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. 2024 Mar 21:17:1273-1284.
doi: 10.2147/JPR.S451183. eCollection 2024.

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

Norman J Marcus  1   2 , Lexi Robbins  1 , Aya Araki  1 , Edward J Gracely  3   4 , Theoharis C Theoharides  5   6
Affiliations

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

Norman J Marcus et al. J Pain Res. .

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.

Keywords: chronic pain; hypermobile Ehlers Danlos syndrome; low-dose naltrexone; musculoskeletal pain; myalgia; nociplastic pain.

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.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flowchart of Patient Inclusion.
Figure 2
Figure 2
Effectiveness Curve. Diagram used only to discuss possible sequence of events for a patient with an MED around 3.25. Other patients would have different maximum points. This exact symmetrical pattern of response has not been experimentally demonstrated. The area under the curve (AUC) is the window of effectiveness and is the point in the titration that the patient is obliged to carefully observe any response to dose increments. The apogee of the curve is the MED. Moving beyond the MED produces no additional improvement or actually a decrement in improvement.
Figure 3
Figure 3
Histogram of individual MEDs. Individual MEDs for each patient in the study clearly suggesting idiosyncratic doses.
See this image and copyright information in PMC

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