Effective Doses of Low-Dose Naltrexone for Chronic Pain – An Observational Study

Abstract

Norman J Marcus,1,2 Lexi Robbins,1 Aya Araki,1 Edward J Gracely,3,4 Theoharis C Theoharides5,6 1Norman Marcus Pain Institute, New York, NY, USA; 2Department of Anesthesiology and Neurological Surgery, Weill Cornell Medicine, New York, NY, USA; 3Family, Community & Preventative Medicine, Drexel University College of Medicine, Philadelphia, PA, USA; 4School of Public Health, Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA; 5Department of Immunology, Tufts University School of Medicine, Boston, MA, USA; 6Institute for Neuro-Immune Medicine, Nova, Southeaster University, Clearwater, FL, USACorrespondence: Norman J Marcus, Private Practice, Norman Marcus Pain Institute, 30 E. 40th Street, Ste 1100, New York, NY, 10016, USA, Tel [phone], Email [email protected]: Despite the availability of a wide variety of analgesics, many patients with chronic pain often experience suboptimal pain relief in part related to the absence of any medication to address the nociplastic component of common pain syndromes. Low-dose naltrexone has been used for the treatment of chronic pain, typically at 4.5 mg per day, even though it is also noted that effective doses of naltrexone for chronic pain presentations range from 0.1 to 4.5 mg per day. We performed an observational analysis to determine the range of effective naltrexone daily dosing in 41 patients with chronic musculoskeletal pain.Methods: Charts of 385 patients, 115 males, 270 females, ages 18– 92, were reviewed. Two hundred and sixty patients with chronic diffuse, symmetrical pain were prescribed a titrating dose of naltrexone to determine a maximally effective dose established by self-report of 1) reduction of diffuse/generalized and/or severity level of pain and/or 2) positive effects on mood, energy, and mental clarity. Brief Pain Inventory and PROMIS scales were given pre- and post-determining a maximally effective naltrexone dose.Results: Forty-one patients met all criteria for inclusion, successfully attained a maximally effective dose, and completed a pre- and post-outcome questionnaire. Hormesis was demonstrated during the determination of the maximally effective dosing, which varied over a wide range, with statistically significant improvement in BPI.Conclusion: The maximally effective dose of low-dose naltrexone for the treatment of chronic pain is idiosyncratic, suggesting the need for 1) dosage titration to establish a maximally effective dose and 2) the possibility of re-introduction of low-dose naltrexone to patients who had failed initial trials on a fixed dose of naltrexone.Plain language summary: Low-dose naltrexone (LDN) has been used to treat chronic pain. There is, however, no agreed on effective dose, leaving clinicians without guidelines on initiating treatment with naltrexone. It appears that the dose of LDN for any patient is idiosyncratic, and in a small study, ranges from 0.1 to 6.0 mg/day. Understanding the various possible mechanisms of action of LDN may help the clinician to understand how and why it can effectively reduce chronic pain. A titration schedule to establish the maximally effective dose for chronic myofascial pain is presented.Keywords: myalgia, low-dose naltrexone, chronic pain, hypermobile Ehlers Danlos syndrome, nociplastic pain, musculoskeletal pain

Keywords

• myalgia
• low dose naltrexone
• chronic pain
• hypermobile ehlers danlos syndrome
• nociplastic pain
• musculoskeletal pain