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%).


CONCLUSIONS
Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.
Arnold
Lesley M
LM
University of Cincinnati College of Medicine, Cincinnati, Ohio 45219, USA. lesley.arnold@uc.edu
Gendreau
R Michael
RM
Palmer
Robert H
RH
Gendreau
Judy F
JF
Wang
Yong
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D003521:Cyclopropanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D017060:Patient Satisfaction; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D003521:Cyclopropanes; D000078764:Milnacipran; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors