Reviewing the pathophysiology, prevalence and impact of fibromyalgia, these authors also offer pertinent insights on the array of medications and other modalities clinicians can use to treat symptoms of the condition.

Download "A Guide To Common Medications For FM Symptoms" in PDF format

Fibromyalgia (FM) is a common, costly and sometimes highly debilitating chronic illness. Fibromyalgia affects an estimated 11 million people in the United States and 80 to 90 percent are women.1 Researchers are now proposing that fibromyalgia be classified as a disease rather than a syndrome because the primary symptom of pain is no longer serving its physiologic purpose.2

People with FM report widespread musculoskeletal pain (100 percent), fatigue (96 to 100 percent) and disturbed sleep (86 to 98 percent). Common coexisting syndromes include restless leg syndrome, chronic low back pain, irritable bowel syndrome, mood disorders, temporomandibular joint disorder, chronic tension type headaches, multiple chemical sensitivities, chronic pelvic pain, irritable bladder, exercise induced pain and fatigue, and neurally mediated hypotension.3 Clinicians can treat each of these symptoms or coexisting syndromes in order to help maximize the quality of life in patients with FM. In our FM practice, we use standardized questionnaires to screen for symptoms of each of the common coexisting disorders. Our complete first visit questionnaire is avaiable on the Web site http://www.myalgia.com/Paintools/Initial%20
Visit%20Questionnaire%201102.pdf

Figure 1

Unfortunately, there is not a single FDA-approved drug indicated for the treatment of FM. In order to maximize symptom management of FM, clinicians must take a careful history and treat coexisting syndromes as well as the primary complaints. Accordingly, let us take a closer look at this condition.

Defining Fibromyalgia
Rigorous diagnostic guidelines for FM were determined in multicenter testing over a decade ago. By definition, people with FM must have widespread pain in at least three of four body quadrants for at least three consecutive months and localized pain on palpation in at least 11 of 18 selected muscle-tendon junctions (which are referred to as tender points). For a listing of the aforementioned diagnostic tender points, see Figure 1.4 Pain is considered widespread when the patient has pain in both sides of the body; pain above and below the waist; and axial skeletal pain in either the cervical spine, anterior chest, thoracic spine or low back pain, which is considered lower segment pain.

Assessing The Prevalence And Impact Of FM
Increased recognition of FM in both primary care and rheumatology clinics has skyrocketed since the publication of the ACR’s FM classification criteria in 1990. Medline references for FM soared and so did NIH funding as evidenced by the number of projects involving FM. From 1975 to 1990, there were only 17 projects. From 1992 to the present, there have been 500 projects involving FM. Diagnostic criteria also set the stage for epidemiological studies, demonstrating that FM in the general population has a prevalence ranging from 1.3 to 7.3 percent.5-10

FM carries an annual direct cost of care over $20 billion.11-13 People with FM account for a large proportion of rheumatology outpatient visits and FM is the second or third most common diagnosis made by British rheumatologists.14-16 In a cross-sectional mail survey of Canadian rheumatologists, FM was listed as one of the three most common diagnoses among their patients.17 In an Israeli internal medicine ward, 15 percent of the inpatients were found to have FM and FM in hospital patients could be more common than reported findings.18 Other studies have found a significant occurrence of FM in concurrence with other diseases. Among outpatients, there was a 44 percent occurrence of FM in patients with primary Sjogren’s, a 30 percent occurrence in patients with systemic lupus erythematosus and an 18 percent occurrence in patients with rheumatoid arthritis.19-21 If health care providers do not recognize this association in their patients, they may embark on a line of inappropriate and potentially dangerous treatment (e.g. steroids, chemotherapeutics).

People with FM have no outward manifestations and may appear in normal health. However, studies have shown many of those with FM have difficulty remaining competitive in the workforce.22-24 Most people with FM report that chronic pain and fatigue adversely affect the quality of their life and negatively impact their vocational abilities.25-28 According to a survey of patients being treated for FM in American academic centers, 70 percent perceived themselves as being disabled. Sixteen percent were receiving Social Security benefits. This compares to 2.2 percent in the general US population.29

