Why is it called “Low Dose” Naltrexone?

Low Dose Naltrexone dosages ranging from 0.5 - 6 mg once daily have been used in fibromyalgia patients. These smaller dosages must be made at a compounding pharmacy and the dosage will depend on the individual’s response. Naltrexone is commercially available in Canada as a 50mg tablet to help maintain an opioid-free state in detoxified formerly opioid-dependent people or for the treatment of alcohol dependence.

What is Naltrexone?

Naltrexone works by blocking opioid receptors in the brain. At low doses, researchers think it may work differently, by reducing inflammation in the nervous system and helping reset pain pathways.

Title of Article:  

Efficacy and safety of low-dose naltrexone for the management of fibromyalgia: a systematic review  and meta-analysis of randomized controlled trials with trial sequential analysis 

Date of Publication: 2024

Journal Citation: https://doi.org/10.3344/kjp.24202

Background: 

This article is a systematic review and meta-analysis of double-blind randomized controlled trials (RCTs) looking at the effectiveness and safety of Low Dose Naltrexone (also known as LDN) (1-6mg daily) in the management of fibromyalgia.

1 A systematic review is when scientists look at all the studies that have already been done on a topic to see what the evidence shows.
2  A meta-analysis is when they take the results from all those studies and combine them together to get a bigger, clearer picture of what works.
3  A double-blind randomized controlled trial (RCT) is a type of study where:

• Participants are randomly assigned to either get the real treatment or a fake treatment (placebo).

• Neither the patients nor the researchers know who is getting the real medicine (that’s the “double-blind” part).
  This helps make sure the results are fair and not influenced by people’s expectations.

So simply put, scientists looked at all the best studies where patients were randomly given Low Dose Naltrexone or a placebo, and nobody knew who got what, then combined the results to see if Low Dose Naltrexone really helps fibromyalgia patients.

 

Who was studied: 

Four RCTs with a total of 222 fibromyalgia patients published from 2013, 2023 and 2024.

How was the study conducted: 

An extensive literature search and screening of published papers resulted in the four articles that met criteria.

Findings/Results: 

Effectiveness:

All four studies showed a  significant difference in pain scale scores with LDN compared to placebo (sugar pill).  The change in pressure pain threshold (the amount of pressure someone can tolerate before feeling pain) improved. More patients taking LDN had at least a 30 % pain reduction compared to the placebo. However, improvements in function (like daily activities)were not significantly different. 

Safety:

Most common side effects in the LDN group included nausea and vivid dreams. Less common side effects were headaches, dizziness and diarrhea. Overall side effects were generally mild. 

Limitations of Study: 

The small number of patients makes it difficult to apply to the general fibromyalgia population. Effectiveness of LDN in 30% improvement of pain results may be falsely positive since there were not enough patients studied.  Analysis showed differences in some outcomes which may be because FM is different in everyone or difference in follow-up periods.    

Discussion / Conclusion:

LDN is more effective than a placebo in lowering pain and improving the Pressure Pain Threshold in patients with fibromyalgia. There are multiple suggested ways in which LDN decreases pain. This article gives less biased information than the earlier published case reports. Additional RCTs with more patients and longer follow-up periods are needed to validate our results.

FAC Research Committee Comments:

Low Dose Naltrexone has been used in a limited number of fibromyalgia patients. Some individuals may find it effective in decreasing pain and seems fairly well tolerated. Talk to your prescriber to determine if a trial of Low Dose Naltrexone may be helpful for you.

 

For more Research Lay Summaries go to https://fibrocanada.ca/en/research-highlights