A New Day Dawns for the Treatment of Fibromyalgia

I. Jon Russell, MD, PhD

Dr. Russell is Associate Professor of Medicine, Director of the University Clinical Research Center, The University of Texas Health Science Center

Dr. I. Jon Russell is a rheumatologist who has extensive clinical research experience with pain. He is well versed in the painful rheumatic diseases, the myofascial pain syndrome, the complex regional pain syndromes, and diabetic neuropathy, but his true focus is on the pathogenesis and treatment of the fibromyalgia syndrome (fibromyalgia, FMS). For the first time, thanks in large part to the hard work of Dr. Russell and his colleagues, clinicians actually have some promising treatments to offer those suffering from FMS.

Epidemiology

The availability of viable treatment is welcome news for both doctors and their patients. Fibromyalgia affects upward of 2% of the population, both in America and worldwide. Due to the lack of visible symptoms, this disorder was not taken seriously for many years. At least 7 out of 10 people with fibromyalgia are women, and its prevalence increases with age in both sexes. There is evidence to support a genetic basis for this condition. Dr. Russell and his colleagues recently identified two candidate genes that are highly associated with symptomatic individuals in families that have more than one affected individual. One of the involved genes relates to a serotonin receptor but the second is believed to influence immune function in some way. One of these genes predicts early, mild onset of the syndrome, while the other predicts later, more severe onset plus associated irritable bowel syndrome. The universal symptom in this condition is pain, but almost 80% also have persistent insomnia and about 40% exhibit signs of depression.

Diagnosis

Fibromyalgia is a clinical disorder characterized by unusual pain and tenderness called allodynia. As Dr. Russell explains, “allodynia refers to pain that is perceived in response to stimuli that would not normally elicit pain—a gentle hug for instance.”

He cautions that many clinicians incorrectly label fibromyalgic pain as hyperalgesia—however, hyperalgesia refers specifically to over-aggressive pain responses to stimuli that do normally elicit some pain. Patients often feel as if their skin is burning or shrinking, but, unlike in scleroderma, the appearance of the skin remains unchanged. Fibromyalgia is also distinguished from regional myofascial pain syndrome in that, although the pain of FMS may seem to begin in one body location, it quickly (over a few months) becomes generalized to involve the entire body. In addition, the tender points of FMS do not refer pain as do the trigger points of the myofascial pain syndrome. Many FMS patients also demonstrate mild cognitive deficits—they tend to be worried about being forgetful, and will make lists to help them remember. Dr. Russell suspects that the cognitive problems result directly from the patients’ long-term sleep deprivation. Patients with fibromyalgia are often stiff in the morning, and are sometimes misdiagnosed with rheumatoid arthritis. Depression occurs in 40%–50% of people with fibromyalgia, and anxiety is present at about the same rate. Dr. Russell believes that chronic insomnia may be responsible for these comorbidities as well. Many patients (~40%) also suffer from irritable bowel syndrome.

Some clinicians incorrectly suspect people with fibromyalgia of malingering but objective evidence strongly supports its basis as a central nervous system neuropathic condition. A recent panel, on which Dr. Russell was a participant, found published evidence for many interrelated biological measures. “People with FMS have measurable abnormalities in neural chemicals, and fMRI studies have demonstrated distinct abnormalities in pain perception consistent with central allodynia,” Dr. Russell says.

Treatment

Past studies have shown the value of tricyclic antidepressants in treating the pain of patients with FMS but there has always been concern about the high incidence of adverse events with them.

“Many years ago, I published a successful study in which people with FMS were treated with a combination of alprazolam and ibuprofen,” Dr. Russell says. “But the real breakthrough was with tramadol. It was the first drug to give us a 10 -3 p value for the treatment of fibromyalgia.” Duloxetine and pregabalin, both of which are approved for diabetic neuropathy, have shown substantial benefit for people with FMS. Duloxetine relieves both pain and depression, while pregabalin reduces pain and restores regular sleep patterns. Dr. Russell believes that there is reason to think that these two drugs might work well if prescribed together.

Another drug that has shown substantial promise is sodium oxidate. Dr. Russell recently reported to the American College of Rheumatology in San Diego regarding a successful study of that drug for treating FMS. “Sodium oxidate is a sedative, and was expected to restore regular sleep patterns,” Dr. Russell says. “In addition, it also reduced the severity of the body pain. We don’t think sodium oxidate acts directly on nociception, so it seems likely that the benefits in pain reduction were the product of enhanced restorative sleep.” Other studies have shown that if you deprive healthy normal people of stage 3 and 4 non-REM sleep they begin to experience aches and pains with the pattern of allodynia. The mechanism responsible for this interaction is not yet clear, but Dr. Russell believes it’s a promising avenue for further research.

Patients with fibromyalgia also benefit from exercise and education. One interactive educational program that has pretty consistently met with success is cognitive behavioral therapy. “Often,” according to Dr. Russell, “just knowing that their pain is caused by fibromyalgia, and isn’t the result of some frightening and shadowy unknown condition, can be very helpful in regard to patient outlook.”

Conclusion

“The fibromyalgia syndrome is a very common clinical disorder,” Dr. Russell says. “It’s a world-wide problem, and there are 5 million people with fibromyalgia in the US alone. This is an exciting time for fibromyalgia patients, as increasing amounts of energy, expertise, and funding are being poured into fibromyalgia-related research.” Scientists are now finding promising results. There are 5 promising drugs available on the market with published experience in FMS, and more treatments are sure to follow.

“Psychiatrists can make a difference with this condition,” Dr. Russell believes. “By virtue of their insight into the human experience and the mechanisms of action of psychotropic drugs, they have a great deal to offer.”

Disclosure: Dr. Russell is a consultant to Cypress, Eli Lilly, Forest, Janssen, and Pfizer; is on the speaker’s bureaus of Merck and Pfizer; and receives grant support from Pfizer.

Sources: http://www.niams.nih.gov/hi/topics/fibromyalgia/fibrofs.htm#fib_i and http://www.fmaware.org/fminfo/brochure.htm