Low Dose Naltrexone

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Please use your clinical judgement and note that this is not necessarily standard practice in NZ.

Naltrexone is an opioid receptor antagonist. However, at low doses (typically 1-5 mg daily, often 4.5 mg), it appears to exert distinct effects relevant to central sensitisation.

Mechanism

The primary proposed mechanism at these low doses is modulation of glial cell activity, particularly microglia, via antagonism of Toll-like receptor 4 (TLR4). Activation of TLR4 on microglia contributes to neuroinflammation and pain facilitation; blocking this receptor with LDN is thought to reduce the release of pro-inflammatory mediators. A secondary, "paradoxical" mechanism proposed involves the transient blockade of opioid receptors (particularly delta and possibly mu) leading to a compensatory upregulation of endogenous opioid peptides (like endorphins) and/or opioid receptors, potentially enhancing endogenous pain control systems over time. Thus, LDN may target CS mechanisms involving both neuroinflammation and potential dysregulation of the endogenous opioid system.

Evidence

Some small studies and case series reported meaningful pain reductions and improved fatigue in fibromyalgia patients. However, the first larger RCT (12 weeks of LDN 6 mg in fibromyalgia) did not show a significant benefit over placebo.

Dosing

Start with 0.5-1.5mg at night, titrate every 1-2 weeks up to a maximum of of 4.5mg. Efficacy maximum at 4-6 weeks. Confirm no concurrent opioid use.

In Auckland can get it from Compound Labs or Optimus. Cost is around $90 for three month supply. Some people are sensitive to the filler. Use sucrose or ginger filler instead of cellulose in that instance.

If the patient is able to manage then the cheaper and more adjustable option is you can prescribe the 50mg tablets, get them to dissolve in 100mL of water, making a concentration of 0.5mg/mL, and store in the fridge covered in aluminium foil. Use a syringe to measure doses (0.5mg, titrating up to max of 4.5mg). Warn them that it tastes foul. This can be a useful option when initiating in order to work out the dose needed.

Adverse Effects

LDN is generally reported to be well-tolerated at the low doses used for pain and inflammation. The most commonly reported side effects are vivid dreams, headache, nausea, and insomnia, which are often transient. Unlike higher doses of naltrexone used for addiction, hepatotoxicity is not considered a significant concern with LDN. However, because naltrexone is an opioid antagonist, it must be used with extreme caution or avoided altogether in patients currently taking opioid analgesics, as it can precipitate acute opioid withdrawal symptoms

External Links

https://www1.racgp.org.au/ajgp/2023/april/low-dose-naltrexone-in-the-treatment-of-fibromyalg

https://www.medicinesinformation.co.nz/2023/07/05/naltrexone-oral-liquid-formula/?pos=naltrexone

References

• Patten et al.. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. Pharmacotherapy 2018. 38:382-389. PMID: 29377216. DOI.