The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To evaluate the safety and efficacy of milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM).


METHODS
A 27-week, randomized, double-blind, multicenter study compared milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. Two composite responder definitions were used to classify each patient's individual response to therapy. "FM responders" concurrently satisfied response criteria for improvements in pain (visual analog scale 24-h morning recall), patient global impression of change (PGIC), and physical functioning (SF-36 Physical Component Summary); while "FM pain responders" concurrently satisfied response criteria for improvements in pain and PGIC.


RESULTS
At the primary endpoint, after 3-month stable dose treatment, a significantly higher percentage of milnacipran-treated patients met criteria as FM responders versus placebo (milnacipran 200 mg/day, p = 0.017; milnacipran 100 mg/day, p = 0.028). A significantly higher percentage of patients treated with milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032). Significant pain reductions were observed after Week 1 with both milnacipran doses. At 15 weeks, milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and weekly recall; all measures, p < 0.05), PGIC (p < 0.001), fatigue (p = 0.016), cognition (p = 0.025), and multiple SF-36 domains. Milnacipran was safe and well tolerated by the majority of patients during 27 weeks of treatment; nausea and headache were the most common adverse events.


CONCLUSIONS
Milnacipran is safe and effective for the treatment of multiple symptoms of FM.
Mease
Philip J
PJ
Seattle Rheumatology Associates, 1101 Madison Street, Suite 1000, Seattle, WA 98104, USA. pmease@philipmease.com
Clauw
Daniel J
DJ
Gendreau
R Michael
RM
Rao
Srinivas G
SG
Kranzler
Jay
J
Chen
Wei
W
Palmer
Robert H
RH
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology; D003521:Cyclopropanes / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy* / Q000503:physiopathology; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D009325:Nausea / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D003521:Cyclopropanes; D000078764:Milnacipran; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors