (B) Thermal pain threshold; baseline is 37.9°C.

Figure 3

Relationship between drug response (reduction of fibromyalgia symptoms in the drug condition) and baseline erythrocyte sedimentation rate.