Men with fibromyalgia often go undiagnosed, Mayo Clinic study suggests

Fibromyalgia is a complex illness to diagnose and to treat. There is not yet a diagnostic test to establish that someone has it, there is no cure and many fibromyalgia symptoms—pain, fatigue, problems sleeping and memory and mood issues—can overlap with or get mistaken for other conditions. A new Mayo Clinic study suggests that many people who have fibromyalgia, especially men, are going undiagnosed. The findings appear in the online edition of the journal Arthritis Care & Research.

27 dec 2012--More research is needed, particularly on why men who reported fibromyalgia symptoms were less likely than women to receive a fibromyalgia diagnosis, says lead author Ann Vincent, M.D., medical director of Mayo Clinic's Fibromyalgia and Chronic Fatigue Clinic.

"Health care providers may not think of this diagnosis when face to face with a male patient with musculoskeletal pain and fatigue," Dr. Vincent says. "These findings need to be explored further."

Researchers focused on Olmsted County, Minn., home to a comprehensive medical records pool known as the Rochester Epidemiology Project, and used multiple methods to try to get at the number of people over age 21 with fibromyalgia.

They used the epidemiology project to identify just over 3,000 patients who looked like they might have fibromyalgia: Roughly a third had a documented fibromyalgia diagnosis. That amounted to 1.1 percent of the county's population 21 and older.

In the second method, researchers randomly surveyed Olmsted County adults using the American College of Rheumatology's fibromyalgia research survey criteria. The criteria include the hallmarks of fibromyalgia: widespread pain and tenderness, fatigue, feeling unrested after waking, problems with memory or thinking clearly and depression or anxiety, among other symptoms. Of the 830 who responded to the survey, 44, or 5.3 percent, met those criteria, but only a dozen had been diagnosed with fibromyalgia.

Based on the study's findings, the researchers estimate that 6.4 percent of people 21 and older in Olmsted County have fibromyalgia—far more than have been officially diagnosed with it.

Fibromyalgia is more common in women, but men can get it too. The discrepancy between the number of people reporting fibromyalgia symptoms and the number actually diagnosed with the condition was greatest among men, the study found. Twenty times more men appeared to have fibromyalgia based on their survey response than had been diagnosed, while three times more women reported fibromyalgia symptoms than were diagnosed.

"It is important to diagnose fibromyalgia because we have effective treatments for the disorder," says co-author Daniel Clauw, M.D., director of the University of Michigan Health System Chronic Pain & Fatigue Research Center.

Studies also show that properly diagnosing people with fibromyalgia reduces health care costs, because they often need far less diagnostic testing and fewer referrals looking for the cause of their pain, Dr. Clauw says.

More information: onlinelibrary.wile… 896/abstract

Provided by Mayo Clinic

Yoga alleviates pain and improves function in fibromyalgia patients

According to new study published in Pain

Philadelphia, PA, 25 oct 2010– Fibromyalgia (FM) is a debilitating condition affecting 11 million individuals in the US alone. FM carries an annual direct cost for care of more than $20 billion and drug therapies are generally only 30% effective in relieving symptoms and 20% effective in improving function. Standard care currently includes medications accompanied by exercise and coping skills approaches. In a study published in the November issue of PAIN, researchers report patients participating in a "Yoga of Awareness" program showed significantly greater improvement in FM symptoms and functioning compared to patients on a standard FM care program.

"Although yoga has been practiced for millennia, only recently have researchers begun to demonstrate yoga's effects on persons suffering from persistent pain," commented lead investigator James W. Carson, PhD, Oregon Health & Science University. "The Yoga of Awareness program stands in contrast to previous multimodal interventions with FM patients in that it integrates a wide spectrum of yoga-based techniques – postures, mindfulness meditation, breathing exercises, application of yogic principles to optimal coping, and group discussions.…the findings of this pilot study provide promising preliminary support for the beneficial effects of yoga in patients with FM."

Given the much higher prevalence of FM in females (80%), researchers chose to include only women in this study. 53 women at least 21 years of age participated. To be eligible, patients had to meet the following criteria: be diagnosed with FM by American College of Rheumatology (ACR) criteria for at least 1 year and be on a stable regimen of pharmacologic and/or non-pharmacologic treatment for FM for at least 3 months. The patients were randomized; 25 participated in the Yoga of Awareness program, while 28 received standard care.

Yoga of Awareness is an innovative, comprehensive yoga program, which for the purposes of this study was tailored to address pain, fatigue, sleep disturbance, and emotional distress in FM. Each Yoga of Awareness class included approximately 40 minutes of gentle stretching poses, 25 minutes of mindfulness meditation (e.g., awareness of breath, awareness of awareness itself), 10 minutes of breathing techniques (e.g., full yogic breath, breathing into sensation), 20 minutes of didactic presentations on the application of yogic principles to optimal coping, and 25 minutes of group discussions (e.g., experiences while practicing yoga at home).

After the yoga program was completed, both groups were assessed for fibromyalgia symptoms and functional deficits, overall improvement in fibromyalgia symptoms, physical tests of fibromyalgia symptoms and functional deficits such as tender points, strength and balance deficits, and a number of pain coping strategies.

Following treatment, women assigned to the yoga program showed significantly greater improvements on standardized measures of FM symptoms and functioning, including pain, fatigue, and mood, and in pain catastrophizing, acceptance, and other coping strategies.

Dr. Carson and colleagues observed, "In addition, the results suggested the yoga intervention led to a beneficial shift in how patients cope with pain, including greater use of adaptive pain coping strategies (i.e., problem solving, positive reappraisal, use of religion, activity engagement despite pain, acceptance, relaxation) and less use of maladaptive strategies (i.e., catastrophizing, self-isolation, disengagement, confrontation)."

