Pharmacotherapy of Fibromyalgia
Pharmacotherapy of Fibromyalgia
Purpose. Published evidence on the pathophysiology, diagnosis, and treatment of fibromyalgia is reviewed, with an emphasis on recent clinical trials of various pharmacologic agents.
Summary. Fibromyalgia affects an estimated 2% of the general U.S. population, and its incidence is sevenfold higher among women. The diagnostic characteristics of fibromyalgia are chronic widespread pain, thought to arise from abnormalities of ascending pain and descending inhibitory sensory pathways, and allodynia on palpation of specific tender points. Three medications available in the United States are labeled for treatment of fibromyalgia-related symptoms: the serotonin- and norepinephrine-reuptake inhibitors duloxetine and milnacipran and the α2-δ ligand pregabalin. Evidence from clinical trials indicates that all three drugs can have a significant impact on fibromyalgia-related pain; duloxetine and pregabalin have been demonstrated to reduce sleep disturbances and improve quality of life (the former also has been shown to improve mood), while milnacipran can offer significant benefits in reducing fatigue. A growing body of evidence suggests that the best treatment approach may involve the use of one or more agents whose mechanisms of action are aligned with patient-specific clusters of symptoms. Several other agents have been used for fibromyalgia, with mixed results, including tricyclic antidepressants, selective serotonin-reuptake inhibitors, opioids, and gabapentin. Given the limitations of the evidence from clinical trials to date, controlled trials directly comparing different agents are needed to better delineate adverse-event risks, cost considerations, and optimal management approaches.
Conclusion. A broad range of drugs has been used to treat fibromyalgia. Symptoms, comorbidities, adverse effects, and patient preference are important considerations in drug selection.
Syndromes consistent with what is now termed fibromyalgia have been described in the medical literature for centuries. In 1763, a French physician described a condition called "muscular rheumatism" with symptoms including "'pain in the fleshy parts' without fever." In 1904, the term fibrositis came into use because the symptoms were thought to be caused by inflammation of the fibrous tissue over the muscles.
In the 1970s, the contemporary concept of fibrositis (i.e., a disorder characterized by sleep disturbance and tender points) was developed. Over the next 20 years, as antiinflammatory medications were found to give incomplete relief of pain and other symptoms in patients with fibrositis, and as muscle biopsies in such patients found no inflammation, the term fibrositis became incongruent with knowledge and understanding of the disease. In 1990, the American College of Rheumatology (ACR) issued classification criteria recommending the use of the term fibromyalgia instead of fibrositis to describe the condition. Since then, our understanding of pain syndromes and fibromyalgia has continued to progress. Some researchers and clinicians now believe that fibromyalgia is part of a larger continuum of "central sensitivity syndromes."
Abstract and Introduction
Abstract
Purpose. Published evidence on the pathophysiology, diagnosis, and treatment of fibromyalgia is reviewed, with an emphasis on recent clinical trials of various pharmacologic agents.
Summary. Fibromyalgia affects an estimated 2% of the general U.S. population, and its incidence is sevenfold higher among women. The diagnostic characteristics of fibromyalgia are chronic widespread pain, thought to arise from abnormalities of ascending pain and descending inhibitory sensory pathways, and allodynia on palpation of specific tender points. Three medications available in the United States are labeled for treatment of fibromyalgia-related symptoms: the serotonin- and norepinephrine-reuptake inhibitors duloxetine and milnacipran and the α2-δ ligand pregabalin. Evidence from clinical trials indicates that all three drugs can have a significant impact on fibromyalgia-related pain; duloxetine and pregabalin have been demonstrated to reduce sleep disturbances and improve quality of life (the former also has been shown to improve mood), while milnacipran can offer significant benefits in reducing fatigue. A growing body of evidence suggests that the best treatment approach may involve the use of one or more agents whose mechanisms of action are aligned with patient-specific clusters of symptoms. Several other agents have been used for fibromyalgia, with mixed results, including tricyclic antidepressants, selective serotonin-reuptake inhibitors, opioids, and gabapentin. Given the limitations of the evidence from clinical trials to date, controlled trials directly comparing different agents are needed to better delineate adverse-event risks, cost considerations, and optimal management approaches.
Conclusion. A broad range of drugs has been used to treat fibromyalgia. Symptoms, comorbidities, adverse effects, and patient preference are important considerations in drug selection.
Introduction
Syndromes consistent with what is now termed fibromyalgia have been described in the medical literature for centuries. In 1763, a French physician described a condition called "muscular rheumatism" with symptoms including "'pain in the fleshy parts' without fever." In 1904, the term fibrositis came into use because the symptoms were thought to be caused by inflammation of the fibrous tissue over the muscles.
In the 1970s, the contemporary concept of fibrositis (i.e., a disorder characterized by sleep disturbance and tender points) was developed. Over the next 20 years, as antiinflammatory medications were found to give incomplete relief of pain and other symptoms in patients with fibrositis, and as muscle biopsies in such patients found no inflammation, the term fibrositis became incongruent with knowledge and understanding of the disease. In 1990, the American College of Rheumatology (ACR) issued classification criteria recommending the use of the term fibromyalgia instead of fibrositis to describe the condition. Since then, our understanding of pain syndromes and fibromyalgia has continued to progress. Some researchers and clinicians now believe that fibromyalgia is part of a larger continuum of "central sensitivity syndromes."
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