Gendreau R Michael, Thorn Michael D, Gendreau Judy F, Kranzler Jay D, Ribeiro Saulo, Gracely Richard H, Williams David A, Mease Philip J, McLean Samuel A, Clauw Daniel J
Cypress Biosciences, 4350 Executive Drive, San Diego, CA 92121, USA.
J Rheumatol. 2005 Oct;32(10):1975-85.
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.
纤维肌痛（FM）是一种常见的肌肉骨骼疾病，其特征为广泛疼痛、压痛及多种其他躯体症状。目前的治疗效果一般。可以说，研究最充分且最有效的化合物是三环类抗抑郁药（TCA）。米那普明是一种非三环类化合物，可抑制5-羟色胺和去甲肾上腺素的再摄取，可能具有TCA的许多有益作用，且副作用较小。
在一项双盲剂量递增试验中，125例FM患者按3:3:2的比例随机分组，分别接受每日两次米那普明、每日一次米那普明或安慰剂治疗3个月；每日两次用药的参与者中有92%、每日一次用药的参与者中有81%的剂量递增至米那普明目标剂量200mg。
主要终点是疼痛减轻。每日一次和每日两次用药组在疼痛方面均有统计学意义的显著改善，在整体健康、疲劳及其他方面也有改善。接受米那普明治疗的患者，无论有无合并抑郁症，其缓解率相同，但安慰剂在抑郁症患者中的缓解率明显更高，导致非抑郁症组的总体疗效显著更高。
在这项II期研究中，米那普明使FM的疼痛和其他症状有统计学意义的显著改善。效应大小与先前使用TCA时发现的相同，且该药物总体耐受性良好。
