Pain arthritis neuropathy fibromyalgia
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
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Chronic pain may occur as the end result of many problems including joint damage (arthritis) or nerve damage (neuropathy).
Fibromyalgia does not cause joint damage and it is not associated with nerve damage.Nonetheless, it causes significant pain that may be misdiagnosed as being either joint or nerve related. There is some data that fibromyalgia may be due to central nervous system neurotransmitter dysfunction.
Clinicians often use older tricyclic antidepressants to treat chronic pain syndromes such as fibromyalgia or diabetic neuropathy. These medications are moderately effective in treating these conditions but can cause serious side effects.
The selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are more recent class of antidepressants. They are better tolerated than are tricyclic antidepressants. Blocking the reuptake of serotonin and norepinephrine has been hypothesized to affect the pain modulating systems in the brainstem. Several studies have examined the use of SSRIs and SNRIs in pain syndromes. Most of these involved patients with fibromyalgia or diabetic neuropathy.
Fibromyalgia is a syndrome of widespread chronic musculoskeletal pain with increased tenderness at specific anatomic sites. There have been case reports of patients with fibromyalgia who have responded to fluoxetine therapy. These reports prompted several randomized controlled trials. The first, by Wolfe et al, compared 20 mg/d of fluoxetine to placebo in 42 women during a 6-week period. There was no difference between the fluoxetine and placebo groups in pain scores, or global severity of disease. Unfortunately 28% of the active treatment and 57% of the placebo patients withdrew from the study before its completion. The low number of patients severely limited the power of this study to detect meaningful improvements due to fluoxetine therapy. In a more recent study Goldenberg et al compared fluoxetine, 20 mg/d, and amitriptyline, 25 mg/d, with placebo in a randomized, double-blind, crossover study. Nineteen patients were randomized in a crossover fashion to fluoxetine vs placebo, fluoxetine and amitriptyline vs placebo or amitriptyline vs placebo. Individually, patients receiving both fluoxetine and amitriptyline had improvement in pain compared with placebo, global well-being, and sleep disturbance scores. The combination of fluoxetine and amitriptyline was more effective than either alone. Another study of SSRIs for fibromyalgia used citalopram which is not licensed in the United States. In this double-blind, placebo-controlled study in 22 patients Norregaard et al found no improvement in pain scores or global functioning.
Diabetic neuropathy is a symmetric, usually distal neuropathy, associated with diabetes mellitus. The sensory symptoms often include burning or throbbing extremity pain. A few studies have examined whether SSRIs are valuable in relieving the pain of diabetic neuropathy. In a randomized, double-blind, crossover study of 20 patients, Sindrup et al compared paroxetine, 40 mg/d, with dose adjusted imipramine, median 200 mg/d. Paroxetine reduced neuropathy pain more than placebo but less than imipramine. In a similar study, Sindrup et al also found that citalopram, a SSRI not licensed in the United States, had a small effect in relieving diabetic neuropathy pain. In the largest study of 46 patients, Max et al compared amitriptyline with desipramine and fluoxetine with placebo in a randomized, double-blind, crossover trial with each treatment period lasting 6 weeks. The dosages were titrated for each patient with mean daily dosages of: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. The end points evaluated were daily pain scores and global pain relief at the end of treatment. Fluoxetine was no better than placebo except in the subset of depressed patients. Amitriptyline and desipramine were equally effective.
There is reasonable evidence that fluoxetine, 20 mg/d, is effective in reducing pain and improving global well-being in patients with fibromyalgia. The combination of amitriptyline, 25 mg/d, and fluoxetine, 20 mg/d, may offer more benefit than either alone.
Since then there has been abundant data indicating that SNRIs such as Cymbalta and Savella, have a superior effect in treating fibromyalgia. Both are FDA approved for that condition. In addition another class of drugs, the GABA stimulators such as neurontin and Lyrica have been found to be effective as well for treating both fibromyalgia as well as neuropathic pain.
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