What is the scientific base for use of low dose naltrexone in autoimmune diseases

Fråga: What is the scientific base for use of low dose naltrexone in autoimmune diseases such as multiple sclerosis and autoimmune arthritis? In Norway low dose naltrexone exists as LDN (3mg).

Sammanfattning: LDN has been given as experimental treatment against various diseases, especially autoimmune diseases and pain conditions for the past 20 years. However, we cannot find any well-designed studies that can currently support that LDN could be effective against these diseases.

Svar: Naltrexone is a specific opioid antagonist registered in Sweden for the treatment of alcohol abuse, as co-treatment with psychological support (1). The mechanism of action of naltrexone for treatment of alcoholism is not completely understood but it is believed that the influence on the endogenous opioid system plays an important role. Treatment with naltrexone in patients with alcohol abuse reduces the risk that a small dose of alcohol will trigger uncontrolled alcohol consumption (1).

Since more than 20 years attempts have been made to treat patients with a variety of diagnoses with low dose naltrexone (also called LDN), ie with doses of 3-5 mg (normal dose in the treatment of alcohol abuse is 50 mg). The diagnoses include Crohn´s disease, fibromyalgia, multiple sclerosis (MS), ulcerative colitis, SLE, HIV/Aids, and others. Information regarding LDN is mainly available through various websites run by patients who have themselves had positive experiences of such treatment (2).

A search of PubMed generates many hits on LDN. Most clinical studies of LDN are pilot studies of low quality, many without control groups or randomization. The numbers of patients in the studies are also low, making it difficult to draw conclusions. In most cases, however, patients seem to tolerate LDN well, which is perhaps not surprising given the low dose.

In LDN treatment (<5 mg/day) it is believed that the effect of naltrexone changes from blocking opiate receptors to an agonist role triggering prolonged release of endogenous opioids, such as beta-endorphins (3). Low levels of beta-endorphins have been reported for many diseases, including rheumatoid arthritis, Crohn´s disease and fibromyalgia (4). There is even a theory that naltrexone reduces apoptosis of oligodendrocytes, which could work in the treatment of MS (3). In an open-label, uncontrolled study of 40 MS patients LDN was well tolerated, spasticity was decreased, but there was increased pain and no difference in depression, fatigue or quality of life during the 6 months follow-up (5). However, a double-blind, placebo-controlled, randomized study of 96 MS patients could not detect any difference in mental and physical health between patients taking LDN and those who received placebo (6). According to a leading MS specialist at the neurology department at Karolinska University Hospital, only a few MS patients have tried LDN in Sweden and the Swedish MS Society does not believe that there is enough evidence to support the treatment.

There is a Cochrane review of the treatment with the LDN in Crohn´s disease (7). This is based on two studies with a total of 46 patients, comparing LDN with placebo. The Cochrane review states that one cannot draw any conclusions regarding efficacy or safety of the studies because they are too small. However, one study suggests some endoscopic and clinical improvement in the LDN group, and none of the studies showed a higher incidence of adverse events compared with placebo (7). There are even a few studies of LDN effects in patients with fibromyalgia (8), but these are small and of low methodological quality which makes it difficult to draw any conclusions from their results. In all the above mentioned studies, patients received treatment with naltrexone at a dose of 4.5 mg/day.