NMSS on LDN

[NHE]

Here's a recent article on LDN from the NMSS' Momentum magazine written by Dr. Allen Bowling...

CAM: Low-dose altrexone (LDN) The “411” on LDN
Low-dose naltrexone, also known as LDN, is an unconventional treatment that is claimed to be effective for treating a number of medical conditions. It has attracted a good deal of attention on the internet, including Web sites run by low-dose naltrexone organizations. Over the last several years, there have been personal stories and hypotheses suggesting that LDN is specifically beneficial for people with MS, but there were no formal studies of LDN in MS — until now. Recently, several research studies have evaluated the safety and effectiveness of LDN in an animal model of MS and in people with MS.

What is LDN?
Naltrexone is an oral drug that is approved by the Food and Drug Administration (FDA) for treating opiate and alcohol addiction. For addiction, the usual dose is about 50 milligrams daily. Much lower doses, ranging from 1.5 to 4.5 milligrams daily, are claimed to prevent attacks, lower disability progression, and relieve symptoms in people with MS. This "low-dose" approach, or LDN, is also claimed to be an effective treatment for other immune-related diseases, including AIDS, cancer, rheumatoid arthritis, and Crohn’s disease.

The LDN studies, to date
In the past year, multiple reports of small or preliminary LDN studies in people with MS and in "EAE,"" the animal model of MS, have become public. Two preliminary EAE studies, reported at the annual meeting of ECTRIMS, or European Congress for Treatment and Research in MS, found that LDN decreased immune cell activation, nervous system inflammation, and disease severity. Preliminary results of a rigorously designed clinical trial in people with MS were also reported at the ECTRIMS meeting by Dr. Bruce Cree at the University of California-San Francisco (UCSF). In this eight-week study, 80 people with relapsing as well as progressive forms of MS were treated with LDN or inactive placebo. LDN treatment had no effect on physical functioning but it did produce improvement in measures of mental health and pain. A smaller Italian study, published in 2008 in the journal Multiple Sclerosis, evaluated the effects of LDN in 40 people with primary-progressive MS over six months. It’s important to note that there was no placebo-treated control group in this study. The primary goal of this study was to assess safety. LDN was generally well tolerated. Only one person had neurological worsening during the study period. In terms of symptoms, LDN treatment was associated with improvement in spasticity, but no effect on depression, fatigue, or overall quality of life, and, surprisingly, a worsening of pain. These contradictory findings illustrate how much more scientists still have to unravel about the actual effects of LDN.

What do we know now?
Overall, these reports seem encouraging, but it must be emphasized that they are not definitive. With the exception of the Italian clinical trial, they have not been published in professional journals. Thus, they have not undergone a rigorous review process. In addition, EAE is an animal model for MS, and positive EAE results must always be interpreted with caution. Finally, the clinical trials have some limitations. As noted, the Italian trial did not include a placebo group, and, thus, some of the beneficial effects could have been due to a "placebo response." The UCSF trial was short term, involved a relatively small number of people, was conducted in only one research center, and was not designed to assess LDN’s effects on disease activity rigorously.

Does LDN have side effects?
The safety of LDN use in MS, especially on a long-term basis, is not yet known. The two clinical trials reported that LDN was generally well tolerated. In the UCSF study, several people reported "vivid dreaming" during the first week of treatment. In the Italian study, some people had mild abnormalities in liver function, blood count and cholesterol. Irritability, which has been noted by some as associated with LDN use, was not a significant issue in either study.

How could LDN work?
There are several theories about how LDN could produce therapeutic effects. One is that LDN, which is an inhibitor of opiate effects, may, paradoxically, increase opiate effects in the body by sparking production of the body’s own opiate chemicals, the endorphins, and by increasing the body’s sensitivity to them. Endorphins may have beneficial effects on symptoms such as pain and mood, and may reduce inflammation. The Italian study found that LDN treatment was associated with increased endorphin levels, which supports this hypothesis. Another theory holds that LDN may decrease the formation of harmful chemicals known as free radicals, protecting nerve cells from injury.

Unanswered questions
While these recent studies increase our interest in LDN, larger and more rigorous studies are needed to get definitive answers to important and still unanswered questions: Does LDN truly decrease the severity of MS symptoms? Does LDN slow down relapsing or progressive MS? Is LDN safe to use in MS over the long term? Does LDN interact with conventional MS medications? Like most of my colleagues, I believe we need answers before LDN can be considered reasonable MS therapy. But because the medication is already FDA-approved for other uses, it can be acquired. Some people with MS may be interested in considering this therapy now. They should be aware of all the limitations of the current scientific information as well as liability and insurance issues (typically insurance will not cover LDN for MS) and discuss the information in detail with a knowledgeable health-care professional.

Dr. Allen Bowling is clinical associate professor of neurology at the University of Colorado-Denver and Health Sciences Center and author of Complementary and Alternative Medicine and Multiple Sclerosis, 2nd edition (Demos Health).

For a list of references to professional articles supporting this column, please see nationalMSsociety.org/LDN or call your Society chapter for a printed copy.

Link to article