Friday, September 29, 2023
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Editor's Note:
Fibromyalgia presents as a chronic musculoskeletal disorder of unknown etiology. Although symptoms associated with fibromyalgia
fluctuate from one person to another, most sufferers complain of "aching all over." The stress associated with the condition
may explain the multitude of other symptoms and features of fibromyalgia, including fatigue, insomnia, morning stiffness,
chronic headaches, restless legs, twitching muscles, facial or jaw pain, mood disturbances, cognitive or memory impairment,
dry mouth, and chest pain/shortness of breath. Although nonpharmacologic approaches can be effective in the short term, a
combined approach involving pharmacologic therapy is recommended for the treatment of the disorder's many presentations. However,
conventional pharmacologic approaches often use unapproved agents that focus on the individual presentations of the disorder
and result in suboptimal patient outcomes.
This interview addresses the current understanding of fibromyalgia and approaches to its management. Helen Fosam, PhD, Medscape Rheumatology, spoke with Rollin M. Gallagher, MD, MPH, Clinical Professor, Psychiatry & Anesthesiology, University of Pennsylvania Center for Pain Education; and Director of Pain Medicine, Philadelphia VA Medical Center, on the perception of fibromyalgia among rheumatologists, including the recent advances in therapeutic agents for its management.
MEDSCAPE: How common is fibromyalgia and how well do clinicians, particularly rheumatologists, recognize it as a true disease entity?
Dr. Gallagher: It is a common enough disease; I think the estimate is that perhaps 20% to 30% of visits to rheumatologists are for widespread pain, like fibromyalgia. I think it's a common complaint that rheumatologist see in their clinics.[1,2]
The diagnosis and the acceptance of fibromyalgia as a specific disease entity has been very controversial for a number of reasons. Most rheumatologists are accustomed to and attuned to making a diagnosis based on blood work and specific findings, such as radiographic and physical findings in the joints. Whereas fibromyalgia has been clearly identified as a central nervous system disease. In terms of its diagnosis, it is much more like other chronic pain syndromes, like a migraine headache where you may not have a specific physical finding except for tender points. There is no pathologic presentation, but there is severe pain, and that's the presentation itself. Nonetheless, there is a pattern to the pain.
The manifestations of the disease have to do with the central nervous system. Symptoms commonly associated with fibromyalgia, such as fatigue, depressed mood, difficulty thinking, as well as various others, are what we might call neuropsychiatric symptoms. This is a clinical area that is generally not within the scope of rheumatology training or expertise.
Among rheumatologists, fibromyalgia has been controversial in regard to whether it is a discrete disease entity because it doesn't fit into what rheumatologists and other medical specialties can identify in terms of specific discrete indicators of a disease that fits into a statistical profile within a range and standard deviations. Having said that, the ACR [American College of Rheumatology] criteria are pretty specific and reliable in terms of identifying fibromyalgia, but then from there it is obviously difficult deciding what the precise pathophysiology is.
MEDSCAPE: You mentioned that some of the symptoms of fibromyalgia are fatigue and depressed mood. What is the psychological impact of fibromyalgia and how does it affect the quality of life of the patient?
Dr. Gallagher: Fibromyalgia has a profound effect on the quality of life of the patient because it does affect cognitive functioning -- in other words, the ability to think, to reason, to remember. It has a widespread cognitive impact.[3,4]
As I mentioned earlier, it has a high association with depressed mood and with comorbid depression. We'll talk about that in a minute, but I think it does have a negative effect on people's lives. It is very disabling, it's very impairing. People can't function at their jobs or in their family lives very effectively.
In terms of quality of life, it has a profound impact like many other chronic-pain diseases and disorders. If you have pain, which impairs function, and you add to that cognitive impairments and emotional liability, you've got a pretty disabling condition.
MEDSCAPE: There has been some debate that fibromyalgia is psychological in origin -- for example, caused by stress or depression -- and should have a psychological approach to its management. What is your opinion on this?
Dr. Gallagher: Recent studies, particularly a large community-sample family study conducted at the University of New Jersey at Newark Medical School by Raphael and colleagues,[5] have shown that fibromyalgia in the community is related to depression in the sense that family members of patients with fibromyalgia have higher rates of depression than normal or control subjects in the community. The rate of depression in these patients is as high as in patients who have major depression.
The family studies have basically demonstrated that there is a common factor predisposing in both fibromyalgia and depression. So they are related, but they are not the same thing. Studies in pain laboratories have shown that, in fact, there is a pain-processing dysfunction in fibromyalgia such that minor signals from the periphery are interpreted as pain in the brain, and the brain areas that express pain definitely light up with minor levels of nociception during imaging studies.
