Milnacipran for the management of fibromyalgia syndrome

Figures & data

Table 1 Relative 5-HT:NE In-vitro reuptake inhibition of SNRI-active drugs

Drug name	5-HT:NE reuptake inhibition ratio
Venlafaxine	30:1
Duloxetine	10:1
Desvenlafaxine	10:1
Amitriptyline	8:1
Milnacipran	1:1

Used with permission from Scholtz BA, Hammonds CL, Boomershine CS. Duloxetine for the management of fibromyalgia syndrome. J Pain Res. 2009; 2:99–108.²² Copyright © 2009 Dove Medical Press.

Abbreviations: 5-HT, serotonin; NE, norepinephrine; SNRI, serotonin–norepinephrine reuptake inhibitor.

Table 2 Overview of published milnacipran fibromyalgia treatment trials

Milnacipran study	Subject number, allocation, dosing and duration	Placebo and milnacipran completion rates (%)	Mean age; mean disease duration; % female; % caucasian	Primary efficacy measure(s) and analysis	Study met primary efficacy measure?	Milnacipran effect versus placebo on improving symptoms?	% Patients significant pain improvement vs placebo	% Patients significant PGIC improvement vs placebo	SeriousTEAE and drop out due to TEAE rates
Study 1: Vitton et al^Citation34	125 2:3:3	Placebo 75% Milnacipran 71.1%	47 yrs; 4.15 yrs;	2-week average daily pain score by e-diary using Gracely logarithmic pain scale LOCF analysis	BID dose group only	Pain (yes), global status (yes), QOL (no), fatigue (yes), stiffness (yes), physical function (yes), sleep (no), sexual function (no)	Only BID dosing group: ≥30% improvement: 39% BID vs 14% placebo ≥50% improvement: 37% BID vs 14% placebo	Both BID and QD dosing groups significant: 73% BID 77% QD 38% placebo	Serious TEAE rate: 0% for all groups Drop out rates: 21.7% QD, 13.7% BID, 3.6% placebo
Study 2: Gendreau et al^Citation35	Placebo:QD:BID Maximum tolerated dose to 200 mg/day divided QD or BID 12 weeks		97%; 85%
Study 3: Clauw et al^Citation36	1196 1:1:1 Placebo:100:200 Fixed dose 100 or 200 mg divided BID 15 weeks	Placebo 72.3% Milnacipran 65.5%	50.2 yrs; NR; 96.2%; 93.5%	Treatment Composite Response (Pain + Global + Function) Pain Composite Response (Pain + Global) BOCF analysis	Yes, both milnacipran groups met both composite response endpoints	Pain (yes), global status (yes), physical function (yes), fatigue (yes), sleep (no), cognition (yes)	% ≥30% improvement: 52.3% (100 mg), 54.8% (200 mg), vs 38.4% (placebo) % ≥50% improvement NR	47.5% (100 mg), 50.6% (200 mg) vs 31.8% (placebo) PGIC “much improved” or “very much improved”	Serious TEAE rates: 1.3% 100 mg, 1% 200 mg, 1.5% placebo. Drop out rates: 19.5% 100 mg, 23.7% 200 mg, 9.5% placebo
Study 4: Mease et al^Citation33	888 1:1:2 Placebo:100:200 Fixed dose 100 or 200 mg divided BID 27 weeks	Placebo 65% Milnacipran 56%	49.5 yrs; 5.6 yrs; 95%; 94%.	Treatment Composite Response (Pain + Global + Function) Pain Composite Response (Pain + Global) Modified BOCF analysis	Pain Composite Response only in 200 mg/day group	Pain (yes), global status (yes), fatigue (yes), cognition (yes), sleep (no), sexual function (no)	% ≥30% improvement: 52.8% (100 mg), 56.2% (200 mg) vs 40.2% (placebo). % ≥50% improvement: 37% (200 mg) vs 26.2% (placebo)	27 week data not reported 15-week data: 76% (100 mg) and 78% (200 mg) vs 61% (placebo) with PGIC “much improved” to “very much improved”	Serious TEAE rates: 1.3% 100 mg, 2.5% 200 mg, 2.7% placebo Drop out rates: 19.6% 100 mg, 27% 200 mg, 10.3% Placebo

Abbreviations: BID, twice daily; BOCF, baseline observation carried forward; NR, not reported; QD, once daily; PGIC, Patient Global Impression of Change; TEAE, treatment emergent adverse event.

ScholtzBAHammondsCLBoomershineCSDuloxetine for the management of fibromyalgia syndromeJ Pain Res2009299108

 Google Scholar

VittonOGendreauMGendreauJKranzlerJRaoSGA double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgiaHum Psychopharmacol200419Suppl 1S27S3515378666

 PubMed Web of Science ®Google Scholar

GendreauRMThornMDGendreauJFKranzlerJDEfficacy of milnacipran in patients with fibromyalgiaJ Rheumatol2005321975198516206355

 PubMed Web of Science ®Google Scholar

ClauwDJMeasePPalmerRHGendreauRMWangYMilnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trialClin Ther2008301988200419108787

 PubMed Web of Science ®Google Scholar

MeasePJClauwDJGendreauRMThe efficacy and safety of milnacipran for treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trialJ Rheumatol20093639840919132781

 PubMed Web of Science ®Google Scholar