Efficacy of milnacipran in patients with fibromyalgia.

Cypress Biosciences, 4350 Executive Drive, San Diego, CA 92121, USA.
The Journal of Rheumatology (Impact Factor: 3.17). 11/2005; 32(10):1975-85.
Source: PubMed

ABSTRACT Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA). Milnacipran, a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine, may provide many of the beneficial effects of TCA with a superior side effect profile.
One hundred twenty-five patients with FM were randomly assigned in a 3:3:2 ratio to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months in a double-blind dose-escalation trial; 92% of twice-daily and 81% of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg.
The primary endpoint was reduction of pain. Both the once- and twice-daily groups showed statistically significant improvements in pain, as well as improvements in global well being, fatigue, and other domains. Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression, but placebo response rates were considerably higher in depressed patients, leading to significantly greater overall efficacy in the nondepressed group.
In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated.

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    ABSTRACT: Antidepressant drugs are commonly used to treat fibromyalgia but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled, clinical trial with milnacipran; a noradrenalin-serotonin re-uptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus-response assessments of pressure-pain, measures of weekly pain and fibromyalgia impact. Following treatment, milnacipran-responders exhibited significantly higher activity in the posterior cingulum, compared to placebo-responders. The mere exposure to milnacipran did not explain our findings since milnacipran-responders exhibited increased activity also in comparison to milnacipran non-responders. Stimulus-response assessments revealed specific antihyperalgesic effects in milnacipran-responders, which also correlated to reduced clinical pain and to increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing; an alteration implicated in fibromyalgia pathophysiology. Perspective The present article presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo- and milnacipran-responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain.
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