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A prospective, open-label study of milnacipran in the prevention of headache in patients with episodic or chronic migraine

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Abstract

Migraine is a highly prevalent episodic and chronic neurological disorder that impacts otherwise healthy men and women in their most productive years. An anecdotal survey in our clinical practices suggested that milnacipran, a drug indicated for the treatment of fibromyalgia, reduced the incidence of headache in patients with migraine. In this 3-month, open-label, pilot study, 38 patients diagnosed with episodic migraine and 7 patients with chronic migraine maintained headache diaries to assess the effectiveness and tolerability of milnacipran in headache prevention. After a 1-month period to obtain baseline data, milnacipran treatment was initiated and doses were titrated up to 100 mg/day over 1 month. Maintenance therapy continued for an additional 3 months. The primary efficacy end point was change from baseline in the number of all headache days during the last 28 days of maintenance therapy analyzed, using last observation carried forward (LOCF). Change from baseline in migraine days during the last month of the maintenance period using LOCF was a secondary end point. Milnacipran 100 mg daily was associated with a significant reduction in headache (−4.2 days; P < 0.001) and migraine frequency (−2.2 days; P < 0.003). The adverse event profile was consistent with prior reports of milnacipran for the treatment of other conditions. However, compared with the recommended protocol, a more gradual increase in milnacipran dose was required to improve tolerability for some patients. The robust efficacy signal found in this study strongly suggests that a double-blind, placebo-controlled trial of milnacipran in migraine and chronic headache is warranted.

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References

  1. Lipton RB, Stewart WF, Diamond S et al (2001) Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 41:646–657

    Article  CAS  PubMed  Google Scholar 

  2. Forssman B, Henriksson K-G, Johannsson V et al (1976) Propranolol for migraine prophylaxis. Headache 16(5):238–245

    Article  CAS  PubMed  Google Scholar 

  3. Stellar S, Ahrens SP, Meibohm AR et al (1984) Migraine prevention with timolol: a double-blind crossover study. JAMA 252(18):2576–2580

    Article  CAS  PubMed  Google Scholar 

  4. Hering R, Kuritzky A (1992) Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 12:81–84

    Article  CAS  PubMed  Google Scholar 

  5. Brandes JL, Saper JR, Diamond M et al (2004) Topiramate for migraine prevention. A randomized, controlled trial. JAMA 291(8):965–973

    Article  CAS  PubMed  Google Scholar 

  6. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society (2012) Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 278:1337–1345

    Article  Google Scholar 

  7. Pringsheim T, Davenport WJ, Becker WJ (2010) Prophylaxis of migraine headache. CMAJ 182:E269–E276

    Article  PubMed Central  PubMed  Google Scholar 

  8. Berger A, Bloudek LM, Varon SF, Oster G (2012) Adherence with migraine prophylaxis in clinical practice. Pain Pract 12(7):541–549

    Article  PubMed  Google Scholar 

  9. Pompili M, Serafini G, Innamorati M et al (2010) Patient outcome in migraine prophylaxis: the role of psychopharmacological agents. Patient Relat Outcome Meas 1:107–118

    Article  PubMed Central  PubMed  Google Scholar 

  10. Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B (2004) Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Clin Neurol Neurosurg 107(1):44–48

    Article  PubMed  Google Scholar 

  11. Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R (2005) The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache 45(2):144–152

    Article  PubMed  Google Scholar 

  12. Mease PJ, Clauw DJ, Gendreau RM et al (2009) The efficacy and safety of milnacipran for treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial. J Rheumatol 36:398–409

    Article  CAS  PubMed  Google Scholar 

  13. Branco JC, Zachrisson D, Perrot S et al (2010) A European multicenter randomized double-blind, placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. J Rheumatol 37:851–859

    Article  CAS  PubMed  Google Scholar 

  14. Ormseth M, Eyler A, Hammonds C et al (2010) Milnacipran for the management of fibromyalgia syndrome. J Pain Res 3:15–24

    CAS  PubMed Central  PubMed  Google Scholar 

  15. US FDA. Good Clinical Practice Guidelines. Available at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/OfficeofScienceandHealthCoordination/ucm2018191.htm. Accessed July 17, 2013

  16. World Medical Association. Declaration of Helsinki. Available at: http://www.wma.net/en/30publications/10policies/b3/. Accessed July 17, 2013

  17. Stewart WF, Lipton RB, Kolodner KB, Sawyer J, Lee C, Liberman JN (2000) Validity of the Migraine Disability Assessment (MIDAS) score in comparison to a diary-based measure in a population sample of migraine sufferers. Pain 88:41–52

    Article  CAS  PubMed  Google Scholar 

  18. Beck AT, Steer RA (1987) The Beck Depression Inventory manual San Antonio: The Psychological Corporation, Harcourt Brace Jovanovich

  19. Johns M (1991) A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 14:540–545

    CAS  PubMed  Google Scholar 

  20. Ware JE Jr, Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A et al (1995) Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 33((4 Suppl)):AS264–AS279

    PubMed  Google Scholar 

  21. Lopez-Ibor J, Guelfi JD, Pletan Y et al (1996) Milnacipran and selective serotonin reuptake inhibitors in major depression. Int Clin Psychopharmacol 11(Suppl 4):41–46

    Article  PubMed  Google Scholar 

  22. Kasper S, Pail G (2010) Milnacipran: a unique antidepressant? Neuropsychiatr Dis Treat 6(Suppl 1):23–31

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Kohno T, Kimura M, Sasaki M et al (2012) Milnacipran inhibits glutamatergic N-Methyl-D-Aspartate receptor activity in Spinal Dorsal Horn Neurons. Mol Pain 8:45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Effexor [package insert] (2013) Wyeth Pharmaceuticals, Philadelphia, PA

  25. Gilman PK (2007) Tricyclic antidepressant pharmacology and therapeutic drug interaction. Br J Pharmacol 151(6):737–748

    Article  Google Scholar 

  26. Palmer RH, Periclou A, Banerjee P (2010) Milnacipran: a selective serotonin and norepinephrine dual reuptake inhibitor for the management of fibromyalgia. Ther Adv Musculoskelet Dis 2:201–220

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Estemalik E, Tepper S (2013) Preventive treatment in migraine and the new US guidelines. Neuropsychiatr Dis Treat 9:709–720

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Moskowitz MA, Nozaki K, Kraig RP (1993) Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within the trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci 13:1167–1177

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Lauritzen M, Hansen AJ (1992) The effect of Glutamate Receptor Blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab 12:223–229

    Article  CAS  PubMed  Google Scholar 

  30. Peeters M, Gunthorpe MJ, Strijbos PJ et al (2007) Effects of pan- and Subtype-selective N-methyl-D-aspartate receptor antagonists on cortical spreading depression in the rat: therapeutic potential for migraine. J Pharmacol Exp Ther 321(2):564–572

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Ann C Sherwood, Ph.D for editorial support in the preparation of this manuscript. This study was funded by a research grant from Forest Research Institute.

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Correspondence to Emily Rubenstein Engel.

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ClinicalTrials.gov Identifier: NCT01319825.

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Engel, E.R., Kudrow, D. & Rapoport, A.M. A prospective, open-label study of milnacipran in the prevention of headache in patients with episodic or chronic migraine. Neurol Sci 35, 429–435 (2014). https://doi.org/10.1007/s10072-013-1536-0

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  • DOI: https://doi.org/10.1007/s10072-013-1536-0

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