Should You Use Low Dose Naltrexone? Save

There's this low grade buzz from some rheumatologists about the potential analgesic benefits of low dose naltrexone.  I haven't used it. Should you? 

Naltrexone is FDA approved (at much higher doses) to treat alcohol dependence and to block of the effects of exogenously administered opioids.

Low dose naltrexone (LDN) is thought to work by dialing down central sensitization. LDN has been advocated for both chronic and inflammatory pain, with mechanisms that differ completely from standard high-dose naltrexone or traditional opioid pain relievers. LDN briefly and partially blocks opioid receptor and is thought to induce natural production of endorphins and enkephalins to ameliorate pain. Some have postulated that LDN works via TLR4 antagonism, downregulating neuroinflammatory signals.  All speculative. 

But does it work?

I queried OpenEvidence.com about the "efficacy of naltrexone" in arthritis patients.  The response was:

• "Low-dose naltrexone (LDN) has not demonstrated efficacy in arthritis in controlled trials, and the overall evidence is weak. The only randomized controlled trial directly in arthritis — a double-blind, placebo-controlled crossover pilot in osteoarthritis (OA) and inflammatory arthritis (IA) — found no benefit, while supportive data come almost entirely from preclinical models and uncontrolled register-based or observational signals. LDN (typically 4.5 mg/day) is consistently safe, cheap, and well tolerated, but current evidence does not support routine clinical use in arthritis.
• There is no good controlled data.
• Reports of efficacy are limited uncontrolled reports, with vague or subjective outcomes.
• Some promote its primary benefits in fibromyalgia and central sensitization syndromes. 

A recent review of 105 studies and 15 randomized controlled trials  of LDN  showed that in a variety of disorders (chronic pain, autoimmune and neuroimmune disorders, gastrointestinal disease, dermatological conditions, post-infectious syndromes, mental health and oncology), positive findings from uncontrolled studies were not replicated in placebo-controlled trials. High bias was evident with case reports and smaller studies that are prone to publication bias and rely heavily on subjective outcomes. 

The good news is that LDN is safe, inexpensive and well tolerated, with most studies using a daily dose of 4.5 mg.  Common side effects include nausea, vomiting, loss of appetite, joint pain, muscle cramps, headache, dizziness, drowsiness, sleep problems, tooth pain or URI symptoms.

The bottom line is that current evidence does not support routine clinical use of LDN for pain management. LDN may have a pragmatic role in treatment-resistant cases where standard therapies have failed, provided its experimental status and uncertain efficacy are clearly explained. Larger, well-designed RCTs with objective endpoints, along with N-of-1 approaches to identify potential responders, are needed to clarify its true clinical value.