Introduction

The term fibromyalgia is applied to the syndrome that, as its name implies, consists of chronic widespread muscular pain and stiffness, which is associated with several discrete tender points, as well as generalized symptoms like fatigue or insomnia. Over 3.5 million people in the USA are afflicted, according to the diagnostic criteria established by a committee formed by the American College of Rheumatology in 1990.¹ Women aged between 35 and 60 account for 75% of the patients. Sufferers may have associated symptoms - the irritable bowel syndrome, Raynaud syndrome, headache, paresthesia, distress and functional disability.

Pathophysiology

The cause of the fibromyalgia is unknown, although various physiological changes have been found in patients:

• A nonrestorative sleep pattern - alpha-wave non-REM sleep occurs with increased frequency
• Structural and functional muscle abnormalities (e.g. "moth-eaten" and "ragged-red" muscle fibers, local hypoxia) - the constancy of these changes is, however, disputed
• Impaired neuroendocrine (hypothalamic-pituitary-adrenal axis) functioning - again, the relevance of these findings is unclear
• Decreased serum serotonin levels, increased substance P and decreased nor-epinephrine in the cerebrospinal fluid - not a consistent finding, however.
• Decreased regional cerebral blood flow (thalamus and caudate nucleus) reported in a few patients needs to be confirmed in a larger sample.

Theoretically, a neurotransmitter abnormality, involving perhaps insulin-like growth factor-1, could be responsible. Impaired muscle metabolism or blood flow seems unlikely.

Treatment - Pharmacological

Fewer than 50% of patients will experience adequate relief - indeed one study reported that only 3% of patients at a 3-year follow-up had remission of all pain symptoms. The main drug classes studied include: tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), benzodiazepines, analgesics, anti-inflammatory agents, lidocaine, and opioids.

• Tricyclic antidepressants, such as amitriptyline, can alleviate symptoms, though only 25% to 30% of patients achieve clinically significant improvements. Side effects and tachyphylaxis further limit their usefulness.
• SSRIs have produced positive results, but reduction of tender-point pain and overall pain relief is inconsistent. They are probably best combined with a tricyclic antidepressant at bedtime.
• Benzodiazepines, used alone, have not yielded convincing results in fibromyalgia, and their long-term use carries the risk of dependence and withdrawal seizures.
• The analgesic tramadol - a synthetic codeine analog - has been shown to be useful in treating the pain of fibromyalgia - it was as effective as a combination of acetaminophen with codeine.
• Non-steroid anti-inflammatory drugs and corticosteroids have not proved efficacious in fibromyalgia.
• Lidocaine, given as multiple injections at tender points, offers some relief, but "dry-needling" (which also increases met-enkephalin levels at the site) has similar benefits.
• Opioids remain a final option; their efficacy in fibromyalgia remains uncertain, and their potential for harm (side effects, dependency, tolerance and toxicity) is considerable.

Recently the naturally occurring derivative of methionine, S-adenosyl-L-methionine (SAMe) has been used with apparent success in treating fibromyalgia, using both oral and intramuscular forms. The lack of an inflammatory component in fibromyalgia suggests that the benefits of SAMe are related to its somewhat controversial antidepressant or analgesic actions. Other drugs that have been tried, with varying success, include 5-hydroxytryptophan, calcitonin, ondansetron, growth hormone, and gamma-hydroxybutyrate. The relative lack of effectiveness of pharmacological treatments in general has led, not surprisingly, to the use of non-pharmacological methods.

Treatment - Non-pharmacological

Exercise - aerobic exercise three times a week - can reduce tender-point pain and overall pain, although sleep and fatigue may be unresponsive.

Biofeedback, using electromyographic activity, has similar benefits to aerobic exercise, and combination of these two approaches has proved particularly beneficial.

Hypnotherapy was shown in a controlled study to provide more benefit than physical therapy in refractory fibromyalgia, but the study may have shown selection bias - it employed patients already refractory to physical therapy.

Acupuncture has been applied with success in treating general pain, but little work has been reported in fibromyalgia patients. However, the condition is included in a list of situations where acupuncture "may be useful" issued by the National Institutes of Health.

Cognitive-Behavioral Treatment

Combinations of relaxation training, meditation, cognitive restructuring, aerobic exercise and stretching, activity pacing, and patient/family education, together with prescribed drug treatment, produced improvement in most symptoms of fibromyalgia over a 24-week period. However, similar benefits were seen in patients given a less-intensive regimen concentrating on relaxation, and in those treated in group therapy. The author of this review believes integrated behavioral therapy shows most promise for patients with recent-onset fibromyalgia.

Comment

Fibromyalgia is a chronic painful condition without obvious cause or cure. These features make it an obvious candidate for allocation to the collective of functional somatic syndromes. Nevertheless, the symptoms and tender points are most distressing, and demand treatment. Among the pharmacological approaches that provide measurable relief, oral tramadol, injection of tender points with lidocaine, and the judicious use of antidepressants (tricyclics and SSRIs) can be recommended. Non-pharmacological interventions (behavioral modification, exercises, relaxation training, acupuncture and hypnotherapy) have also provided relief. It seems probable that a multidisciplinary approach, using a combination of pharmacological and non-pharmacological treatments in a trial-and-error manner, offers the only hope for patients until a major breakthrough occurs in our understanding of this condition.