The Fibromyalgia Controversy

Doctor offers unbiased overview in new book

09 june 2009--As many as fifteen million American women suffer from a disabling medical condition known as fibromyalgia. In the medical community, sides have been drawn over whether fibromyalgia is a genuine syndrome or a catchall diagnosis based on vague clinical criteria. In THE FIBROMYALGIA CONTROVERSY (Prometheus Books, $18.95), M. Clement Hall, MD presents an unbiased overview of the fibromyalgia situation today and reviews the most up-to-date opinions and studies on this condition and its surrounding controversy.

Fibromyalgia—affecting approximately five percent of the American population, mostly women—is characterized primarily by widespread pain, tender spots, decreased pain threshold, sleep disturbance, fatigue, and psychological distress. It is a chronic condition characterized by a pattern of vague symptoms that are difficult to diagnose and treat. The controversy among doctors is whether or not there is an actual disease that can be cured, rather than just a set of symptoms to manage.

"Despite being recognized as a diagnosable disease by the American College of Rheumatology, the Food and Drug Administration and most insurers, fibromyalgia has not completely shed the stigma of being dismissed as "psychosomatic" by some in the medical establishment." noted the Sacramento Bee in a May 31, 2009 article on patients not being taken seriously by their doctors. There are few conditions about which the medical profession is so polarised One side argues, sometimes heatedly, that patients are masquerading—pretending a disability they know they do not have. The other side counters, with equal passion, that fibromyalgia sufferers are abused by a society that fails to give them the support they deserve while painfully suffering from this severely debilitating illness.

In THE FIBROMYALGIA CONTROVERSY, Dr. M. Clement Hall presents six fictional, though factually based, case studies of typical patients from differing socioeconomic backgrounds and describes the varying investigations, diagnoses, and treatments they have undergone. Each of these case studies represents a composite of many years of clinical practice rather than one specific patient. Collectively, they cover the range of experiences fibromyalgia patients are likely to have encountered. By taking this unique approach, Dr. Hall presents an objective overview of the fibromyalgia situation today in North America. Patients, family members, and physicians will see themselves reflected in the descriptions and will gain a broader understanding of this challenging illness.

"While several books address the challenges of living with fibromyalgia... Hall's is a uniquely objective account that surveys diagnosis, treatments, and the controversy surrounding the condition," says Rebecca Raszewski, University of Illinois at Chicago, in a Library Journal review. "Hall... delivers a balanced view... by presenting perspectives of skeptics who doubt whether fibromyalgia is a real medical condition—as well as comprehensive descriptions of the disorder and treatment options."

By detailing the process by which clinicians make their diagnoses, explaining how those who think they may have fibromyalgia can make the most of their doctors' visits, discussing various treatments in current use (medication, physical therapy, diet modification, and alternative approaches such as massage or acupuncture), and looking at the historical record of various related disorders, Hall provides an unbiased, indispensable survey of data and views on this illness.

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THE FIBROMYALGIA CONTROVERSY is a must read for sufferers, clinicians, and those interested in gaining insight about this heated dispute in the medical community and its long-term repercussions.

About the Author: M. Clement Hall, MD (Toronto, Ontario, Canada), is the director of continuing education in the emergency department of Scarborough Hospital, and is the author of "Trauma Surgeon" among other works.

Fibromyalgia can no longer be called the 'invisible' syndrome

Molecular imaging uncovers evidence that symptoms are related to functional brain abnormalities, according to article in the Journal of Nuclear Medicine

Reston, Va., 04 nov 2008—Using single photon emission computed tomography (SPECT), researchers in France were able to detect functional abnormalities in certain regions in the brains of patients diagnosed with fibromyalgia, reinforcing the idea that symptoms of the disorder are related to a dysfunction in those parts of the brain where pain is processed.
"Fibromyalgia is frequently considered an 'invisible syndrome' since musculoskeletal imaging is negative," said Eric Guedj, M.D., and lead author of the study. "Past imaging studies of patients with the syndrome, however, have shown above-normal cerebral blood flow (brain perfusion) in some areas of the brain and below-normal in other areas. After performing whole-brain scans on the participants, we used a statistical analysis to study the relationship between functional activity in even the smallest area of the brain and various parameters related to pain, disability and anxiety/depression."
In the study, which was reported in the November issue of The Journal of Nuclear Medicine, 20 women diagnosed with fibromyalgia and 10 healthy women as a control group responded to questionnaires to determine levels of pain, disability, anxiety and depression. SPECT was then performed, and positive and negative correlations were determined.
The researchers confirmed that patients with the syndrome exhibited brain perfusion abnormalities in comparison to the healthy subjects. Further, these abnormalities were found to be directly correlated with the severity of the disease. An increase in perfusion (hyperperfusion) was found in that region of the brain known to discriminate pain intensity, and a decrease (hypoperfusion) was found within those areas thought to be involved in emotional responses to pain.
In the past, some researchers have thought that the pain reported by fibromyalgia patients was the result of depression rather than symptoms of a disorder. "Interestingly, we found that these functional abnormalities were independent of anxiety and depression status," Guedj said.
According to Guedj, disability is frequently used in controlled clinical trials to evaluate response to treatment. Because molecular imaging techniques such as SPECT can help predict a patient's response to a specific treatment and evaluate brain-processing recovery during follow-up, it could prove useful when integrated into future pharmacological controlled trials.
"Fibromyalgia may be related to a global dysfunction of cerebral pain-processing," Guedj added. "This study demonstrates that these patients exhibit modifications of brain perfusion not found in healthy subjects and reinforces the idea that fibromyalgia is a 'real disease/disorder.'"
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, fibromyalgia syndrome is a common and chronic disorder characterized by widespread muscle pain, fatigue and multiple tender points. Tender points are specific places—for example, on the neck, shoulders, back, hips, and upper and lower extremities—where people with fibromyalgia feel pain in response to slight pressure. The syndrome is one of the most common causes of musculoskeletal pain and disability and affects three to six million, or as many as one in 50, Americans. Between 80 and 90 percent of those diagnosed are women.
Although fibromyalgia is often considered an arthritis-related condition, it does not cause inflammation or damage to the joints, muscles or other tissues. Like arthritis, however, the significant pain and fatigue caused by fibromyalgia can interfere with a person's ability to carry out daily activities.
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Coauthors of "Clinical Correlate of Brain SPECT Perfusion Abnormalities in Fibromyalgia" include Eric Guedj, Serge Cammilleri and Olivier Mundler, Service Central de Biophysique et de Médecine Nucléaire, AP-HM Timone; Jean Niboyet, Patricia Dupont, Eric Vidal and Jean-Pierre Dropinski, Unité d'Etude et de Traitement de la Douleur, Clinique La Phocéanne, all of Marseille, France.
About SNM
SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today's medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.
SNM's more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snm.org.

