What are the guidelines for low-dose Naltrexone (opioid receptor antagonist) therapy?

From the Guidelines

Low dose naltrexone (LDN) should be prescribed at a starting dose of 1.5 mg at bedtime, with a gradual bi-weekly increase of 1.5 mg to a final maximum dose of 4.5 mg taken at bedtime, as this regimen has been shown to be effective in managing chronic neuropathic pain, including fibromyalgia, complex regional pain syndrome, low-back pain, and painful diabetic neuropathy 1. The medication works by acting as an opioid antagonist for the μ-opioid and κ-opioid receptors, as well as an antagonist to toll-like receptor 4, which has been linked to neuropathic pain, reducing the release of pro-inflammatory cytokines and modulating microglial activity. Some key points to consider when prescribing LDN include:

• Starting with a low dose of 1.5 mg daily to minimize side effects, such as headache, tachycardia, and vivid dreams
• Gradually increasing the dose every 1-2 weeks to allow the patient to adjust to the medication
• Taking the medication consistently at the same time each day, preferably at night, to maintain a stable level of the medication in the body
• Avoiding the use of LDN in patients taking opioid medications, as it can precipitate withdrawal symptoms
• Using a compounded formulation specifically prepared as low-dose naltrexone, as commercial naltrexone preparations come in much higher doses intended for addiction treatment. The use of LDN has been supported by studies, including a RCT of 31 patients with fibromyalgia, which showed a significant decrease in pain and improved satisfaction with life compared to placebo 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment Treatment of Alcoholism A dose of 50 mg once daily is recommended for most patients Treatment of Opioid Dependence Treatment should be initiated with an initial dose of 25 mg of naltrexone hydrochloride. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter

The standard dosing guidelines for naltrexone are 50 mg once daily for the treatment of alcoholism and 25 mg initially, followed by 50 mg daily for the treatment of opioid dependence. Low-dose naltrexone is not explicitly defined in the provided drug labels, but it can be inferred that doses lower than the standard 50 mg daily may be considered in certain situations, such as when initiating treatment or in patients who are vulnerable to precipitation of withdrawal symptoms. However, the labels do not provide specific guidelines for low-dose naltrexone. 2

From the Research

Low Dose Naltrexone Guidelines

• The daily dose of low-dose naltrexone (LDN) is considered to be between 1 to 5 mg, as stated in the study 3.
• LDN has been shown to reduce glial inflammatory response and modulate Toll-like receptor 4 signaling, in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade 3.
• Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn's disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer 3.
• The use of LDN in the treatment of fibromyalgia has been supported by several studies, including a prospective study that found it to be a well-tolerated and likely effective treatment option 4.
• LDN has also been used off-label for the treatment of pain and inflammation in multiple sclerosis, Crohn's disease, and other diseases, with evidence supporting its safety and tolerability 5.
• A review of the evidence for LDN in chronic pain management found that it resulted in a small decrease in pain, although it may be considered after a patient has failed multiple lines of therapy for additional pain control 6.
• The mechanism of LDN in reducing chronic pain symptoms is thought to be through the modulation of neuro-inflammation, specifically the modulation of glial cells and release of inflammatory chemicals in the central nervous system 7.

Dosage and Administration

• The dosage of LDN can range from 1 to 5 mg per day, with some studies using a dose of 4.5 mg daily 6.
• The duration of LDN therapy can vary, with an average duration of 123 days in one study 6.
• LDN is generally well-tolerated, with common adverse effects including vivid dreams, drowsiness, dizziness, and nausea 6.

Clinical Applications

• LDN has been used in the treatment of various chronic pain conditions, including fibromyalgia, multiple sclerosis, and Crohn's disease 3, 4, 5.
• It has also been used in the treatment of complex-regional pain syndrome and Hailey-Hailey disease 3.
• Further research is needed to fully understand the efficacy and safety of LDN in these conditions, as well as its potential use in other chronic pain disorders 3, 4, 5, 6, 7.