Understanding The Pathophysiology
Over the past two decades, fibromyalgia has risen out of a cloud of psychosomatic suspicion due to objective findings in chronic pain, resulting in a preponderance of evidence about the existence of FM.30-33
The primary dysfunction is central sensitization. This is a pathophysiological abnormality of the central nervous system in which sensory impulses are amplified at the level of the spinal cord. Impulses are “gated” at this level by changes in the sensitivity of dorsal horn neurons directly and indirectly via descending pathways from the brainstem.33 During central sensitization, peripheral pain nerves (nociceptors), such as those in skeletal muscles, are repeatedly stimulated by stretching or pressure. They can become sufficiently sensitized to cause the release of pain mediating neurotransmitters in the spinal cord (e.g. Substance P). The resulting nerve impulses are carried to the central nervous system where “central sensitization” reduces the pain threshold, increases nociceptor response to painful stimuli, increases the duration of pain after the stimulation and results in an expansion of the receptive fields for pain.34

Some key studies have identified central sensitization in FM and abnormal pain processing (see "What Studies Reveal About Abnormal Pain Processing In FM" on page 20).35-55 One may view these studies with hope and validation. Clinicians can tell people with FM that researchers can now measure and see their pain. They can also tell these patients that research efforts are currently focused on treatments to reverse symptoms and someday even prevent FM.

Key Diagnostic Pointers
When it comes to FM, few other diseases present with as much new onset widespread body pain in people younger than 70. The true mimicking conditions of FM are severe hypothyroidism, several types of cancer, osteomalacic myopathy and hepatitis C. Nevertheless, in order to rule out other diagnoses, it is reasonable to obtain the following labs: CBC without differential, chemistry panel, hepatitis C, sedimentation rate, TSH and vitamin D-25. In regard to TSH and vitamin D-25, one would especially want to consider these labs if your practice is north of the line connecting Atlanta to Los Angeles, if the patient is elderly or if he or she has difficulty converting vitamin D from the skin or extracting it from the gut. Any abnormalities in these labs should be credited to another diagnosis other than FM. It is also noteworthy that people with FM experience pain and stiffness in their joints but they should never have objective synovitis. When patients present with a history or findings of redness or swelling of their joints, clinicians should screen them for other specific types of arthritis.

Essential Treatment Considerations
When it comes to milder cases of FM, clinicians can easily manage these patients with low dose pain and sleep medications, exercise and minimal behavioral strategies. However, other people may have a more pronounced course and a series of frustrating and often disappointing office visits. They eventually apply for and receive social security and disability benefits. When treating these patients, we usually begin with education and subsequently consider appropriate medications, cognitive, physical and occupational therapies, and exercise.

There are FDA approved drugs and non-pharmacologic treatments for each of these coexisting problems. For a list of medications that we commonly use in our practice, see “A Guide To Common Medications For FM Symptoms” on pages 18 and 19.56-77 However, keep in mind that some drugs may treat more than one symptom. A recent JAMA review reveals more randomized trials with tricyclic antidepressants for FM than any other class of drugs. Unfortunately, these agents often have a poor side effect tolerance including sicca syndrome, constipation, morning hangover and weight gain.

Due to the central sensitization effect, clinicians often need to initiate medication at a lower dosage and gradually increase it. Doing so decreases the amplification of side effects. When a patient brings you a list of medications that he or she is sensitive or “allergic” to, consider the possibility that the patient may be having an increased side effect due to central sensitization. Often patients can tolerate a lower dose initially that is titrated up slowly.

In regard to the aforementioned list of medications, it is not a comprehensive list. For example, agents currently being tested for FM do not appear. Some of the most promising agents include second-generation monoamine oxidase inhibitors that are applied transdermally, a dual reuptake inhibitor called Milnacipran, and MK0677, an oral growth secretagogue.

Pain is the primary and defining symptom of fibromyalgia. We use the World Health Organization’s pain ladder, which ranges from nonscheduled medications and schedule II short acting narcotics to schedule III long acting narcotics (both oral and transdermal) and methadone. When a patient has breakthrough pain, we sometimes use short acting narcotics in addition to long acting agents. Sometimes these patients will have pain that feels like superficial burning, pinpricking or skin sensitivity types of pain. Occasionally, these symptoms are confused with carpal tunnel syndrome or restless leg syndrome. In the case of carpal tunnel syndrome, patients may wake up at night with these symptoms and the symptoms are subsequently confirmed with nerve conduction testing.

Common coexisting syndromes with fibromyalgia include chronic low back pain and exercise induced pain and fatigue.

It is important to understand the difference between drug dependency and drug addiction when prescribing scheduled agents. Drug addicts use the drug to get high or escape life. Drug dependent patients need to understand that stopping their medications abruptly can cause undesirable side effects. Appropriate use of scheduled drugs will be manifested by increased functional abilities and enhanced vocational/avocational activities.