FDA Approves Duloxetine (Cymbalta) for Fibromyalgia

By Peggy Peck
INDIANAPOLIS, 17 june 2008-- The FDA has approved duloxetine (Cymbalta), a serotonin-norepinphrine reuptake inhibitor, for fibromyalgia, the drug-maker said today.
The Lilly antidepressant Duloxetine is the second drug to be approved for this indication. A year ago the FDA approved the seizure drug pregabalin (Lyrica) for fibromyalgia.Duloxetine is also indicated in adults for major depressive disorder, general anxiety, and peripheral diabetic neuropathy.
The added indication was approval on the basis of data from two three-month clinical trials of 874 fibromyalgia patients. In both studies, compared with placebo, duloxetine was associated with more than a 30% reduction in pain as measured by the Brief Pain Inventory (BPI) 24-hour average pain scale.
Moreover, patients randomized to duloxetine reported significant pain relief during the first week of treatment.
In both studies the majority of duloxetine patients -- 65% in one study and 66% in the other -- said they felt better since beginning treatment with 60 mg of duloxetine daily, as measured by a self-assessment (Patient Global Impression of Improvement).
The most commonly reported adverse events were nausea, dry mouth, constipation, decreased appetite, sleepiness, increased sweating, and agitation. Twenty percent of duloxetine patients discontinued the study drug because of adverse events versus 12% of placebo patients.
Duloxetine should not be taken by patients who are using or have recently used a monoamine oxidase inhibitor, patients taking thloridazine (Mellari) or patients with uncontrolled glaucoma. Severe and sometimes fatal liver problems have been reported among patients taking duloxetine. Duloxetine may increase the risk of hemorrhage among patients taking NSAIDs, aspirin, or other blood thinners.

Fibromyalgia Is Not a Rheumatologic Disease Anymore

George T. Griffing, MD
Think of your last patient with difficult-to-treat fibromyalgia: Aren't they all? Did you refer that person to a rheumatologist?
Since the 1950s, when it was first described by Dr. Graham, "fibrositis" or fibromyalgia was thought to be a rheumatologic disorder because it was characterized by musculoskeletal pain similar to other rheumatologic diseases.[1]
In 1990, The American College of Rheumatology established diagnostic criteria based on the scoring of 18 potential tender points.[2] It turns out, however, that these tender points have nothing to do with fibromyalgia. Biopsy of the tender points shows no pathologic changes, and numerous studies have not shown any abnormalities in the musculoskeletal tissues that are painful.
Current evidence points to a neurologic disorder of central pain processing.[3] Fibromyalgia patients experience pain differently and have lower pain thresholds compared to normals. Research has demonstrated that various pain-related processes in the brain and spinal cord are abnormal in fibromyalgia.[4] But more work remains to be done.
Market surveys show the number one class of drugs used to treat fibromyalgia is nonsteroidal anti-inflammatory drugs.[5] Since fibromyalgia is not an inflammatory disease, it is not surprising we have a lot of treatment failures.
The pharmaceutical industry knows this, and they are viewing fibromyalgia as the prototypical central pain state. The 2 main drug classes of interest are the dual receptor reuptake inhibitors, like duloxetine or Cymbalta, and the antiepileptic drugs, like pregabalin or Lyrica. In fact, pregabalin has shown enough efficacy, that it is the first and only drug approved by the FDA for the treatment of fibromyalgia.[6]
Therefore, in the future, with new insights and therapies on the horizon, we will no longer need to refer our fibromyalgia patients to the rheumatologist.
That's my opinion. I'm Dr. George Griffing, Professor of Medicine at St. Louis University and Editor-in-Chief of Internal Medicine for eMedicine.

References
Graham W. The fibrositis syndrome. Bull Rheum Dis. 1953;3:33-34.
Wolfe F, Symthe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172.
Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative review: the pathophysiology of fibromyalgia. Ann Intern Med. 2007;146:726-734.
Clauw DJ. Fibromyalgia: update on mechanisms and management. J Clin Rheumatol. 2007;13:102-109.
Rooks DS. Fibromyalgia treatment update. Curr Opin Rheumat. 2007;19:111-117.
Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52:1264-1273.

