Methods: 1196 patients were randomized to placebo (n=401), milnacipran 100 (n=399) or 200 mg/day (n=396) for 15 weeks. The primary outcome measure was a composite responder analysis of multiple domains: pain (patient experience diary, PED) global improvement (Patient Global Impression of Change, PGIC) and physical function (SF-36 PCS). "Pain responders" were defined as patients having a ≥30% improvement from baseline in pain and a rating of "very much improved" or "much improved" on the PGIC. "Syndrome responders" were based on the above criteria plus improvement in physical function ≥6 point improvement on SF-36 PCS score. The study protocol was approved by each center's Institutional Review Board; patients gave written, informed consent.

Results: At 15 weeks, compared to placebo, milnacipran resulted in a significant increase in composite responder rates for pain (100 mg/day, P=.025; 200 mg/day, P=.004) and for syndrome (100 mg/day, P=.011; 200 mg/day, P=.015). Milnacipran significantly improved pain within 1 week of dosing. Both doses of milnacipran led to significant improvements in secondary efficacy assessments: pain scores (P<.001); PGIC (P<.001); SF-36 MCS (P<.05, 200 mg/day) as well as improvement in SF-36 PCS scores. Milnacipran was associated with significant improvements in Fibromyalgia Impact Questionnaire (FIQ) and Multidimensional Fatigue Inventory (MFI). Discontinuation rates were similar between groups. Most common AEs were nausea and headache. AEs occurring at ≥5% and twice placebo were constipation, hyperhidrosis, hot flashes, dizziness, vomiting, increased heart rate, migraine, palpitations, and hypertension.

Conclusions: These findings confirm that milnacipran is safe and well tolerated and is an effective treatment for the multidimensional symptoms of fibromyalgia syndrome, including pain.