Milnacipran for treatment of fibromyalgia.
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and safety of milnacipran and evaluate relevant clinical trial data.


METHODS
MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1966-June 2010) were conducted using the key words fibromyalgia, milnacipran, and serotonin-norepinephrine reuptake inhibitor. Searches were limited to articles published in English.


METHODS
All available English-language articles of human studies were evaluated. One pharmacokinetic study reviewed included animal data. References cited in identified articles were used for additional evaluation.


RESULTS
Milnacipran is a serotonin-norepinephrine reuptake inhibitor with a 3-fold increased selectivity for norepinephrine compared to serotonin. It is well absorbed with 85-90% bioavailability. Maximum concentrations are achieved 2-4 hours after administration. Milnacipran does not undergo cytochrome P450 metabolism and has a half-life of 6-8 hours. Fifty-five percent of each dose is excreted unchanged in the urine. Dose adjustment is needed in patients with an estimated creatinine clearance of <30 mL/min. Clinical trials indicated that twice-daily dosing at 100 mg/day or 200 mg/day was superior to single-daily dosing. Studies further established the effectiveness of both doses in the treatment of fibromyalgia pain utilizing patient self-reported pain scores, as well as on a visual analog scale, Patient Global Impression of Change scale, and the Short-Form 36 Physical Component Summary. A 6-month extension trial, which evaluated patients continued on milnacipran for up to 1 year, demonstrated continued pain relief. The most common adverse drug reaction associated with milnacipran was nausea, which was reduced with slow-dose titration and administration with food.


CONCLUSIONS
Milnacipran is an effective treatment option for patients with fibromyalgia. More head-to-head clinical trials are necessary to assess its ultimate place in therapy.
Kyle
Jeffrey A
JA
Samford University, Birmingham, AL, USA. jakyle@samford.edu
Dugan
B Deeann
BD
Testerman
Kristian K
KK
D000818:Animals; D003521:Cyclopropanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors