From the Guidelines
Low Dose Naltrexone (LDN) may be effective in reducing fatigue in patients with chronic conditions, particularly fibromyalgia, as evidenced by a significant decrease in pain and improved satisfaction with life in a RCT of 31 patients with fibromyalgia treated with LDN 4.5 mg 1. The typical dosage of LDN for fatigue management ranges from 1.5mg to 4.5mg taken once daily at bedtime, with a recommended starting dose of 1.5mg and gradual bi-weekly increase of 1.5mg to a final maximum dose of 4.5mg, as suggested by the study on neuropathic corneal pain management 1. Some key points to consider when using LDN for fatigue management include:
- The mechanism behind LDN's effectiveness involves temporarily blocking opioid receptors, leading to increased endorphin production and reduced inflammation through glial cell modulation, which may help reduce fatigue by decreasing systemic inflammation that contributes to fatigue symptoms.
- Common side effects of LDN include headache, tachycardia, and vivid dreams, as reported in the study on neuropathic corneal pain management 1.
- LDN should be obtained as a compounded medication from a pharmacy that specializes in compounding, as commercial naltrexone tablets (50mg) are too high in dosage.
- Patients should expect that it may take 2-3 months to experience the full benefits of LDN treatment.
- LDN is generally well-tolerated but should not be used by patients taking opioid medications, as it can precipitate withdrawal symptoms.
From the FDA Drug Label
Alcoholism In an open label safety study with approximately 570 individuals with alcoholism receiving naltrexone hydrochloride, the following new-onset adverse reactions occurred in 2% or more of the patients: ... fatigue (4%) Postmarketing ExperienceData collected from postmarketing use of naltrexone hydrochloride show that most events usually occur early in the course of drug therapy and are transient... Events that have been reported include ... fatigue The FDA drug label reports that fatigue is a possible adverse reaction associated with naltrexone hydrochloride, occurring in 4% of patients in an open-label safety study and also reported in postmarketing experience.
From the Research
Low Dose Naltrexone (LDN) and Fatigue
- LDN has been used as an off-label treatment for several chronic immune-modulated disorders, including chronic fatigue syndrome, with some studies suggesting efficacy in reducing fatigue symptoms 2.
- A case series of three patients with chronic fatigue syndrome reported a range of responses to LDN treatment, from life-changing to a reduction in some symptoms only, with treatment doses ranging from 4 to 12 mg 2.
- A pilot study of 36 patients with persistent moderate/severe fatigue after COVID-19 found that treatment with LDN (4.5 mg/day) and NAD+ supplementation improved fatigue symptoms and quality of life, with 52% of patients responding to treatment after 12 weeks 3.
- The study also found that treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments 3.
Comparison with Other Treatments
- Other studies have investigated the efficacy of different treatments for fatigue in multiple sclerosis, including amantadine, modafinil, and acetyl-L-carnitine 4, 5, 6.
- A systematic review and meta-analysis found that amantadine improved MS-related fatigue, with mild side effects and good tolerability 4.
- A pilot randomized, blind study found that amantadine improved fatigue in patients with relapsing-remitting MS, while modafinil and acetyl-L-carnitine showed no or only a trend of improvement 6.
- A randomized, placebo-controlled, crossover clinical trial is ongoing to compare the efficacy of amantadine, modafinil, and methylphenidate in patients with MS-related fatigue 5.