So basically what you have is a central nervous system that is very reactive to even subthreshold painful stimuli. What normal people wouldn't feel as pain is expressed as pain in a patient with fibromyalgia, and the corresponding areas of the brain will light up with pain signals, so it is very real. It's like a central filtering system that's not working right.
MEDSCAPE: So these patients are ultrasensitive to stimuli and perceive them as painful?
Dr. Gallagher: Right; it's very real pain because it activates the pain areas in the brain. It's not like they are imagining it.
I think the psychological factors are important because stress does worsen the pain. There is no evidence currently from the literature that stress and exposure to stress actually cause fibromyalgia, but they do cause the symptoms to worsen, as seen in almost any chronic severe neuropathic or central pain syndrome like this.
Raphael and colleagues previously conducted a study during the 9/11 World Trade Center attacks, an extraordinarily stressful experience in the region, which showed that there was no increase in the development of fibromyalgia among the control patients who didn't have fibromyalgia; in other words, there wasn't an increased rate of fibromyalgia developed, but there was an increase in pain among the fibromyalgia patients.[6]
That was a naturalistic experiment; unfortunately, from a tragedy we were able to learn something about the disease. There are some indicators -- again, from some of the work that Raphael and colleagues[5,6] are doing -- looking at early traumas and whether those, in fact, may lead to fibromyalgia later on.
In fact, there was a study presented here at the ACR meeting showing that some early exposure to situations, such as being hospitalized after an accident in childhood, may lead to a higher rate of widespread pain or fibromyalgia later on. This is a large study being done in Great Britain with many thousands of patients.[2]
There may be some emerging evidence for what we call a vulnerability hypothesis. Some kind of early experiences or early exposures may create a vulnerability to responding later on in life to stress or to other events of minor injuries, with a reduction in the ability to process pain normally. That may be the cause of, or at least one of the causes of, the development of fibromyalgia in certain individuals who are predisposed to the disease.
Furthermore, an individual may have a genetic vulnerability based on whatever the gene is, or whatever the vulnerability is, that makes one either get fibromyalgia or get depression; but then it may be a specific exposure to either trauma or something else early in life that leads later to its manifestation as extreme sensitivity to pain. It's a very complicated issue, but I think some very good scientists are teasing it out now.
MEDSCAPE: What are the diagnostic criteria for fibromyalgia, and how is fibromyalgia differentiated from other presentations of pain?
DR. GALLAGHER: The ACR Criteria are 11 out of 18 tender points that are bilateral, both upper-body and lower-body extremities. Those are the key criteria, but what helps the diagnosis -- and I think this is one of the things that people need to be aware of -- is that regional pain is not fibromyalgia.[7] In other words, you can have myofascial pain syndromes after an accident or trauma of some sort that are localized and regionalized. There can be fairly widespread pain, but it is asymmetric. It starts from the original injury and spreads to other areas that are stressed by splinting or gait changes, etc. That's not fibromyalgia; that's some regional myofascial pain. It's a different diagnosis.
However, even regional myofascial pain like that can also -- like all chronic-pain syndromes -- lead to depression, fatigue, sleep problems, etc, so it can look like fibromyalgia on initial evaluation. Whereas if you evaluate more carefully, you'd find out that it's actually a localized myofascial syndrome with some spread, so to speak. I think that would be a major differential. We see a fair number of patients who are misdiagnosed with fibromyalgia when in fact they have a myofascial pain syndrome that is treatable differently. The treatment for myofascial pain syndrome is a combination of things like trigger-point therapy with vigorous exercise, posture training, etc. It is a very different type of treatment.
The symptoms associated with widespread pain -- tender points bilaterally in upper and lower body and symmetrically -- are also depression, comorbid depression, fatigue, cognitive changes, and sleep disturbance, so those are some of the things that you also look for to solidify the diagnosis.
You can also have pain complaints; they are widespread with depression. But you won't find the physical signs that are so specific to fibromyalgia in patients with depression who are sort of complaining of aches and pains but don't have any specific pain disorder, per se.
MEDSCAPE: In your opinion, how should we approach the treatment of fibromyalgia?
Dr. Gallagher: There is pretty strong evidence that cognitive behavioral therapies help fibromyalgia. Physical therapy helps fibromyalgia and a number of different medications help fibromyalgia. We know a lot more now than we did 10 years ago: Then, we didn't know much about how to treat fibromyalgia; now, we really have some treatments that work, and combining those treatments is the best way to go in terms of managing the disease.
