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

Abstract

Purpose

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

Abbreviations

LDN low-dose naltrexone; MED maximally effective dose; BPI Brief Pain Inventory; PROMIS Patient-Reported Outcomes Measurement Information System; HSD hypermobile spectrum disorder; hEDS hypermobile Ehlers-Danlos syndrome; MCAD mast cell activation disorder.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The study was funded by the primary author, Norman Marcus, MD. Norman Marcus, MD owns the patent to the Noci-Stim. The fee for publishing this paper was paid by a grant from the Ehlers-Danlos Society.