Appropriate Exercise, Patient Education May Be Helpful for Fibromyalgia

November 19, 2007 — Progressive walking, simple strength training, and stretching improved functional status, key symptoms, and self-efficacy in women with fibromyalgia actively treated with medication, according to the results of a randomized controlled trial reported in the November 12 issue of the Archives of Internal Medicine.
"Self-management has increasingly been recommended as part of standard care for fibromyalgia, a common, poorly understood condition with limited treatment options," write Daniel S. Rooks, ScD, from the Beth Israel Deaconess Medical Center in Boston, Massachusetts, and colleagues. "Data that assess popular self-management recommendations are scarce. We evaluated and compared the effectiveness of 4 common self-management treatments on function, symptoms, and self-efficacy in women with fibromyalgia."
From September 16, 2002, through November 30, 2004, a total of 207 women with confirmed fibromyalgia were recruited and randomized to receive 16 weeks of aerobic and flexibility exercise (AE); strength training, aerobic, and flexibility exercise (ST); the Fibromyalgia Self-Help Course (FSHC); or a combination of ST and FSHC (ST-FSHC). The main endpoint was change in physical function from baseline to completion of the 16-week intervention; secondary endpoints were social and emotional function, symptoms, and self-efficacy.
The mean Fibromyalgia Impact Questionnaire score improved by −12.7 in the ST-FSHC group, −8.2 in the AE group, −6.6 in the ST group, and −0.3 in the FSHC group. Compared with the FSHC group, the ST-FSHC group had greater improvement (mean difference, −12.4; 95% confidence interval [CI], −23.1 to −1.7).
Physical function scores on the 36-Item Short-Form Health Survey improved to a similar extent in the ST-FSHC (mean difference, 13.6; 95% CI, 2.3 - 24.9) and AE groups (mean difference, 13.1; 95% CI, 1.6 - 25.6). On the 36-Item Short-Form Health Survey, bodily pain scores improved in the ST-FSHC (14.8), AE (13.2), and ST (5.7) groups, as did social function, mental health, fatigue, depression, and self-efficacy. Benefits on physical function of exercise alone and combined with education were maintained at 6 months.
"Progressive walking, simple strength training movements, and stretching activities improve functional status, key symptoms, and self-efficacy in women with fibromyalgia actively being treated with medication," the study authors write. "The benefits of exercise are enhanced when combined with targeted self-management education. Our findings suggest that appropriate exercise and patient education be included in the treatment of fibromyalgia."
Limitations of the study include absence of a control group that received no intervention and dropout of approximately one third of the overall sample.
"The findings of this study contribute to the growing body of knowledge on the benefits of exercise and physical activity for improving the health and function of adults with chronic illness," the study authors conclude. "People with rheumatic conditions are even less active than the relatively sedentary general public. Future studies are needed to identify ways of integrating appropriate exercise into the treatment plans of people with fibromyalgia and other chronic illnesses and to promote the adoption and maintenance of a more physically active lifestyle."
The Arthritis Foundation and National Institutes of Health supported this study. Dr. Rooks is now employed by the Novartis Institutes for Biomedical Research, Inc, Cambridge, Massachusetts. Four of the study authors have received funding from the Arthritis Foundation and National Institutes of Health. The remaining study authors have disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:2192-2200

Exercise and Education a Boost to Women With Fibromyalgia
BOSTON, Nov. 13 -- Fibromyalgia functional symptoms and pain respond to a program of walking, strength training, and stretching, according to researchers here.
Action Points
Explain to patients who ask that for women with fibromyalgia who take medication, an exercise program of walking, strength training, and stretching, plus learning self-management skills, improved function and pain symptoms.
In addition, the benefits appeared to be enhanced when a self-management education program was added, Daniel S. Rooks, Sc.D., of Harvard, and colleagues, reported in the Nov. 12 issue of the Archives of Internal Medicine.
A randomized trial found a statistically significant improvement of 25% among women assigned to an exercise program plus a self-help course, compared with no benefit for those given only the self-help course, said Dr. Rooks, now with Novartis Institutes for Biomedical Research in Cambridge, Mass., and colleagues.
This study suggested that progressive walking, simple strength training movements, and stretching activities can improve physical, emotional, and social function, key symptoms, and self-efficacy in women with fibromyalgia being actively treated with medication, the researchers wrote.
The benefits of exercise, when combined with targeted self-management education, continued for six months after completion of the intervention, the researchers said.
Fibromyalgia affects approximately 3.4% of women and 0.5% of men in the U.S., according to the researchers. But even with the 2004 FDA approval of pregabalin (Lyrica), drug therapy is often insufficient to resolve persistent symptoms or improve functional limitations and quality of life, they wrote.
To compare the effectiveness of four common self-management treatments on function, symptoms, and self efficacy, the researchers recruited 207 women from 2002 through 2004, all taking medication. They were randomly assigned to one of four groups for 16 weeks. A total of 135 women completed the study.
The groups included aerobic and flexibility exercise; strength training added to aerobic and flexibility exercise (three-part workout); the Arthritis Foundation's Fibromyalgia Self-Help Course; or a combination of the three-part exercise program plus the self-help course.
The exercise groups met twice weekly, gradually increasing the length and intensity of workouts, with instructions to perform a third day of exercise on their own.
The seven-session self-management education program provided information about fibromyalgia, taught self-management skills in daily activities, and suggested ways to manage symptoms and incorporate wellness activities, including exercise, into daily life. Information was provided through lectures (five to 15 minutes) with group discussion and supplementary readings.
All exercise programs lasted about 60 minutes beginning with a brief warm-up walking on a treadmill and then progressing to a self-determined level of moderate effort for a predetermined amount of time.
As measured by two self-assessment questionnaires and a performance test (the Fibromylagia Impact Questionnaire score), all exercise groups showed greater improvement in function compared with the education group, the researchers reported.
In the four groups, the improvements in the mean Fibromyalgia Impact score were:
−12.7 for the strength, aerobic, and flexibility (full exercise) group plus the education program
−8.2 for the aerobic and flexibility group alone (no strength training)
−6.6 for the three-part exercise group alone (these women divided their time between aerobic exercise, flexibility, and strength training)
−0.3 for the education group alone
Examination of the Fibromyalgia Impact total score total showed that women in the full exercise plus education group demonstrated a 25% greater improvement than the education-alone group (mean difference, −12.4, 95% confidence interval: −23.1 to −1.7).
Bodily pain scores on the 36-Item Short-Form Health Survey improved in the three-part exercise plus education group (14.8), the aerobic/flexibility group (13.2), and in the three-part exercise group (5.7).
Social function, mental health, fatigue, depression, and self-efficacy also improved in the groups that exercised.
Among the study's limitations was the fact that the study was designed not to have a group that received no intervention to minimize bias of interpersonal contact with persons in active interventions. Therefore, it was not possible to determine how an intervention group compared with no treatment.
Also about one-third of the overall sample dropped out, a rate similar to previous fibromyalgia studies that used comparable interventions.
This research was supported by an Arthritis Foundation Investigator Award and National Institutes of Health grants.
The investigators reported no financial conflicts.Primary source: Archives of Internal MedicineSource reference: Rooks, DS, et al "Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial"Arch Intern Med 2007; 167: 2192-2200.

