title: Milnacipran for treatment of fibromyalgia.
abstract: 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.
authors: Samford University, Birmingham, AL, USA. jakyle@samford.edu
authors: Jeffrey A
authors: JA
authors: Kyle
authors: B Deeann
authors: BD
authors: Dugan
authors: Kristian K
authors: KK
authors: Testerman
mesh_terms: 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*
chemical_list: D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors