Daniel J. Clauw, MD, Philip J. Mease, MD, Bret S. Stetka, MD
Editor’s Note: In response to a number of recent advances in the understanding, diagnosis, and management of fibromyalgia (FM), Medscape recently spoke with Daniel J. Clauw, MD, Professor of Anesthesiology, Medicine (Rheumatology), and Psychiatry at the University of Michigan; and Philip J. Mease, MD, Clinical Professor in the Departments of Rheumatology and Internal Medicine at the University of Washington School of Medicine, about the latest evidence and care standards in this puzzling, painful condition.
What Is Fibromyalgia?
Medscape: Can you briefly summarize how the understanding of FM has evolved over the years?
Dr Clauw: In the old days (prior to 1980 or so), FM was called fibrositis—implying that there was some type of inflammation in the connective tissues causing widespread pain. The name was changed to “fibromyalgia” when it became clear that there was no such inflammation. That led to lots of research looking at the role that the central nervous system (CNS) plays in contributing to the pain, fatigue, sleep, and memory problems that these individuals experience. That research—and a parallel movement to study the CNS in other chronic pain states—has led FM to the present point, where it is thought to be the poster child for a “centralized” pain state. This can occur in isolation or as a comorbidity with other primarily “peripheral” pain states (eg, osteoarthritis, rheumatoid arthritis, lupus).
Dr Mease: I agree with Dan’s synopsis of where we currently are in our understanding about FM as a condition characterized by “central sensitization,” or a state in which one can see an increase in “bad” neurochemicals in the CNS that are associated with the experience of pain, fatigue, sleep disturbances, and the so-called “fibrofog”; along with a decrease in compensatory neurochemicals that normally work to offset the effects of these “bad” neurochemicals.
Some of this is triggered by chronic pain stimuli, such as conditions like osteoarthritis or irritable bowel syndrome; but it is also probably influenced by genetic factors, such as the genes that control the synthesis of catechol-O-methyltransferase. Constitutional influences such as early life stressors, which may influence genetic or epigenetic elements in a person, may also contribute to the condition.
If we go back in history to the late 1800s, we find descriptions of “neurasthenia” and other terminology that suggested that patients with chronic musculoskeletal pain without obvious tissue pathology had a primarily psychiatric/psychosomatic/neurotic reason for their symptoms. Because FM occurs primarily in women, they were considered to be weak, sensitive, depressed, anxious, and in need of psychotherapy.
However, in the early 1900s, pathologists incorrectly thought that they saw evidence of inflammation in muscle tissue of FM patients, as Dan has pointed out. There was even a fad for a while in the early part of the last century of removing organs such as the appendix or others that were thought to be the source of some kind of infectious stimulus to inflammation in tissues! Fortunately, these ideas were ultimately laid to rest. Whereas it is true that we may see a slightly higher frequency of depression or anxiety in FM than in the general population, we now know that there is a more biologic basis for the condition than being a pure psychiatric disease.
In the 1970s, Harvey Moldofsky did pioneering sleep studies that demonstrated that many FM patients have a fundamental abnormality in sleep physiology. But here too we now realize that this is an important associated problem but not necessarily the primary root of the condition. So now in the 21st century, with the aid of sophisticated neuroimaging techniques; neurochemical studies of the CNS; genetic analyses; as well as family, developmental, and psychological studies, we are recognizing that FM results from a complex interplay of neurochemical and genetic dysregulation, perhaps in the context of psychological factors; it can occur either on its own or in association with many chronic diseases, especially chronic pain and inflammatory diseases.
Evolving Diagnosis
Medscape: The thinking around diagnosing FM has changed recently, with the latest criteria no longer requiring the tender point counts they once did. How do the two of you now approach diagnosing the disorder?
Dr Clauw: Clinicians can use either the 1990[1] or 2010[2]diagnostic criteria, but these criteria were really meant to be used for research studies, not to diagnose individual patients in practice. This is true of most criteria. We generally recommend that physicians learn to recognize the pattern of widespread pain accompanied by fatigue, sleep, memory, and mood problems and then use the FM label when that is the most likely explanation of those symptoms. Clinicians are very comfortable diagnosing conditions such as osteoarthritis, chronic low back pain, and headache without knowing the formal research criteria for those diagnoses.
Dr Mease: I would like to expand on what Dan has alluded to. It is appropriate to remind ourselves about the difference between classification criteria, which the 1990 FM criteria are, and diagnostic criteria, which the 2010 preliminary American College of Rheumatology (ACR) criteria are intended to be (“preliminary” means proposed but not yet formally accepted before further evaluation occurs). Classification criteria are intended to identify subjects with enough similar features that they can be considered reliably classified for the purposes of research on their condition. Here specificity is more important than sensitivity (ie, more definitively includes correctly diagnosed persons and excludes those who do not have a condition). Classification criteria are often used for diagnostic purposes, as the 1990 criteria have been, but this was not the purpose of their original introduction.
What Fred Wolfe intended with the 2010 criteria was to create diagnostic criteria that were more user-friendly for clinicians to use in practice— for example, reliance on the tender point exam, which we know may be incorrectly applied in practice and be misleading in suggesting that FM is primarily a muscle or tendon problem as opposed to being primarily a problem with sensitization and dysregulation of the CNS. The new criteria rely more on pattern recognition of the constellation of chronic widespread pain along with other characteristic features such as fatigue, sleep disturbance, cognitive dysfunction, and irritable bowel symptoms—symptoms that may occur either as an independent entity or in association with other chronic illnesses such as rheumatoid arthritis or osteoarthritis.
