From the Guidelines
Low Dose Naltrexone (LDN) may be effective in reducing fatigue in patients with chronic neuropathic pain, including fibromyalgia, as it has been shown to decrease pain and improve satisfaction with life in a randomized controlled trial (RCT) of 31 patients with fibromyalgia, with a significant decrease in pain and improved satisfaction with life as compared to placebo 1. The typical dosage of LDN for fatigue management ranges from 1.5mg to 4.5mg taken once daily at bedtime, with most patients starting at 1.5mg and gradually increasing by 1.5mg every 1-2 weeks until reaching the target dose. Some key points to consider when using LDN for fatigue management include:
- LDN should be taken consistently for at least 2-3 months to properly evaluate its effectiveness for fatigue
- The medication works by temporarily blocking opioid receptors, which triggers increased endorphin production and modulates immune function by reducing inflammatory cytokines and regulating T-cell activity
- Common side effects include vivid dreams, sleep disturbances, headaches, and gastrointestinal upset, which typically improve after the first few weeks
- LDN requires a prescription and should be obtained from a compounding pharmacy since commercial naltrexone is only available in 50mg tablets
- It's essential to discuss this treatment with your healthcare provider before starting, especially if you take opioid medications, as LDN can block their effects and potentially cause withdrawal symptoms, as it is an opioid antagonist for the μ-opioid and κ-opioid receptors 1.
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 use of different medications for treating fatigue in multiple sclerosis, including amantadine, modafinil, and methylphenidate 4, 5, 6.
- A systematic review and meta-analysis found that amantadine improved MS-related fatigue, with mild side effects and good tolerability 5.
- 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.
Potential for Future Research
- Larger randomized controlled trials are needed to confirm the efficacy of LDN and NAD+ supplementation for treating fatigue in patients with COVID-19 and other conditions 3.
- Further research is also needed to determine the optimal treatment dose and duration for LDN, as well as its potential benefits and risks in different patient populations 2, 3.