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

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.

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.

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.

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.