Opioid Resistance in Fibromyalgia Explained by Receptor Function

ANN ARBOR, Mich., Sept. 27 -- The reason that opioids seem to fizzle for fibromyalgia may be because of reduced receptor activity in regions of the brain that process and dampen pain signals, researchers here found.
Reduced µ-opioid receptor-binding potential in fibromyalgia patients was also significantly correlated with depression and emotional components of pain, reported Richard E. Harris, Ph.D., of the University of Michigan, and colleagues, in the Sept. 12 issue of the Journal of Neuroscience.
"Because these receptors are the target of opiate drugs," they wrote, "a profound reduction in the concentration or function of these receptors is consistent with a poor response of fibromyalgia patients to this class of analgesics, observed anecdotally in clinical settings."
The researchers used PET with a selective µ-opioid receptor radiotracer to assess receptor availability differences between fibromyalgia patients and healthy pain-free individuals.
Their study included 17 right-handed women with fibromyalgia (mean age 44.8, mean diagnosis duration 8.4 years) and 17 age- and sex-matched healthy controls who were part of an ongoing study of acupuncture treatment. The analysis was done on PET scans and other data collected at baseline.
No participants were taking opioids or had a history of their use. Of the 17 fibromyalgia patients, 10 were taking antidepressant medication, either serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors.
The women reported "sensory" and "affective" characteristics of their pain on the Short Form of the McGill Pain Questionnaire immediately prior to undergoing the PET scan.
Depressive symptoms were self-reported on the Center for Epidemiological Studies-Depression Scale, which is used to detect major or clinical depression.
The PET scans showed significantly less opioid receptor-binding potential overall in fibromyalgia patients than in controls (P<0.01).
Fibromyalgia patients also had significantly less opioid receptor availability in four specific regions of the brain, the left and right nucleus accumbens, the left amygdala, and the right dorsal anterior cingulate (all P<0.05).
After controlling for global opioid receptor binding potential, the difference was still significant for the left (P<0.001) and right (P<0.05) nucleus accumbens and the amygdala (P<0.005). Activity in the dorsal anterior cingulate showed a similar trend (P<0.07).
"All of these regions have previously been noted to play some role in nociception and pain," Dr. Harris and colleagues said.
But, antidepressant use in the fibromyalgia group did not explain the opioid receptor abnormalities, the researchers said.
Binding potential in these four brain regions was not significantly different in fibromyalgia patients taking serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors than among those not taking drugs in this class (all P>0.35).
Fibromyalgia patients also showed more depressive symptoms (P<0.05) with reduced opioid receptor binding within the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.
Among fibromyalgia patients, reductions in opioid receptor-binding in the left nucleus accumbens was correlated with significant increases in the emotional component of clinical pain (P<0.05)>0.50). Controlling for antidepressant medication use did not change the association.
The relative amount of emotional versus sensory pain varied between patients in correlation with differences in opioid receptor binding in the dorsal anterior cingulate (P<0.05), posterior cingulate (P<0.001), and right ventral putamen (P<0.05) with a trend for the anterior cingulate (P=0.09).
"These results suggest that in fibromyalgia patients the affective quality of pain is associated with reduced µ-opioid receptor availability throughout the cingulate and other brain regions commonly associated with pain modulation," the researchers wrote.
Alterations in central opioid neurotransmission in specific brain regions "suggest that these mechanisms, possibly as a consequence of persistent pain, are involved in the clinical presentation and even the perpetuation of symptoms in this illness," they added.
Regardless of whether the mechanism is high endogenous opioids or downregulation of opioid receptors, the findings predict a poorer response to opioid painkillers for fibromyalgia patients, they concluded.
The study was supported by grants from the Department of Army, the National Institutes of Health. Dr. Harris was supported by a National Center for Complementary and Alternative Medicine grant and another researcher was likewise supported by a National Institutes of Health grant. None of the researchers reported conflicts of interest. Primary source: The Journal of NeuroscienceSource reference: Harris RE, et al "Decreased Central µ-Opioid Receptor Availability in Fibromyalgia" J Neurosci 2007;27:10000-10006.

