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Fibromyalgia: Few New Treatments, But Understanding Continues to Grow
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Efforts to better understand and treat fibromyalgia are ongoing and multifaceted, with an increased emphasis on both drug and non-drug treatments during the past 20 years. However, because of the complex, highly individualized nature of fibromyalgia causes and symptoms, the condition does not lend itself to a fast-paced drug development pipeline or to the advent of a single treatment that will help all patients.
“I think understanding and treating this condition is best achieved by finding out how the individual patient — one particular patient — got to this disease and identify any potential underlying cause,” Lan Chen, MD, PhD, rheumatologist at the University of Pennsylvania Health System, told Healio Rheumatology. “Maybe this patient has undiagnosed ankylosing spondylitis, or maybe the patient has undiagnosed [rheumatoid arthritis] RA or Sjögren’s syndrome. In some cases, stress is a trigger, if not a cause. I think an effective treatment should be an individualized targeted treatment for each patient.”
A Central Component
Recent research now views fibromyalgia as a “centralized pain state,” according to Daniel Clauw, MD, director of the Chronic Pain and Fatigue Research Center and professor of anesthesiology, medicine and psychiatry at the University of Michigan. This suggests the pain involved in fibromyalgia may originate from, or be worsened by, the central nervous system. This pain may be distinct from pain caused by an injury in that particular part of the body.
“The big thing that a lot of clinicians are missing is that a person may have a strong central component to their pain,” Clauw said. “Most physicians right now are thinking only about the peripheral component of pain. If someone presents with pain in the knee, then there must be something wrong in the knee and if the X-ray doesn’t show it, then the MRI will and if the MRI doesn’t show it, then the arthroscopy will. There has got to be something wrong in the knee to account for the pain in the knee. That’s simply not true.”
Patients with fibromyalgia or other centralized pain states may have diffuse pain and typically experience from fatigue or sleep disturbances. These issues and more were addressed in the 2011 Fibromyalgia Survey, which was developed as an alternative to 1990 criteria issued by the American College of Rheumatology. These earlier criteria, which were intended to be research classification criteria, limit the classification of fibromyalgia to patients with widespread pain, as well as tenderness in 11 or more of the 18 possible “tender points.” With such stringent parameters, these criteria may exclude a significant number of patients with fibromyalgia.
The 2011 criteria include a patient self-report survey that asks not only about the locations of pain, but also about the presence and degree of fatigue, sleep disturbances, memory difficulties, headaches, irritable bowel and mood disorders.
Clauw said when he sees a patient who presents with pain, he asks questions similar to those posed in the 2011 Fibromyalgia Survey.
“I do a history. I ask people how many different areas of the body hurt now and how many different regions of the body they have hurt during the course of their lifetime,” he said. “I ask if they have had some of these other symptoms, like fatigue, sleep problems, memory problems and mood issues now or over the course of their lifetime. What that does is interrogate whether there is a potential central nervous system component to the pain.”
In some cases, fibromyalgia is secondary to an underlying condition. Chen said she considers this possibility when assessing a patient with fibromyalgia.
“I take on fibromyalgia patients if they have a rheumatological condition. When I see a patient with Sjögren’s syndrome, rheumatoid or even polyneuralgia rheumatica and I feel I can contribute to treating them, I will,” Chen said. “If the patient’s fibromyalgia is related to depression or an endocrine issue, then I can’t really help them. I refer them to a physician who can.”
Role of Exercise
One of the main non-drug treatments that has been effective in decreasing fibromyalgia symptoms is low-impact exercise.
“Exercise is important,” Chen said. “I recommend an average of 1 hour per day, 6 days a week. You can start with half an hour and advance slowly, but you cannot just sit there and not do anything.”
However, the recommendation to exercise is often intimidating to patients with fibromyalgia, Clauw said. He said he tries to minimize perceived exercise barriers by not using the term “exercise.”
“I focus on using the term ‘active’ rather than ‘exercise’ because patients will say ‘Well, I can’t possibly do exercise,’’ he said. “I suggest that they become more active. Anyone can do a gentle walking program, even if it means the first time you start walking you can only walk 5 [minutes] or 6 minutes. Then, your goal will be to do 7 minutes the next week and 8 [minutes] the following week.”
Clauw said although patients with fibromyalgia commonly report exercise intolerance, the adoption of a realistic, attainable exercise program ultimately helps with fibromyalgia pain.
“There’s no excuse for not becoming somewhat more active because the pain in fibromyalgia gets worse with inactivity,” he said. “Fibromyalgia pain may worsen if the patient sits for prolonged periods of time. It’s not like osteoarthritis of the knee, where the more you use the knee, the more it hurts.”
Improve Sleep Hygiene
Chen said another important step in fibromyalgia management is to ensure patients with fibromyalgia get an adequate amount and quality of sleep.
“You may need a sleep study to figure out if the patient has sleep disorders,” she said. “Sometimes, the patient may be depressed and this is causing the sleep disturbance. You can try to address these issues together with your patients.”
Clauw said sleep disturbances may originate in the central nervous system and may affect some of the same brain neurotransmitters that also cause depression.