How Insomnia And Fatigue Factor Into Fibromyalgia
Insomnia is a chronic disorder and may include difficulty falling asleep (sleep latency), staying asleep or both. Perturbed sleep was in fact the first objective finding in FM.78 Accordingly, clinicians know that treating sleep problems is important in the overall management of FM symptoms. Poor sleep is a leading cause of fatigue. People with FM do not usually have other sleep disorders such as narcolepsy or cataplexy but may have sleep apnea and often have restless leg syndrome. Between 30 to 60 percent of FM patients have restless leg syndrome.

Medications for insomnia fall into at three main categories: sedating antidepressants, nonbezodiazepine hypnotics and antihistamine drugs. Some patients get further sleep improvement by adding over the counter sedating antihistamines like diphenhydraminine (Benadryl) or doxylamine succinate (Unisom). When treating patients with FM, one should consider having all male patients and all overweight or obese female patients undergo a sleep study One diagnostic pearl in FM is to consider a sleep study on all males and all overweight/obese females with FM. These people are more likely to have concurrent sleep apnea than other patients with FM. Sleep apnea usually requires treatment with CPAP. Clinically, we note improvements in fatigue when sleep apnea is treated but only minimal improvements in other FM symptoms such as pain. Further detail can be found in a recent, excellent overview of insomnia by Zunkel in Clinician Reviews.79

What About The Role Of Cognitive Therapies?
Most people with FM report relief when the mysterious symptoms are given a name. White and colleagues confirmed that labeling someone with FM does not increase health care seeking behavior but, in fact, results in better treatment and there is an improvement in the quality of life.80 Given the chronic nature of FM, people need cognitive behavioral therapy (CBT) counseling to minimize pain and fatigue. CBT includes pacing, fatigue control, setting boundaries and establishing realistic expectations for vocational and avocational activities given the chronicity and severity of the patient’s specific course of FM. When an existential crisis occurs, psychiatric mental health nurse practitioners and psychologists specializing in chronic illness management can be of great assistance during this transition. Lastly, clinicians can refer patients with FM to helpful Web sites, books and periodicals.

Emphasizing Exercise
Exercise is essential to maximize symptom management in FM. People who gently exercise two to five times a week report a 25 percent reduction in the overall symptomatology of FM and often require less prescription medication.24,81 Unfortunately, people with FM have intense pain with exercise. This is perhaps due in part to muscle microtrauma made worse by inadequate growth hormone release during exercise.82 A traumatized muscle sends nerve impulses to the spinal cord and these impulses are amplified by central sensitization. People with FM may interpret muscle soreness as pain.

Patients can modify their exercise. When they perform eccentric muscle work, there is a reduced overall stretch on the muscle fibers. For example, lowering a heavy object in the hands involves eccentric action of the biceps. To minimize eccentric contraction of the bicep, one can slowly lift a hand weight to a count of six and then lower it more quickly with a count of three. Then the patient needs to completely unload the muscle (drop the weight) in order to allow for a delayed return to a resting baseline state.83 All 12 major muscle groups can be tailored to minimize eccentric work.

Since muscle work occurs during activities of daily living, people with FM can perform eccentric muscle work by taking smaller steps when walking downhill, using short strokes when vacuuming or sweeping and placing the body’s midline near any object they are lifting or manipulating. However, people with FM need to stretch all major muscle groups to a point of gentle tension, not pain, several times a day. Likewise, they should also correct their head forward body position. Many people with chronic pain assume a rounded pain posture position and need to remind themselves to occasionally breath deeply from the diaphragm and “open up the chest.” Deep breathing may also reverse the oxygen deficit muscles and decreases stress.

In addition to stretching and minimizing the potential of microtrauma in eccentric work, people need some form of aerobic exercise. Unfortunately, many people with FM also have lower body pain syndromes such as plantar fasciitis, ankle tendonitis or knee or hip osteoarthritis. For these people, performing aerobic exercise in a chair or in water may be preferable. However, the exercises should minimize repetition, overhead work and allow for a 50 percent reduction in intensity, especially during a pain flare. For more specific exercises for patients with FM, please visit http://www.myalgia.com/.

Final Notes
FM is an identifiable and easily diagnosed disease. While there are several medications for managing symptoms in FM, no single agent predictably improves all symptoms in all patients. Clinicians must carefully rule out other causes of chronic widespread pain, look for common coexisting syndromes and maximize treatment with both pharmacologic and non-pharmacologic treatment. In the next decade, we may see more targeted, effective medications as the pathophysiologic cloth of FM continues to be unraveled.