Fred’s work has shown us that there is a great deal of overlap between those who get positively identified with FM by the two criteria, but the newer criteria may be slightly more sensitive in picking up a broader group of patients that the clinician can then evaluate further to delineate how much of their symptom complex is due to FM and how much is due to coexistent conditions, and then treat appropriately.
Who Manages Fibromyalgia Patients?
Medscape: How familiar and/or comfortable do you think primary care clinicians are with making an FM diagnosis? Or do you feel it is more the domain of pain specialists and rheumatologists?
Dr Clauw: I think practicing primary care physicians (PCPs) are much more comfortable in both diagnosing and treating FM than they once were. If they are not comfortable, most subspecialists are very willing to see a patient a single time and confirm that FM is the correct diagnosis— and it is reasonable to send patients to whatever subspecialist they think can best make that distinction given the patient’s predominant symptoms (eg, rheumatologist if the presentation is primarily musculoskeletal; neurologist if the symptoms mimic multiple sclerosis).
Regarding treatment, subspecialists often have nothing additional to offer that PCPs cannot do, which is why most of us encourage PCPs to treat these patients themselves. Otherwise the patients will often get procedures that are not helpful or get put on classes of drugs (ie, opioids) that are not helpful.
Dr Mease: I suspect that PCPs vary considerably in their comfort and confidence in diagnosing and treating FM. I would agree with Dan that more and more of the PCPs I speak with or lecture to are growing savvier about understanding the neuroscience behind FM, willing to have less stigma about considering the diagnosis, and garnering experience with use of nonnarcotic neuromodulatory medicines and nonpharmacologic approaches to treating FM.
However, there are broad swaths of PCPs who have not become educated about our current understanding of the pathogenesis of FM, are clueless about current treatment approaches, and/or maintain a generally negative attitude toward anything related to FM. This is also true for some of the subspecialists in rheumatology and neurology, so you cannot always count on a considerate evaluation from these subspecialists.
I don’t think it is simply a matter of PCP vs subspecialist but rather a matter of having enough clinicians who have become educated and experienced with treatment potential to be willing to evaluate and treat FM patients. The assessment and treatment are not complicated or risky, so they can be readily accomplished by a savvy PCP.
The Latest in Management
Medscape: Given the most recent evidence, how do you currently approach treating FM patients?
Dr Clauw: Both drug and nondrug therapies can be very effective in treating FM, and in fact, most experts believe that the best approach is to combine the two different types of therapies because they are probably working on different aspects of the disorder.
The three classes of drugs with the best evidence are tricyclics (TCAs—cyclobenzaprine, amitriptyline), serotonin-norepinephrine reuptake inhibitors (SNRIs— duloxetine and milnacipran), and gabapentinoids (gabapentin and pregabalin). Only about a third of individuals will have a meaningful improvement with any of these classes of drugs, probably because FM can be due to abnormalities in many different neurotransmitter systems that are known to regulate pain perception, sleep, mood, and alertness.
Second-tier drug classes include higher doses of older SSRIs (sertraline, paroxetine, and fluoxetine become more noradrenergic at higher doses whereas this is not the case with citalopram or escitalopram), low-dose naltrexone, cannabinoids, and gamma hydroxybutyrate. In general, with both drug and nondrug therapies, a “start low, go slow” approach is best to avoid side effects. To improve tolerability, taking TCAs several hours before bedtime can be helpful, as can taking SNRIs with food to reduce the common side effect of initial nausea (which, as patients should be counseled, typically resolves). Similarly, the gabapentinoids are often better tolerated if they are given primarily or exclusively at bedtime.
Dr Mease: I would agree that creative combinations of approaches, using both medication and nonmedication approaches, as mentioned by Dr Clauw, are optimal for treating the symptoms of FM. Keep in mind that we are aiming to improve a number of different symptoms, including pain, fatigue, sleep disturbance, and impaired cognition, to name a few, so it is likely that no single approach will address all of these symptom domains or do so fully. Thus, we need to combine medicinal and nonmedicinal approaches.
For example, one approach may help pain but not fatigue, and another may be the opposite, so it is optimal to combine the two. Also, it is important for a patient to not expect that any therapy will completely improve symptoms. Having unrealistic expectations for breadth and depth of symptom control can lead to disappointment and frustration as well as excessive doctor- and treatment-shopping. I usually take a little time to explain, in lay terms, our current understanding of the pathophysiology of FM and then bridge to how these treatments affect that biology in a favorable way. This also allows me to explain how some drugs, such as narcotic pain medicines, may unfavorably influence the pathophysiology of FM.
Dr Clauw: The nondrug treatments that have the best evidence for efficacy are education, exercise, and cognitive-behavioral therapy (CBT). FibroGuide is a free CBT program for FM patients that has been shown to be effective in a clinical trial and can give patients access to CBT treatments to which they might not otherwise have access. Other treatments that can be effective include yoga, tai chi, acupuncture, and many other complementary and alternative medicine therapies.
Dr Mease: PCPs and allied health personnel such as nurse practitioners and physician assistants are in an ideal position to both identify and treat FM. They are seeing patients more often, know them in a holistic way, and have training about care of the individual in a family and psychosocial context. The optimal way to involve rheumatologists or other specialist physicians in FM care is for the purpose of ruling out other conditions that may be coexistent with or mimicking FM, such as early rheumatoid arthritis or lupus, which would benefit from treatment specific for those conditions. In addition, such specialists may have more insight about the array of available treatment options and experience with creative combinations tailored to the patient’s particular symptom complex. Recommendations can be fed back to the PCP for ongoing care, with perhaps occasional review by the specialist. This model of care is going to become increasingly pertinent with healthcare reform.