title: Milnacipran for neuropathic pain and fibromyalgia in adults.
abstract: BACKGROUND
  Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia.
  
  
  OBJECTIVE
  To evaluate the analgesic efficacy and adverse effects of milnacipran in the management of chronic neuropathic pain or fibromyalgia.
  
  
  METHODS
  We searched CENTRAL, MEDLINE, and EMBASE to 4th of January 2012, together with reference lists of retrieved papers and reviews.
  
  
  METHODS
  We included randomised, double-blind studies of eight weeks duration or longer, comparing milnacipran with placebo or another active treatment in chronic neuropathic pain or fibromyalgia.
  
  
  METHODS
  We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently.
  
  
  RESULTS
  Five studies (4138 participants) were included, all of which were placebo-controlled, involved participants with fibromyalgia, and used titration to a target dose of 100 mg or 200 mg milnacipran. There were no other active comparators or studies in other neuropathic pain conditions. Study quality was generally good, although the imputation method used in analyses of the primary outcomes could overestimate treatment effect.Both doses of milnacipran provided moderate levels of pain relief to about 40% of those treated, compared to 30% with placebo, giving a number needed to treat of 8 to 10. Adverse events were common in both milnacipran (87%) and placebo (78%) groups, but serious adverse events (< 2%) did not differ between groups. Nausea and constipation were the most common events showing the greatest difference between groups (number needed to treat for an additional harmful outcome of 7 and 13 respectively, compared with placebo).Withdrawals for any reason were more common with milnacipran than placebo, and more common with 200 mg than 100 mg (NNH of 23 and 8.8 respectively, compared with placebo). This was largely driven by adverse event withdrawals, where the NNH compared with placebo was 14 for 100 mg, and 7.0 for 200 mg). Withdrawals due to lack of efficacy were more common with milnacipran than placebo but did not differ between doses (number needed to treat to prevent an additional unwanted outcome of 45 and 41 respectively).
  
  
  CONCLUSIONS
  The evidence available indicates that milnacipran 100 mg or 200 mg is effective for a minority in the treatment of pain due to fibromyalgia, providing moderate levels of pain relief (at least 30%) to about 40% of participants, compared with about 30% with placebo. There were insufficient data to assess substantial levels of pain relief (at least 50%), and the use of last observation carried forward imputation may overestimate drug efficacy. Milnacipran is associated with increased adverse events and adverse event withdrawals, which were significantly greater for the higher dose. There were no data for the use of milnacipran for other chronic neuropathic pain conditions.
authors.affiliation: Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Oxford,UK. sheena.derry@pru.ox.ac.uk.
authors.forename: Sheena
authors.initials: S
authors.lastname: Derry
authors.forename: Dipender
authors.initials: D
authors.lastname: Gill
authors.forename: Tudor
authors.initials: T
authors.lastname: Phillips
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Moore
mesh_terms: D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use*; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D000078764:Milnacipran; D009437:Neuralgia / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors