Presented at the 2012 AAPM Annual Meeting « Back

Low-Dose Naltrexone Reduces the Symptoms of Fibromyalgia: A Double-Blind and Placebo-Controlled Crossover Study

Jarred Younger, PhD, jyounger@stanford.edu¹, Rebecca McCue, BA¹, Noorulain Noor, BS², Sean Mackey, MD PhD², (1) Stanford University School of Medicine, Palo Alto, California, (2) Stanford University, Palo Alto, California

Introduction/Statement of the Problem: Fibromyalgia is a common chronic pain disorder that is characterized by diffuse musculoskeletal pain, sensitivity to mechanical stimulation, and profound fatigue. We demonstrated in a previous pilot study that low dosages of naltrexone (LDN), taken at 4.5 mg daily, reduced pain and fatigue in ten women with fibromyalgia (1). Because the earlier study was limited by its single-blind design, we conducted this study, which is the first placebo-controlled, double-blind trial of a glial cell modulator for treating chronic pain. Materials and Methods: Naltrexone is an orally available opioid antagonist that has also been demonstrated to suppress the release of proinflammatory factors from microglia, via antagonistic effects on toll-like receptor 4 (2). In this study, 30 women completed a protocol involving 2 weeks of baseline, 12 weeks of LDN, 4 weeks placebo (counter-balanced), and 4 weeks follow-up. Each day, participants completed symptom severity reports via a handheld computer. The primary outcome was daily pain. All participants provided informed consent, and all procedures were approved by the Institutional Review Board at Stanford University School of Medicine. Results: Pain was reduced significantly more in the LDN condition (43%) versus the placebo condition (33%). Participants rated LDN as tolerable as placebo (89.2 versus 89.4, respectively, rated on a 100-point scale). The only side effects reported more often in LDN than placebo were vivid dreams (37% versus 13%) and headache (16% versus 3%). Conclusions: While further randomized controlled trials are needed, LDN may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia. References: 1)Younger J, Mackey S (2009). Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Medicine. 10, 663-672 2)Hutchinson et al., (2008). Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). European Journal of Neuroscience. 28, 20-29

Funding: American Fibromyalgia Syndrome Association