Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized,double‐blind,placebo‐controlled trial

Objective

To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.

Methods

A double‐blind, placebo‐controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4–6 weeks of flexible dose escalation followed by 12 weeks of stable‐dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2‐measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of “very much improved” or “much improved” on the Patient's Global Impression of Change (PGIC) scale. The 3‐measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF‐36) physical component summary (PCS) score.

Results

After 12 weeks of stable‐dose treatment, a significantly greater proportion of milnacipran‐treated patients compared with placebo‐treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2‐measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3‐measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran‐treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24‐hour and weekly recall pain score, PGIC score, SF‐36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo‐adjusted rate of 15.8%).

Conclusion

Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.