EULAR Issues Guidelines for the Treatment of Fibromyalgia Syndrome

September 21, 2007 — The European League Against Rheumatism (EULAR) has issued the first guidelines for the treatment of fibromyalgia syndrome (FMS) and published them in the September 17 Online First issue of the Annals of the Rheumatic Diseases.
"Although effective treatments are available no guidelines exist for management of FMS," write Serena F. Carville, from King's College London, United Kingdom, and colleagues. "The objectives were to ascertain the strength of the research evidence on effectiveness of treatment of FMS and develop recommendations for its management based on the best available evidence and expert opinion to inform healthcare professionals."
The authors of these guidelines consisted of a multidisciplinary task force from 11 European countries. This panel defined the study design a priori, using standard operating procedures published by EULAR. These included search strategy, which was a systematic review using the keywords "fibromyalgia," "treatment or management," and "trial"; "participants"; "interventions"; "outcome measures"; "data collection"; and "analytical method."
Exclusion criteria for identified studies were failure to use classification criteria from the American College of Rheumatology (ACR), studies that were not clinical trials or studies comprising inclusion of patients with chronic fatigue syndrome or myalgic encephalomyelitis. The main endpoints were change in pain measured by the visual analog scale (VAS), and the fibromyalgia impact questionnaire (FIQ).
The panel categorized the studies by quality, based on whether they were randomized, blinded, and concealed allocation, and they used only the highest-quality studies as a basis for their recommendations. The panel used a Delphi process to provide a basis for recommendation when evidence from the literature was inadequate.
Of 146 studies eligible for review, 39 pharmacologic intervention studies and 59 nonpharmacologic studies were used to create the final recommendation summary tables, after those of lower quality or with insufficient data were excluded. Identified categories of treatment were antidepressants, analgesics and "other pharmacological," and exercise, cognitive behavioral therapy, education, dietary interventions, and "other nonpharmacological interventions."
Using this systematic review process and expert consensus, the panel developed 9 recommendations for the management of FMS. However, many studies reviewed had insufficient sample size and study quality to allow the panel to issue strong recommendations. EULAR plans to update the guidelines every 5 years and incorporate findings from good-quality clinical trials that will add to currently available evidence.
"These recommendations are the first to be commissioned for FMS, although previous reviews have addressed the area," the review authors conclude. "These recommendations should assist health care providers, with a secondary intention to incorporate information into materials for patients. The 9 recommendations included 8 management categories, 3 of which had strong evidence from the current literature, and 3 were based on expert opinion."
Specific recommendations in these guidelines regarding general considerations for management of FMS are as follows:
Comprehensive evaluation of pain, function, and psychosocial context is needed to understand FMS completely, because it is a complex, heterogeneous condition involving abnormal pain processing and other secondary features (level of evidence, IV D).
Optimal treatment of FMS mandates a multidisciplinary approach, which should include a combination of nonpharmacologic and pharmacologic interventions. After discussion with the patient, treatment modalities should be specifically tailored based on pain intensity, function, and associated features such as depression, fatigue, and sleep disturbance (level of evidence, IV D).
Specific recommendations on nonpharmacologic management of FMS are as follows:
Heated pool treatment, with or without exercise, is effective (level of evidence, IIa B).
For some patients with FMS, individually tailored exercise programs can be helpful. These may include aerobic exercise and strength training (level of evidence, IIb C).
For certain patients with FMS, cognitive behavioral therapy may be beneficial (level of evidence,IV D).
Based on the specific needs of the patient, relaxation, rehabilitation, physiotherapy, psychological support, and other modalities may be indicated (level of evidence, IIb C).
Specific recommendations on pharmacologic management are as follows:
Tramadol is recommended for management of pain (level of evidence, Ib A). Although other treatment options may include simple analgesics (eg, paracetamol) and other weak opioids, corticosteroids and strong opioids are not recommended (level of evidence, IV D).
Antidepressants are recommended for the treatment of FMS because they decrease pain and often improve function (level of evidence, Ib A). Appropriate options may include amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole.
Tropisetron, pramipexole, and pregabalin are recommended for the treatment of FMS because they reduce pain (level of evidence, Ib A).
Limitations of these recommendations are that some are based only on expert opinion; basis from clinical trial data limited to changes in pain measured by the VAS and function evaluated with the FIQ; failure to consider positive effects on other outcome measures of pain or on function evaluated with different instruments; and high variability in outcome measures used, results reporting, and poor methodologic quality precluding meta-analysis.
"Guidance on how to conduct good RCTs [randomized controlled trials] in FMS, including standardised outcome measures and validated, sensitive instruments is important for future research," the review authors conclude. "The assessment of strength of evidence tends to favour pharmacological studies as double blinding and placebo controls are impossible in many non-pharmacological studies. However, most non-pharmacological interventions are safe and have other health benefits."
EULAR provided financial support for creation of these guidelines. Some of the review authors have disclosed various financial relationships with Procter and Gamble, Sanofi-Aventis, Roche, Bristol Meyers Squibb, Pierre Fabre, Servier, Pfizer, Eli Lilly, Jazz Pharmaceutical, Allergan, and Wyeth.
Ann Rheum Dis. Published online September 17, 2007.