“Most people know that the neurotransmitter serotonin is low in people with depression and some antidepressant drugs raise serotonin or norepinephrine,” he said. “What people don’t understand is that just as low serotonin in certain brain regions causes depression, low serotonin in other brain regions causes you to not sleep well or to have pain.”
He said this concept is validated by the efficacy achieved by drugs like duloxetine (Cymbalta, Eli Lilly) or pregabalin (Lyrica, Pfizer).
“One of the reasons we know these neurotransmitters are part of the key is that when someone takes a drug like Cymbalta or Lyrica, only about a third of the people will get better. But if they do get better, they usually don’t only get better in pain,” he said. “When a patient responds, they’ll usually get better sleep and a deeper sleep.”
Use of Medications
Drugs currently being used to treat fibromyalgia, while beneficial to many patients, were originally developed for other indications, Clauw said. He emphasized, however, that certain drugs intended for more localized types of pain generally do not work for fibromyalgia.
“We need to teach both patients and clinicians that for this kind of pain, the classic drugs like nonsteroidal anti-inflammatory drugs, and especially opioids, have not been shown to be effective for fibromyalgia,” he said. “So right from the get-go, we’re looking to use the drugs that are working more so in the brain.”
Clauw said tricyclic drugs and serotonin epinephrine reuptake inhibitors were originally developed for depression, while gabapentenoid drugs, such as pregabalin and gabapentin, were originally developed for seizures.
“Because the neurotransmitters in the brain that these drugs work on are ubiquitous and do a lot of different things, drugs that work for one indication may have a broader set of conditions that the drug also happens to help,” he said.
There are no current drugs that work only on a single brain region, Clauw said, so when the drug is given to a patient, it goes to the whole brain.
“We don’t yet have the ability to target a drug to go just to one region of the brain,” he said. “But if you match the right drug with the right neurotransmitter that is too high or too low in that patient, their fibromyalgia symptoms get better.”
Cognitive Behavioral Therapy
Clauw said many different studies have supported the use of one-on-one cognitive behavioral therapy for patients with fibromyalgia. This type of therapy can help patients with the psychological components of fibromyalgia, such as catastrophizing pain or fear of movement due to the prospect of worsening pain. These aspects of fibromyalgia are known to be poor prognostic factors, and mitigating these through therapy may help significantly.
“It is therapist-dependent, though – some therapists are great, and they figure out ways to be empathetic with their patients and help them work through issues. Some of them are not as good. They’re like any other group of providers, so the patient has to ask around.”
Other obstacles to one-on-one therapy include limited access to providers and often, a lack of reimbursement by third-party payers. For patients who may be impeded by these factors, an online resource developed by the University of Michigan may help, Clauw said.
“It’s free and we keep making enhancements to it,” he said. “We tested it in a trial and it worked well in people with fibromyalgia. If someone doesn’t have access to a local therapist who will provide cognitive behavioral therapy, they can get a lot of the same things by going to the website.”
Avoid Judgment
Regardless of the treatment strategy used, clinicians should always remember to show empathy to patients with fibromyalgia, many of whom are anxious about or troubled by their condition.
“You have to open your ears and listen to them,” Chen said. “Nothing is objective in patients with fibromyalgia. They’ll sometimes test normal, but it’s important to validate that there is a condition called fibromyalgia and it hurts everywhere. Sometimes just being compassionate is an important part of the treatment for these patients.”
Chen noted that because there is no predictably effective treatment for fibromyalgia, some clinicians may avoid these patients.
“Many physicians, when they recognize a fibromyalgia patient, will close their doors to them and some may just close their understanding to them,” she said. “That’s a negative response. You have to avoid being judgmental in your understanding of these patients.”
Clauw said he tries to manage patient frustration by establishing realistic goals from the outset.
“With fibromyalgia, patients can’t just sit around on their couch and wait for scientists to find a cure,” he said. “I understand why these patients get disappointed and discouraged, but they need to try these interventions that we have, because that is the nature of successful pain care. I always tell my patients that they should expect to hit a lot of singles, not a lot of homeruns.” – by Jennifer Byrne
- References:
- https://fibroguide.med.umich.edu/fibroguide.html
- Wolfe F, et al. J Rheumatol. 2011;doi:10.3899/jrheum.100594.
- For more information:
- Lan Chen, MD, can be reached at 3910 Market St., Philadelphia, PA 19104; email: greg.richter@uphs.upenn.edu.
- Daniel Clauw, MD, can be reached at 24 Frank Lloyd Wright Dr., Ann Arbor, MI 48105. email: dclauw@med.umich.edu or karbro@med.umich.edu.
Disclosures: Chen reports no relevant disclosures. Clauw reports he is a consultant, advisory, strategic, scientific or medical board member for Abbott Pharmaceutical Products Division and Pfizer; is on an advisory, strategic scientific or medical board for Zynerba, Astellas Pharmaceuticals and Cerephex; is an expert witness for Williams & Connelly LLC; lecturer for Pierre Fabre; and consultant for Aptinyx, Daiichi Sankyo, Samumed, Theravance and Tonix; and receives research support from Aptinix, Cerephex and Pfizer.