Methods: 888 patients were randomized to placebo (n=223), milnacipran 100 (n=224), or 200 mg/day (n=441) for 6 months. The study protocol was approved by each center's IRB; patients gave written, informed consent. Pain responders were defined as patients having a ≥30% improvement from baseline in pain (patient experience diary, PED) and global improvement (a rating of “very much improved” or “much improved” on the Patient Global Impression of Change, PGIC). “Syndrome responders” were based on the above criteria plus ≥6 point improvement on SF-36 PCS score.

Results: The pain composite responder for milnacipran 200 mg/day was significantly improved over placebo (3 months, P=.032; 6 months, P=.034). Milnacipran demonstrated significant improvement over placebo for the syndrome composite responder at 3 months (100 mg/day, P=.028; 200 mg/day, P=.017). Pre-specified secondary analyses revealed that milnacipran 200 mg/day led to significant improvements on multiple domains at 3 months: PED morning recall pain (P=.010), real-time pain (P=.010), weekly recall pain (P=.018), PGIC (P ≤.001), Multidimensional Fatigue Inventory (MFI) total score (P=.016), and Multiple Ability Self-Report Questionnaire (MASQ, cognition total score, P=.025), as well as improvements in multiple SF-36 domains. A significant reduction in pain was observed after 1 week. In patients completing the trial, composite pain response rates were: 27.9%, placebo; 43.8%, 100 mg/day (P=.012); and 45.2%, 200 mg/day (P<.001). In the drug-treated groups, the most common side effects were nausea, headache, and constipation.

Conclusions: These data suggest that milnacipran is safe and effective in treating pain and the multidimensional symptoms associated with fibromyalgia.