MEDSCAPE: What kinds of medications are commonly used, and is there an evidence base for their use in fibromyalgia?
Dr. Gallagher: The ones that have strong Level A evidence (double-blind, placebo-controlled studies) include pregabalin, fluoxetine, and milnacipran. There is some evidence for the effectiveness of cyclobenzaprine. There is also some evidence that tramadol may be effective, which is interesting because it is a weak agonist, an opioid, with serotonin and norepinephrine agonist properties.
There is some evidence for the effectiveness of the NaSRI [noradrenaline-serotonin reuptake inhibitors] group of antidepressants, now being used in neuropathic pain, but the evidence is not strong. Then the calcium channel blockers like pregabalin and even gabapentin -- apparently there is some evidence now emerging for their effectiveness in fibromyalgia.
There is no evidence at this point that opioids help fibromyalgia. I have not seen evidence for that nor have I had success using it. There are tricyclics that can be effective or there is some evidence for them, but they are not well tolerated.
MEDSCAPE: Were data presented at the ACR meeting on the latest evidence concerning the treatment of fibromyalgia?
Dr. Gallagher: There were a number of posters and papers that were presented. For example, there was a paper from São Paulo, Brazil, investigating the effectiveness of physical exercise and physical therapy on fibromyalgia. This study, led by Dr. Kayo,[8] showed that patients who participated in resistance training and muscular exercise, as well as walking exercises, performed better than the control group who had no exercise at all. Other supportive evidence shows that physical exercise programs, starting very slowly and increasing gradually, can make a difference in patients with fibromyalgia.
MEDSCAPE: This approach appears similar to the approach to treating depression, because exercise is one treatment for depression.
Dr. Gallagher: That is correct; with exercise, you're helping people's mood and outlook. A theoretical explanation is that as soon as you start activating the other sensory systems in the body, not just the nociceptive pain system, it ends up shutting down the pain or tightening up the pain perception system, making it work more effectively. Essentially you are stimulating the brain with more information, and the brain pays attention to that information, such as walking, movement, positioning -- all the things that go along with activity. Being active is very important, but again, so is starting slow and progressing gradually with cognitive behavioral support.
In terms of other data, there were several different papers showing that pregabalin is effective for fibromyalgia,[9-11] and it has recently been approved for that. These results hold up if you follow patients over the long term.
There are also new data showing that milnacipran is effective and safe for the treatment of fibromyalgia.[12-14] This is not yet approved by the US Food and Drugs Administration, but double-blind, placebo-controlled phase 3 studies were presented here by Clauw and colleagues[12] showing that milnacipran is effective for fibromyalgia.
The good news is that we're developing the evidence for a multimodal approach to fibromyalgia that makes things look much more positive for patients but also gives rheumatologist and other providers effective treatments for patients with fibromyalgia.
MEDSCAPE: In your opinion, what are the educational needs -- particularly among rheumatologists -- for improving the recognition, diagnosis, and treatment of fibromyalgia in patients with rheumatoid arthritis?
DR. GALLAGHER: One important concept is helping them develop an understanding of the neuropathophysiology of fibromyalgia and the family studies associating it with depression, but establishing it as different from depression. I think a lot of rheumatologists would tend to lump fibromyalgia with depression, whereas it's not the same thing.
Understanding more about the changes in the brain and central nervous system that occur in fibromyalgia, the concepts of kindling and stimulus augmentation -- those are all important concepts that underlie the treatment approaches that are effective. That's a different territory conceptually for rheumatologists who may be accustomed to looking more specifically at the joints and the pathology of the joints.
Starting off with a theoretical approach to education, and then moving from there to practical instruction on how-to, on the medications that are effective and supported with good data, is important. Furthermore, we should understand that other treatments integrated with the medications can also be effective, so a multimodal approach should be adopted.
I think most physicians like to see the evidence supporting the effectiveness of their approach to treatment. They need to know how to be effective with a syndrome that has been frustrating to treat.
MEDSCAPE: How important is an integrated team for the management of fibromyalgia?
Dr. Gallagher: The key thing here is an integrated rehabilitation program that uses the medications, that uses cognitive behavioral techniques and helps patients adhere to the treatment program and avoid the feeling of helplessness.
Using the medications to help reduce the suffering allows patients to move faster through these programs. Without that, some people can get stuck feeling like they have a chronic disease that will never get better and that they have to give up their lives. I think early identification and aggressive treatment, like for any pain condition, is really the key with this comprehensive approach.
Supported by an independent educational grant from Forest Pharmaceuticals.
