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

Abstract

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.

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

“…Milnacipran is an SNRI that has antinociceptive effects in the musculoskeletal pain condition, fibromyalgia (Arnold et al, 2010), and models of inflammatory and neuropathic pain (Iyengar et al, 2004;King et al, 2006;Mico et al, 2011). This is the first published study examining whether milnacipran also has antinociceptive effects in a model of OA, and demonstrates that this antidepressant reduces the mechanical hypersensitivity that presents at the hind-paw in both the early and late phases of the MIA model.…”

Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia

“…We included eight new studies (nine reports) (Arnold 2012a; Bateman 2013; Clauw 2013; Leombruni 2015; Matthey 2013; Murakami 2015; NCT00697787; Staud 2015). …”

Effects of Milnacipran on the Multidimensional Aspects of Fatigue and the Relationship of Fatigue to Pain and Function

“…In study 1 (n = 888) 40 and study 2 (n = 1196), 41 eligible patients were randomized to receive milnacipran 100 mg/d, 200 mg/d, or placebo. Patients in study 3 (n = 1025) 42 received milnacipran 100 mg/d or placebo. The analyses presented in this report are based on the 3-month data collected from the 3109 patients in all of these studies.…”