Multidimensional Approach Recommended for Fibromyalgia Treatment

July 26, 2007 — Management of fibromyalgia requires a multidimensional approach including patient education, cognitive behavioral therapy, exercise, and other treatment, according to a review published in the July 15 issue of American Family Physician.
"Fibromyalgia is an idiopathic, chronic, nonarticular pain syndrome with generalized tender points," write Sangita Chakrabarty, MD, MSPH, and Roger Zoorob, MD, MPH, from Meharry Medical College in Nashville, Tennessee. "It is a multisystem disease characterized by sleep disturbance, fatigue, headache, morning stiffness, paresthesias, and anxiety. Nearly 2 percent of the general population in the United States suffers from fibromyalgia, with females of middle age being at increased risk."
Criteria for diagnosis of fibromyalgia are those issued by the American College of Rheumatology (ACR) in 1990. These include widespread pain with a minimum duration of 3 months and the presence of 11 or more tender points at 18 specific anatomic sites.
Conditions that should be considered in the differential diagnosis of fibromyalgia include myofascial pain syndrome, chronic fatigue syndrome, and hypothyroidism. Furthermore, these conditions may also be present in patients with fibromyalgia, which renders the diagnosis more difficult.
In recent years, recognition, understanding, and diagnosis of fibromyalgia have improved. Despite the absence of well-established treatment recommendations, the authors suggest that a multidimensional approach can be effective.
Specific treatment recommendations are as follows:
Suggested treatment modalities include patient education, cognitive behavior therapy, exercise, physical therapy, and pharmacotherapy (level of recommendation, A, based on 5 randomized controlled trials).
Antidepressant medications may alleviate pain and improve sleep quality and global well-being in patients with fibromyalgia (level of recommendation, B, based on few randomized controlled trials).
Cyclobenzaprine, 10 to 30 mg at bedtime, may decrease pain and improve sleep quality in patients with fibromyalgia (level of recommendation, A, based on systematic review of randomized controlled trials).
Aerobic exercise training may ameliorate fibromyalgia symptoms (level of recommendation, A, based on systematic review of randomized controlled trials).
Fibromyalgia treatments for which there is strong evidence of effectiveness include amitriptyline, 25 to 50 mg at bedtime; cyclobenzaprine, 10 to 30 mg at bedtime; cardiovascular aerobic conditioning exercise; cognitive behavioral therapy; multidisciplinary therapy as discussed earlier; and patient education, which may take place in a group format using lectures, written materials, and demonstrations.
Fibromyalgia treatments for which there is moderate evidence of effectiveness include the dual-reuptake inhibitors duloxetine, venlafaxine, and fluoxetine, at doses of 20 to 80 mg at bedtime, either alone or in combination with a tricyclic antidepressant. Other pharmacotherapies backed by moderate evidence of effectiveness include pregabalin and tramadol, 200 to 300 mg daily, either alone or in combination with acetaminophen.
Nonpharmacologic therapies with moderate evidence of effectiveness in fibromyalgia are acupuncture, balneotherapy, biofeedback, hypnotherapy, and strength training.
Evidence to support the use of chiropractic therapy, electrotherapy, manual and massage therapy, or ultrasonography in patients with fibromyalgia is weak. Evidence to justify the use of corticosteroids, melatonin, nonsteroidal anti-inflammatory drugs, opioids, thyroid hormone, flexibility exercises, and injections of tender or trigger points is altogether lacking.
"The effectiveness of acupuncture and biofeedback has been supported by some studies," the authors conclude. "Serum levels of substance P and serotonin were significantly elevated after acupuncture treatment, suggesting possible mechanisms in pain relief. Although their effectiveness has not been proven by controlled trials, other treatment modalities employed include chiropractic therapy, yoga, tai chi, massage therapy, magnetic therapy, and tender-point injections."
The authors have disclosed no relevant financial relationships.
In an accompanying editorial, Christine N. Huynh, MD, from Virginia Commonwealth University School of Medicine in Richmond, and colleagues note that clinicians have often felt frustrated when faced with a patient with fibromyalgia because of the dearth of evidence and consensus.
However, this review, an earlier systematic review in 2004 of treatment options, and the 2005 consensus guidelines from the American Pain Society assist in the definition and management of fibromyalgia. The 1990 ACR diagnostic criteria are also clinically useful, with the caveat that fibromyalgia can be diagnosed even if the ACR's tender point criteria are not met, provided the history is highly suggestive.
"Now that there is an evidence- and consensus-based practical approach to the diagnosis and management of fibromyalgia, a higher quality of care can be provided to patients with this syndrome," Dr. Huynh and colleagues write. "Screening for disorders that may initiate or exacerbate symptoms of fibromyalgia is critical. If comorbid disorders are not identified early and treated appropriately, therapies that target fibromyalgia only as a primary disorder may be ineffective."
The editorial also highlights the controversy regarding the usefulness of opioids in fibromyalgia management, as well as the paucity of evidence supporting their use and the potential for opioid-induced hyperalgesia.
"As with any chronic pain syndrome, patients should be carefully selected for opioid therapy, and a plan should be in place for appropriate follow-up and monitoring for pain reduction, outcome improvement, side effects, and misuse," Dr. Huynh and colleagues conclude. "Physician awareness of effective nonpharmacologic and pharmacologic therapies can minimize ineffective prescribing and patient frustration associated with failure of therapy. As growing evidence from well-designed studies becomes available, physicians can confidently employ a practical and evidence-based approach to this once ill-defined syndrome."
Am Fam Physician. 2007;76:247-254.

First Treatment Approved for Fibromyalgia

June 22, 2007 — The US Food and Drug Administration (FDA) announced the approval yesterday of pregabalin (Lyrica, Pfizer) as a treatment for fibromyalgia. The drug is the first one to be approved for the treatment of this painful condition, and it has been shown to reduce pain and improve daily function for some patients.
"Today's new approval marks an important advance, and provides a reason for optimism for the many patients who will receive pain relief" with this drug, Steven Galson, MD, PhD, director of the FDA's Center for Drug Evaluation and Research in a statement. "However, consumers should understand that some patients did not experience benefit in clinical trials. We still have more progress to make for treatment of this disorder."
Pregabalin is already approved for the treatment of partial seizures, pain following rash of shingles, and pain associated with diabetic neuropathy.
Fibromyalgia is estimated to affect up to 6 million people in the United States each year. It affects mostly women and typically develops in early to middle adulthood.
Approval of pregabalin for this indication was based on 2 randomized, controlled, double-blind studies presented at the recent American Academy of Neurology and American Psychiatric Association meetings. These results, in more than 1800 patients, "support approval for use in treating fibromyalgia with doses of 300 mg to 450 mg per day," the FDA statement notes.
The most common adverse effects in these studies were mild to moderate dizziness and sleepiness, the statement adds. Blurred vision, weight gain, dry mouth, and swelling in hands and feet were also reported in the clinical trials. Adverse effects appeared to be dose-related.
"Lyrica can impair motor function and cause problems with concentration and attention," the FDA statement pointed out. "FDA advises that patients talk to their doctor or other healthcare professional about whether use of Lyrica may impair their ability to drive."
Pfizer has agreed to conduct studies of pregabalin in children with fibromyalgia and in breast-feeding women, the FDA adds.
"This is an important day for people with fibromyalgia and a real opportunity to help physicians effectively manage this disorder," said Don Goldenberg, MD, cochair of the American Pain Society's fibromyalgia guideline panel and professor of medicine at Tufts University in Boston, Massachusetts, in a statement issued by Pfizer. "Having a medication approved for use in fibromyalgia, along with research advances, will go a long way to improving our understanding and treatment of this common disorder."

