Results of a new study reported at the recent American Academy of Pain Medicine 28th Annual Meeting show that treatment with low-dose naltrexone (LDN) significantly reduces daily pain in those who suffer from fibromyalgia.
Naltrexone is an opioid antagonist drug whose main use is in the treatment of drug addiction. However, when used at much lower dosages in the region of 1.5 to 4.5mg it has been found to modulate immune function and have beneficial effects on the brain. This has led to its use "off-label" for the treatment of a variety of autoimmune and other chronic diseases, from multiple sclerosis and Crohn's disease, to chronic fatigue syndrome and fibromyalgia.
The discovery of the beneficial effects of LDN are attributed to Bernard Bihari, MD, a physician with a clinical practice in New York City, who in 1985 discovered its effects on the body's immune system helped aided HIV-positive patients. He soon found LDN was also beneficial for his patients with various forms of cancer and also those with autoimmune diseases such as lupus. Since then many other physicians have begun prescribing LDN for their patients but large scale, quality clinical trials and the official backing of the medical establishment have been lacking.
Now, researchers from Stanford University School of Medicine in Palo Alto, California, led by Dr. Jarred Younger, PhD, have conducted a double-blind, placebo-controlled trial of LDN in women with fibromyalgia.
The study involved 27 women with fibromyalgia with an average age of 43 who were not taking any opioid pain medications and had no history of rheumatologic disorders. The trial was of a crossover design so patients were asked to record daily pain and symptoms on a handheld computer during several distinct phases; 2 weeks of baseline monitoring, 12 weeks of low-dose naltrexone at 4.5 mg/day, 4 weeks of placebo, and 4 weeks of follow-up.
Dr. Younger stated that daily recording of symptoms was a strength of the study because "It allows us to explore some really complex temporal dynamics of what happens when patients start taking [active] drug, how long it takes before they start feeling better, [and] what happens when they switch [to no active treatment]."
He added that in fibromyalgia this is particularly important because symptoms can vary so much from day to day anyway.
The scientists revealed that LDN treatment produced a 48.5% reduction in pain compared to baseline versus a 27.4% reduction when patients were taking the placebo. These results had a high degree of statistical significance (P=0.006), i.e. reliability.
The fibromyalgia patients also rated LDN to be just as tolerable as placebo overall, with only vivid dreams and headaches being reported more often.
Dr. Younger said he believes that, at such a low dose, naltrexone is not having an opioid antagonistic effect, but is actually acting to suppress the function of microglia, which have been hypersensitized by some unknown trigger — whether an immune response, a physical trauma, or genetic predisposition. Microglia are stationary immune cells found in the brain that are the equivalent of macrophages found elsewhere in the body. Their job is to engulf pathogens and other foreign material and break it down.
"Something is sensitizing these microglia, and when they become activated, they release these proinflammatory cytokines and other agents.... When cytokines are released into the central nervous system, we know they cause sickness behaviors, and I think sickness behaviors induced by cytokines look a lot like the symptoms of fibromyalgia," he said.
Dr. Younger's use of the term "sickness behaviors" does not mean he is implying fibromyalgia is psychological. Sickness behaviors are a natural response to infection or injury initiated by the immune system. For example, if we have the flu we feel sleepy, not due to the virus itself but due to chemicals released by the immune system to encourage us to rest and allow energy to be used to fight off the infection.
The microglia theory is novel as other researchers and physicians have often put forward an alternative explanation for LDNs apparent beneficial effects as Dr. Younger explains: "Others suggest that by temporarily blocking opioid receptors, you cause a subsequent increase in opioid levels later, but I don't think this is what is happening."
Whatever the mechanism the results of the this study provide compelling evidence that LDN is an effective treatment for fibromyalgia and is very safe compared to many alternatives drugs commonly prescribed. The only downside is that naltrexone is not currently available in the low doses required so must be formulated by a compounding pharmacy rather than being available at the local drugstore.
Source:American Academy of Pain Medicine (AAPM) 28th Annual Meeting: Abstract 251. Presented February 24, 2012