The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial

Mease, Philip J.; Clauw, Daniel J.; Gendreau, R. Michael; Rao, Srinivas G.; Kranzler, Jay D; Chen, Wei; Palmer, Robert H.

doi:10.3899/jrheum.080734

Cited by 240 publications

(282 citation statements)

References 52 publications

(37 reference statements)

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“…These results differ from those in previous trials, in which treatment with a higher dosage of milnacipran 200 mg/day (100 mg twice daily) led to significant improvements in cognitive function after 3 and 6 months of treatment (6,7). More studies using structured cognitive testing in addition to self-report measures are needed to assess further the cognitive function of patients with fibromyalgia and the response of cognitive symptoms to treatment.…”

Section: Discussioncontrasting

confidence: 83%

“…The results of this trial are consistent with those of 2 previous pivotal studies of milnacipran using the same composite response criteria (6,7). Use of the composite responder definition in these studies allows for an assessment of clinically meaningful improvements across multiple symptom and function domains in individual patients.…”

Section: Discussionsupporting

confidence: 81%

“…Milnacipran was tolerated by most of the patients in the present study. The proportion of milnacipran-treated patients (17.8%) compared with placebo-treated patients (13.9%) who withdrew from the study due to AEs was somewhat less than was reported in the 2 previous pivotal fibromyalgia trials of milnacipran, in which about twice as many patients in the 50 mg twice daily group withdrew from the studies due to AEs as compared with the placebo group (6,7). Although the incidences of nausea and other TEAEs in this study were generally similar to previously reported data, the overall TEAE incidence rates do not reflect severity or other factors that might contribute to discontinuation.…”

Section: Discussionmentioning

confidence: 65%

“…Recent pivotal trials of milnacipran were among the first to use composite responder definitions as primary outcome measures in large-scale studies of fibromyalgia (6,7). Two composite responder definitions were included in these trials to assess efficacy (2-measure and 3-measure composite responder definitions).…”

mentioning

confidence: 99%

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

Arnold

Gendreau

Palmer³

et al. 2010

Arthritis & Rheumatism

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127

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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.

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Section: Discussioncontrasting

confidence: 83%

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

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

Arnold

Gendreau

Palmer³

et al. 2010

Arthritis & Rheumatism

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127

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“…These studies showed that Savella (100 and 200 mg/day) demonstrated clinically significant improvements compared with placebo in treating fibromyalgia. A larger number of Savella-treated patients experienced at least a 30% reduction in pain from baseline as well meeting the criteria for a treatment response as measured by improvements in pain, physical function, and patient global assessment (4,5).…”

mentioning

confidence: 99%

ACS Chemical Neuroscience Molecule Spotlight on Savella

Hopkins

2010

ACS Chem. Neurosci.

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Savella (milnacipran), a selective serotonin and noradrenaline reuptake inhibitor, was approved by the FDA on January 14th, 2009, for the treatment of fibromyalgia.S avella (milnacipran) is a recently approved psychoactive drug from Cypress Biosciences for the treatment of fibromyalgia (1). Fibromyalgia is a complex medical disorder characterized by chronic, widespread pain and allodynia (a heightened and painful response to pressure). This disorder is present is approximately 2% of the U.S. population and is much more likely to develop in women than in men; with the risk increasing with age (2). Although many cases of fibromyalgia develop after a physical or emotional trauma, in many other instances there appears to be no triggering event. People with fibromyalgia usually also have sleep disorders that prevent the individuals from reaching the deep, restorative stages of sleep. Due to this, many people also have other coexisting conditions, such as chronic fatigue syndrome, depression, and headaches, among others. Savella (milnacipran) is an inhibitor of serotonin and norepinephrine reuptake in an approximate 3:1 ratio. In vitro, using radiolabeled serotonin and noradrenaline, milnacipran had potency against serotonin of IC 50 = 203 nM and noradrenaline IC 50 = 100 nM (3). In addition, milnacipran showed no activity for R-or β-adrenoceptors, muscarinics, histamine H 1 , dopamine D 2 , or serotonin 5-HT 2 receptors (3). These results would suggest that milnacipran would be a useful and novel antidepressant drug; and in fact, it is. Milnacipran was first approved in France for the treatment of major depressive episodes in 1996 (marketed as Ixel). It is currently marketed for depression in over 45 countries, and in 2003, Cypress Biosciences purchased the exclusive rights for any purpose in the U.S. and Canada from Pierre Fabre.The efficacy and ultimately the FDA approval were based on two pivotal clinical trials in the U.S. These studies showed that Savella (100 and 200 mg/day) demonstrated clinically significant improvements compared with placebo in treating fibromyalgia. A larger number of Savella-treated patients experienced at least a 30% reduction in pain from baseline as well meeting the criteria for a treatment response as measured by improvements in pain, physical function, and patient global assessment (4, 5).Savella (milnacipran) joins the ranks of Lyrica and Cymbalta as FDA-approved treatments of fibromyalgia and will give clinicians another treatment option for this disease.

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Comparison of Amitriptyline and US Food and Drug Administration–Approved Treatments for Fibromyalgia

et al. 2022

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IMPORTANCE Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia. OBJECTIVE To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.

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The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial

Abstract: Milnacipran is safe and effective for the treatment of multiple symptoms of FM.

Cited by 240 publications

References 52 publications

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

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

ACS Chemical Neuroscience Molecule Spotlight on Savella

Comparison of Amitriptyline and US Food and Drug Administration–Approved Treatments for Fibromyalgia

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