I am in the process of researching a potential new treatment for my Lyme disease, and this post is a place for me to summarize what I am finding. As I describe elswhere in my blog<link>, I think it is important to consider any treatment plan from multiple perspectives. In this case my research includes the mechanism by which it functions (“process data”), clinical trials (“frequency data”), the impact of side effects (potential risks), and patient experiences
(Lyme patients and also other diseases). I’ll go through each in order. The treatment I’m exploring is Low Dose Naltrexone (note I am linking to the Wikipedia article, which as of this writing is at best incomplete, since it does not include all the trials that have been done). A potentially better source is lowdosenaltrexone.org, which is run by the doctor who discovered this use of the drug and two other doctors.
These facts are primarily taken from the website run by the doctor who discovered its impact on the immune system, Dr. Bihari. To summarize a description of how LDN functions: Naltrexone is an opiate binder and it originally was designed to help heroin addicts (however this was unsuccessful due to the side effects at the 50mg dose used in that context). The side effects are due to it blocking endorphins (which heroin resembles). Endorphins are hormones that are associated with pleasure, but also affect the immune system. Naltrexone helps to increase endorphin production, paradoxically, by blocking it for a brief period. This appears to cause the body to produce increased endorphins in reaction.
This is not the only hypothesis about how things work — for example I found a 2005 article in the journal Medical Hypothesis that was a bit hard to follow but seemed to argue that LDN reduced the formation of a compound that inhibits transportation of a neurotoxin, in MS patients (Agrawal, 2005). On the other hand, a 2008 publication in the same journal conforms more to the Bihari view of the world (Brown & Panksepp, 2008).
Dosage & other issues should (ideally) be discussed with your doctor. I did find the following warnings: LDN cannot be taken along with narcotics, and given its function is not ideal to take with immune-suppressants. It is typically supplied (with a prescription) by a compounding pharmacy. This site advises not taking a “slow release” or “long acting” form and the same site advises not compounding it with calcium carbonate as a filler.
Clinical trials & other research:
Published studies seem to go back to around 2005, but the drug has been around since about 1984 (Brown & Panskepp, 2008). There are a couple of recent results that are worth talking about. Smith et al. (2013) published a pilot trial with fourteen children with Crohn’s disease showing significant positive outcomes and no serious adverse events.
In other news, the innovative site CureTogether started a trial in 2010. CureTogether takes large scale patient data and pulls out analyses that would otherwise not be possible — not clinically controlled trials but they have discovered new disease mechanisms in the past, for example. Their study replicated the positive findings of a smaller study that was more traditional, both showing benefits for patients with Fibromalgia. That traditional study, Younger & Mackey (2009) was small (10 participants) but very well run (double blind, placebo controlled, within subject). Everyone in the study improved, with some improvements of greater than 30% over the placebo. One possible flaw in the study is that all patients received the placebo first (something they might have guessed at), however the placebo and drug periods were different lengths which might help to mitigate this. The biggest impacts were on pain, fatigue and stress (but not headaches, concentration, and sadness). Patients with the highest baseline sed rate (ESR) were most responsive (.91 correlation) (something the authors say is also true of an earlier Crohn’s trial from 2007 that I haven’t read).
Finally, a follow up study was done with thirty-one fibromalgia patients similar to the first but with a longitudinal design (Younger et al., 2013). This trial was counterbalanced (removing one concern from the prior one) and showed similarly large improvements. The big impacts were on pain and quality of life, with less impact on fatigue or sleep. Also only 32% of participants responded in a large way.
For patient experiences I searched primarily for Lyme patients. However I also looked at other diseases. In particular I found a compilation of anecdotes by MS patients (from 2009) that was very interesting, some reports as much as 4 years out from the start of treatment. Given that MS is believed to be misdiagnosed Lyme in some cases, and overlaps Lyme in the symptoms even if not the cause, and that doctors are not all supportive of using LDN for MS, I think this is very interesting.
Lyme patients report known side effects (such as sleep). Some discussion of herxing on it is also found (I have never “herxed” and my LLMD was skeptical of the concept, it is not something I have researched. So I use the terminology of the patient community but retain some skepticism as to what it says about LDN). Some very positive statements about it (e.g. read the last post at the bottom of this page).
The risks at low doses seem fairly low. There may be some interaction with other medications (I mention a few above: opiods & immunes suppressors). Thyroid patients should also read up, and there may be some impact on the liver in very large doses. I found comments about it affecting sleep, and causing vivid dreams. I am sure this list is not complete, and anyone taking the drug should research this. Keep in mind that low dose naltrexone should have less significant side effects than the approved (high-dose) version, but similar side effects may be possible.
I’m going to try it. The risks are low, and the rest is promising. Some things that might be worth doing before trying it: measuring my sed rate and the endorphin levels in my body, and tracking the impact. Not sure if I will bother — I have reached a point where I care more about whether I feel good and less about the details, or maybe I’m just tired of writing everything down :). An open question for me is how my immune system can on the one hand be highly functional (all winter I’ve had occasional sore throats when the kids got sick but never developed a cold) and on the other hand need a boost. I guess we’ll see what happens :).
* means I have read the abstract only
*Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. (2013) Safety and Tolerability of Low-dose Naltrexone Therapy in Children With Moderate to Severe Crohn’s Disease: A Pilot Study. J Clin Gastroenterol. 2013 Apr;47(4):339-45. doi: 10.1097/MCG.0b013e3182702f2b.
Younger, J., Mackey, S. (2009) Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study. Pain Med. 2009 May–Jun; 10(4): 663–672. Published online 2009 April 22. doi: 10.1111/j.1526-4637.2009.00613.x
Agrawal, Y. P. (2005). Low dose naltrexone therapy in multiple sclerosis. Medical Hypothesis, 6-4, 721-724
Brown, N. & Panksepp, J. (2008). Low-dose naltrexone for disease prevention and quality of life. Medical Hypothesis (2008), doi:10.1016/j.mehy.2008.06.048
*Younger, J., Noor, N., McCue, R., Mackey, S. (2013)
Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734.