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Meta-Analysis
. 2012 Mar 14;3(3):CD008244.
doi: 10.1002/14651858.CD008244.pub2.

Milnacipran for neuropathic pain and fibromyalgia in adults

Sheena Derry  1 , Dipender Gill, Tudor Phillips, R Andrew Moore
Affiliations
Meta-Analysis

Milnacipran for neuropathic pain and fibromyalgia in adults

Sheena Derry et al. Cochrane Database Syst Rev. .

Update in

  • Milnacipran for pain in fibromyalgia in adults.
    Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Cording M, et al. Cochrane Database Syst Rev. 2015 Oct 20;2015(10):CD008244. doi: 10.1002/14651858.CD008244.pub3. Cochrane Database Syst Rev. 2015. PMID: 26482422 Free PMC article.

Abstract

Background: Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia.

Objectives: To evaluate the analgesic efficacy and adverse effects of milnacipran in the management of chronic neuropathic pain or fibromyalgia.

Search methods: We searched CENTRAL, MEDLINE, and EMBASE to 4th of January 2012, together with reference lists of retrieved papers and reviews.

Selection criteria: 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.

Data collection and analysis: We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently.

Main 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).

Authors' 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.

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Figures

Figure 1
Figure 1
‘Risk of bias’ graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.
Figure 2
Figure 2
‘Risk of bias’ summary: review authors’ judgements about each risk of bias item for each included study.
Figure 3
Figure 3
Forest plot of comparison: 1 Milnacipran 100 mg/day versus placebo, outcome: 1.1 At least 30% pain relief.
Figure 4
Figure 4
Forest plot of comparison: 1 Milnacipran 100 mg/day versus placebo, outcome: 1.7 Individual adverse events.
See this image and copyright information in PMC

References

References to studies included in this review

    1. Arnold LM, Gendreau RM, Palmer RH, Gendreau JF, Wang Y. Efficacy and safety of milnacipran 100mg/day in patients with fibromyalgia. Arthritis and Rheumatism. 2010;62(9):2745–56. - PubMed
    1. Branco JC, Zachrisson O, Perrot S, Mainguy Y. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. Journal of Rheumatology. 2010;37(4):851–9. - PubMed
    1. Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y. Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Clinical Therapeutics. 2008;30(11):1988–2004. - PubMed
    1. Mease PJ, Clauw DJ, Gendreau RM, Rao SG, Kranzler J, Chen W, et al. The efficacy and safety or milnacipran for treatment of fibromyalgia. A randomized, double-blind, placebo-controlled trial. Journal of Rheumatology. 2009;36(2):398–409. - PubMed
    1. Gendreau RM, Thorn MD, Gendreau JF, Kranzler JD, Ribeiro S, Gracely RH, et al. Efficacy of milnacipran in patients with fibromyalgia. Journal of Rheumatology. 2005;32:1975–85. - PubMed
    2. Vitton O, Gendreau M, Gendreau J, Kranzler J, Rao SG. A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Human Psychopharmacology. 2004;19:S27–S35. - PubMed

References to studies excluded from this review

    1. Branco JC, Cherin P, Montagne A, Bouroubi A, on behalf of the Multinational Coordinator Study Group Longterm therapeutic response to milnacipran treatment for fibromyalgia. A European 1-year extension study following a 3-month study. Journal of Rheumatology. 2011;38(7):1403–12. [DOI: 10.3899/jrheum.101025] - PubMed
    1. Goldenberg DL, Clauw DJ, Palmer RH, Mease P, Chen W, Gendreau RM. Durability of therapeutic response to milnacipran treatment for fibromyalgia. Results of a randomized, double-blind, monotherapy 6-month extension study. Pain Medicine. 2010;11(2):180–94. - PubMed
    1. [accessed 12 August 2011];A multicenter, randomized, open-label, controlled study to evaluate the safety, tolerability, and efficacy of milnacipran when added to pregabalin in the treatment of fibromyalgia. 2011 http://clinicaltrials.gov/ct2/show/NCT00797797?term=milnacipran&rank=18.

References to ongoing studies

    1. [accessed 12 August 2011];An exploratory randomized placebo controlled trial of milnacipran in patients with chronic neuropathic low back pain. http://clinicaltrials.gov/ct2/show/NCT01225068?term=milnacipran&rank=24.
    1. [accessed 12 August 2011];A placebo controlled, randomized, double blind trial of milnacipran for the treatment of idiopathic neuropathy pain. http://clinicaltrials.gov/ct2/show/NCT00797797?term=milnacipran&rank=18.

Additional references

    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain. 2008;9(2):105–21. [DOI: 10.1016/j.jpain.2007.09.005] - PubMed
    1. Gustorff B, Dorner T, Likar R, Grisold W, Lawrence K, Schwarz F, et al. Prevalence of self-reported neuropathic pain and impact on quality of life: a prospective representative survey. Acta Anaesthesiologica Scandinavica. 2008;52(1):132–6. - PubMed
    1. Hall GC, Carroll D, Parry D, McQuay HJ. Epidemiology and treatment of neuropathic pain: the UK primary care perspective. Pain. 2006;122(1-2):156–62. [DOI: 10.1016/j.pain.2006.01.030] - PubMed
    1. Häuser W, Petzke F, Sommer C. Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. Journal of Pain. 2010;11(6):505–21. - PubMed
    1. Häuser W, Petzke F, Üçeyler N, Sommer C. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis. Rheumatology (Oxford) 2011;50(3):532–43. [DOI: 10.1093/rheumatology/keq354] - PubMed

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