Drug Design, Development and Therapy (Aug 2018)

Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study

  • Pickering G,
  • Macian N,
  • Delage N,
  • Picard P,
  • Cardot JM,
  • Sickout-Arondo S,
  • Giron F,
  • Dualé C,
  • Pereira B,
  • Marcaillou F

Journal volume & issue
Vol. Volume 12
pp. 2485 – 2496

Abstract

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Gisèle Pickering,1,2 Nicolas Macian,2 Noémie Delage,3 Pascale Picard,3 Jean-Michel Cardot,4 Sophia Sickout-Arondo,2 Fatiha Giron,2 Christian Dualé,2 Bruno Pereira,5 Fabienne Marcaillou3 1University Clermont Auvergne Neurodol, Clermont-Ferrand, France; 2Clinical Pharmacology Department CPC/CIC Inserm 1405, University Hospital, Clermont-Ferrand, France; 3Pain Clinic, CHU Clermont-Ferrand, Clermont-Ferrand, France; 4University Clermont Auvergne MEDIS, CHU Clermont-Ferrand, Clermont-Ferrand, France; 5DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France Introduction: Fibromyalgia is characterized by widespread and chronic pain, and its prevalence is increasing worldwide. Milnacipran, an antidepressant, is often prescribed for fibromyalgia with a possible beneficial effect on central pain modulation. The aim of this study was to evaluate if milnacipran could modify the status of conditioned pain modulation (CPM) in patients suffering from fibromyalgia.Design and setting: Randomized, double-blind controlled trial.Subjects and methods: Women with fibromyalgia received milnacipran 100 mg or placebo. The primary end point was the evolution of CPM with treatments after a 30-second painful stimulus. Secondary outcomes included the predictability of milnacipran efficacy from CPM performance, evolution of global pain, mechanical sensitivity, thermal pain threshold, mechanical allodynia, cognitive function, and tolerance.Results: Fifty-four women with fibromyalgia (46.7±10.6 years) were included and randomized, and 24 patients were analyzed in each group. At inclusion, CPM was dysfunctional (CPM30=-0.5±1.9), and global pain was 6.5±1.8. After treatment, there was a nonsignificant CPM difference between milnacipran and placebo (CPM30=-0.46±1.22 vs -0.69±1.43, respectively, p=0.55) and 18.8% vs 6.3% (p=0.085) patients did reactivate CPM after milnacipran vs placebo. Initial CPM was not a predictor of milnacipran efficacy. Global pain, mechanical and thermal thresholds, allodynia, cognition, and tolerance were not significantly different between both groups.Conclusion: Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnacipran to reactivate CPM in a number of patients must be explored with longer treatment duration in future studies and pleads for possible subtypes of fibromyalgia patients. Keywords: fibromyalgia, CPM, milnacipran, antidepressants, pain 

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