FDA OKs first fibromyalgia treatment

A Pfizer Inc. drug won expanded federal approval Thursday as the first treatment for fibromyalgia, a mysterious syndrome marked by muscle pain and fatigue.
The Food and Drug Administration action means Lyrica becomes the first drug that can be marketed specifically as a treatment for adults with fibromyalgia. Patients currently make so-called "off label" use of pain medications, antidepressants, muscle relaxants and sleep aids to treat the condition. Exercise and applying heat also can help.
Fibromyalgia typically affects women, striking them with long-lasting or chronic pain, as well as muscle stiffness and tenderness, according to the FDA. An estimated 3 million to 6 million people in the United States are affected each year.
Lyrica, known generically as pregabalin, previously won FDA approval to treat partial seizures, pain following the rash of shingles and pain associated with diabetes nerve damage.
The FDA warned that common side effects of the drug included mild-to-moderate dizziness and sleepiness. Also, the agency said that Lyrica reduces pain and improves daily functions for some patients with fibromyalgia, but that not everyone derived benefit from the drug in studies.
The cause of fibromyalgia is a mystery, though it may be linked to injury, emotional distress or viruses that change the way the brain perceives pain, the FDA said.
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On the Net:
FDA information on fibromyalgia: http://www.fda.gov/consumer/updates/fibromyalgia062107.html

Gabapentin (Neurontin) Eases Chronic Pain in Fibromyalgia

CINCINNATI, June 13 -- For treating the chronic pain and other symptoms of fibromyalgia, the anticonvulsant gabapentin (Neurontin) proved safe and effective, researchers here reported.
In a 12-week randomized, double-blind clinical trial, patients taking gabapentin displayed significantly less pain, better sleep, and less fatigue than placebo controls, Lesley M. Arnold, M.D., of the University of Cincinnati, and colleagues reported in the April issue of Arthritis and Rheumatism.
However, the drug had no effect on acute pain points or depression, the researchers reported.
Although gabapentin, which was used off-label for fibromyalgia, has little, if any, effect on acute pain, it has shown a robust effect on pain caused by a heightened response to stimuli related to inflammation or nerve injury in animal models of chronic pain syndromes, Dr. Arnold said.
Studies have also found the drug to have a substantial analgesic effects on diabetic neuropathy, postherpetic neuralgia, migraine, and other neuropathic pain conditions, as well as beneficial effects on sleep and restless legs syndrome. On the basis of these findings, the researchers suspected that gabapentin might also ease fibromyalgia pain.
The study, supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, included 150 mainly white fibromyalgia patients (90% women). Of these, 75 took gabapentin at dosages of 1,200 to 2,400 mg daily for 12 weeks, while there were 75 placebo controls.
The study was conducted at three outpatient research centers in the U.S., from September 2003 to January 2006.
The mean pain severity scores, measured by the Brief Pain Inventory (BPI), decreased in both groups but more so among the gabapentin patients (P = 0.015). The estimated difference between groups at week 12 was - 0.92 (95% confidence interval -1.75, -0.71).
Of the gabapentin-treated patients, 51% achieved a response at the endpoint compared with 31% of the placebo patients (P= 0.014).
Gabapentin compared with placebo also significantly improved the BPI average pain interference score, as well as a series of other scores. These included the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity Improvement, the Patient Global Impression of Improvement, the Medical Outcomes Study (MOS), the Sleep Problems Index, and the MOS Short Form 36 vitality score.
However, the drug had no effect on acute pressure-point pain or depression (the Montgomery Asberg Depression Rating Scale), the researchers reported.
Overall, the drug was well-tolerated. Of the 150 patients, 19 dropped out due to adverse events, with no significant difference between the treatment groups.
The gabapentin patients reported dizziness, sedation, lightheadedness, and weight gain significantly more often that did the placebo-treated patients. Notably, the researchers said, there was no significant difference in weight change in the two groups as measured in the clinic, although edema may have explained some of the patients' perceptions. Most treatment adverse events, they reported, were mild to moderate in severity.
The pathophysiology of fibromyagia is unknown, but evidence suggests that it is associated with aberrant central nervous system pain processing, the researchers said.
The drug appears to be effective in reducing abnormal hypersensitivity induced by inflammatory responses or nerve injury. Yet unlike many other pain syndromes, there is no physical evidence of inflammation or CNS damage.
One possible explanation, Dr. Arnold said, is that gabapentin's effects involve binding to a specific subunit of voltage-gated calcium channels on neurons. This binding, she said, reduces calcium flow into the nerve cell, which reduces the release of some signaling molecules involved in pain processing.
In discussing the study's limitations, the researchers said that because the study was short, the results may not generalize to longer treatment periods, and long-term efficacy should be studied in future clinical trials.
Also, because the study was relatively small, they said it may have lacked the power to detect potentially relevant differences between the groups. Finally, they wrote that the results may not apply to patients with some comorbid psychiatric disorders, such as bipolar disorder, or to patients with other painful musculoskeletal disorders.
"In this, the first randomized, placebo-controlled study to evaluate gabapentin in the treatment of fibromyalgia, the results demonstrated that gabapentin, taken for up to 12 weeks, is effective and safe in the treatment of pain and other symptoms associated with fibromyalgia," Dr. Arnold concluded. Primary source: Arthritis and RheumatismSource reference: Arnold LM, et al "Gabapentin in the Treatment of Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial" Arthritis Rheum 2007; 56: 1336-1344.