A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia.
OBJECTIVE
This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.


METHODS
Outpatients diagnosed with FM according to 1990 American College of Rheumatology criteria (N = 884) were randomized to placebo (n = 449) or milnacipran 200 mg/day (n = 435) for 17 weeks (4-week dose escalation, 12-week stable dose, 9-day down-titration), followed by a 2-week posttreatment period. The primary efficacy criterion was a 2-measure composite responder analysis requiring patients to achieve simultaneous improvements in pain (>or= 30% improvement from baseline in visual analog scale, 24-hour morning recall) and a rating of "very much" or "much" improved on the Patient Global Impression of Change scale. If responder analysis was positive, Fibromyalgia Impact Questionnaire (FIQ) was included as an additional key primary efficacy measure.


RESULTS
At the end of the stable dose period (Week 16), milnacipran 200 mg/day showed significant improvements from baseline relative to placebo in the 2-measure composite responder criteria (p = 0.0003) and FIQ total score (p = 0.015). Significant improvements were also observed in multiple secondary efficacy endpoints, including Short-Form 36 Health Survey (SF-36) Physical Component Summary (p = 0.025), SF-36 Mental Component Summary (p = 0.007), Multidimensional Fatigue Inventory (p = 0.006), and Multiple Ability Self-Report Questionnaire (p = 0.041). Milnacipran was safe and well tolerated; nausea, hyperhidrosis, and headache were the most common adverse events.


CONCLUSIONS
Milnacipran is an effective and safe treatment for pain and other predominant symptoms of FM. Registered as trial no. NCT00436033.
Branco
Jaime C
JC
Faculdade Ciências Médicas, Universidade Nova de Lisboa, Serviço de Reumatologia, CHLO, EPE-Hospital Egas Moniz, Lisboa, Portugal.
Zachrisson
Olof
O
Perrot
Serge
S
Mainguy
Yves
Y
D000328:Adult; D000368:Aged; D003521:Cyclopropanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017060:Patient Satisfaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors