NCT01393522.

Trial name or title	SAV‐MD‐25 Title: A randomized double blind placebo control trial of milnacipran for migraine pain
Methods	Allocation: randomised Intervention model: parallel assignment Masking: double‐blind (subject, investigator) Primary purpose: to evaluate the efficacy of milnacipran in headache pain reduction in subjects with chronic migraine (CM) without fibromyalgia
Participants	Inclusion criteria: Individuals between the age of 18 and 65, both genders Headache fulfils ICHD‐2 criteria for: chronic migraine, or probable medication overuse headache where individual headaches meet criteria for migraine At least 15 headache days/month and at least 8 migraine or probable migraine days/month for the past 3 months, by patient report (including days of headache relieved with a triptan or related compound) Age at onset of chronic migraine < 60 years old Main exclusion criteria: Subject has failed >/= 4 adequate preventive trials of antidepressant medications due to lack of efficacy; at least 1 trial included another SNRI. (An adequate preventive trial defined as at least 6 weeks on therapeutic dose (150 mg of amitriptyline or nortriptyline or other tricyclic, 150 mg of venlafaxine, 60 mg of duloxetine)) Subjects on antidepressant medications, including SNRIs who cannot safely withdraw from those medications, in the assessment of the PI. Subjects on other headache preventives (beta‐blockers, antiepileptic drugs), at a stable dose for at least 3 months, will be allowed to participate Presence of fibromyalgia or another pain or medical disorder that would make it difficult for the patient to distinguish headache‐related quality of life from overall health‐related quality of life
Interventions	Intervention: milnacipran titration schedule starting with 12.5 mg per day increasing to 50 mg twice a day, starting with day 1 to day 90 and then tapered down Control: placebo titrated 1 tablet once a day increased per protocol to 2 tablets twice a day, with a starting dose of 12.5 mg per day to 50 mg twice a day
Outcomes	Evaluating Headache Pain Reduction (time frame: change from baseline after the 90‐day reporting period) Evaluating the improvement of Quality of Life (time frame: change from visit 1 until study completion month 4)
Starting date	June 2011
Contact information	Timothy R Smith, MD; mercyhealthresearch@mercy.net
Notes	Study sponsor: Mercy Health Research Recruitment status: recruiting (verification date: September 2011)

ICHD‐2: International Classification of Headache Disorders: 2nd edition
 PI: principal investigator
 SNRI: serotonin‐norepinephrine reuptake inhibitor