Of the three SNRIs, duloxetine has the most randomized trial data to support its use in the treatment of fibro-myalgia. Among fibromyalgia patients with or without major depressive disorder, duloxetine improved pain and functioning independent of depression.91,92[II] The clinical improvements were evident in patients randomized to receive either duloxetine 60mg/day or 60 mg twice daily Using a similar study design, fibromyalgia patients with and without depression were randomized to receive mil-nacipran once (mean dose, 174 mg) or twice (mean dose, 191 mg) daily.93[II] At study completion, both treatment groups experienced significant improvements in pain and global well-being, but patients in the higher-dose group experienced improvements in physical functioning. The less favorable outcomes of the once-daily dosage group could have been due in part to the short half-life of the drug. Randomized trial data are not available for venlafaxine in the treatment of fibromyalgia, but two prospective open-label trials found significant improvements in both pain and physical functioning.94, 95[III]

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