The American College of Rheumatology defines fibromyalgia syndrome (FMS) as widespread pain that must have been present for at least three months with 11 of 18 specific tender points found on digital palpation.^1,2

The signs and symptoms of fibromyalgia include diffuse muscle pain and aches, muscle stiffness, sleep disturbances, fatigue, decrease in physical activity and tenderness over discrete tender points.¹ The disease can be very debilitating due to the fatigue, diffuse pain and the overall decrease in quality of life.^1,3

The cause and pathophysiology of fibromyalgia remain unclear. There are several theories that are supported by marginal information. The role of serotonin metabolism is supported by evidence that there are lowered levels of tryptophane and serotonin in groups of patients with chronic pain syndromes including FMS.⁴ Substance P is a potent mediator of pain and seems important in triggering the pain pathway and has been found to be elevated in the cerebrospinal fluid in fibromyalgia patients.⁵

There is evidence to support the interaction between substance P and 5-hydroxytryptamine-receptors (5-HT3) in inducing pain. 5-HT3-receptor is a serotonin receptor and when stimulated causes the release of substance P, therefore, increased serotonin activity may result in generalized substance P mediated pain.²

Even with of all these theories, medical treatment of fibromyalgia is unsatisfactory.² The purpose of this article is to look at the potential therapy for fibromyalgia compared with the current standards of treatment.

Methods

In this literature review, a mixture of peer-reviewed medical and allied health journals were accessed. Original research, randomized control trials, two retrospective meta-analyses and one review article were utilized. The search was limited to articles published between 1990 and 2004.

These articles were accessed through Medline with MESH terms of fibromyalgia, treatment, tropisetron, venlafaxine, and antidepressants. The American College of Rheumatology Web site provided the criteria for the current standards of treatment.

Current Treatment

The current treatment for fibromyalgia is diversified and includes the use of medications such as NSAIDs, antidepressants and muscle relaxants to help control the pain. Other nonmedical options include exercise-based programs and cognitive behavioral therapy involving the use of learning techniques. Cognitive behavioral therapy uses both individual and group interventions designed to improve the patient's internal control of reactivity in situations of chronic pain.

Cyclobenzaprine is the muscle relaxant Flexeril that modulates muscle tension at a supraspinal level and is used in up to 12% of patients diagnosed with fibromyalgia.⁶ A meta-analysis showed that patients are about three times as likely to report improvement in symptoms compared with placebo.⁶ That is, one in five people would improve with treatment. Participants reported no significant improvement in fatigue, tender points or pain at the end of the trial, proving that the overall efficacy of cyclobenzaprine as a monotherapy is only partially effective in treating FMS.⁶

The antidepressant class is one of the most prescribed medications for FMS. The role of psychological factors in the pathogenesis of fibromyalgia is controversial. Depression is common with fibromyalgia, but it has not been determined whether depression is a primary cause of fibromyalgia or whether it is a reaction to the debilitating symptoms of the disease. A meta-analysis of the antidepressant class showed mild benefit on trigger points and fatigue, and moderate improvement for sleep, overall well-being and pain severity.⁷ That means that patients treated with antidepressants were more than four times as likely to improve or that one in four people treated with antidepressants will improve.⁷

Although the results of the meta-analysis were encouraging the majority of the studies examined involved amitriptyline, a tricyclic antidepressant. When examining solely the SSRI class, studies have had mixed results as to the effectiveness of treatment in FMS. Norregaard and colleagues and Wolfe and colleagues produced similar results when studying SSRIs.^8,9 Both showed no improvement between control group and the treatment group in their trials.

Anderberg and colleagues showed at the end of a four-month trial, there was marginal improvement in the SSRI treatment group compared with placebo group in the global judgment of pain and global judgment of well-being but neither were of statistical significance.¹⁰ The only factor to have a proven statistical difference was sleep.

Arnold and colleagues studied fluoxetine in a randomized, placebo-controlled, double-blind trial. The results of the study showed that the group treated with fluoxetine significantly improved compared with the placebo group. This improvement was noticed in the Fibromyalgia Impact Questionnaire (FIQ) total score and the FIQ measurements of pain, fatigue and depression. Tender points and myalgic scores did not significantly improve after treatment.¹¹ The overall results of these trials prove that SSRIs fail to relieve all the symptoms of FMS.

The effectiveness of amitriptyline and fluoxetine have been determined to be somewhat beneficial as monotherapy in treating fibromyalgia, a trial by Goldenberg and colleagues examined their efficacy when taken together. The results showed that when used in combination, amitriptyline and fluoxetine produced significantly better results than either drug alone, based upon the FIQ and the Visual Analog Scales (VAS) for pain, global well-being and sleep. The tender point score did not change significantly despite improvement in the pain, global well-being and functional score.¹²

NSAIDs as a class have shown little evidence that they are effective when used alone in FMS. Tramadol though has had the best results with three randomized control trials showing improvement in patients' VAS scores, improved pain relief and decreased pain threshold after treatment.13-15 NSAIDs still are only recommended as adjunct therapy and are not considered first-line agents.¹³

Physical Exercise and Cognitive Behavioral

Other available options for treatment of FMS include physical exercise and the cognitive behavioral approach to treatment. In a study consisting of a multidisciplinary program with group interventions including warm water swimming, relaxation exercises, low-impact land exercises, learning activities of daily living and education-discussion sessions, significant results were acquired. The treatment group showed a significant improvement in Psychological General Well Being index for anxiety, vitality and total score. They also had significant improvements in the FIQ for fatigue, morning stiffness, anxiety and total score. But no significant effect on pain severity was demonstrated.³

Redondo and colleagues and Richards and colleagues examined physical exercise compared with either relaxation techniques with stretching or cognitive behavioral therapy. Overall the physical exercise group had better long term efficacy compared to the cognitive behavioral group or the relaxation/flexibility group.^16,17