Neurological Sciences

, Volume 35, Supplement 1, pp 89–97 | Cite as

New treatments for headache

Key Note Lecture

Abstract

Migraine and cluster headache are primary headache disorders commonly encountered in clinical practice. Despite the profound disability caused by these primary headache disorders, available acute and preventive treatment options are limited. Recent understanding of headache pathophysiology has led to the development of new drug formulations and novel drug targets that are extremely promising. This article will highlight several of the new treatments that are currently under investigation including novel delivery mechanisms of already existing medications, calcitonin gene-related peptide (CGRP) receptor antagonists, antibodies to CGRP and its receptor, serotonin receptor agonists, transient receptor potential vanilloid receptor modulators, orexin receptor antagonists, glial cell modulators, and neuromodulation. If data is supportive, these therapies will be welcome additions to the headache specialist’s armamentarium.

Keywords

Migraine treatment Headache therapy pipeline Novel delivery mechanisms CGRP Neuromodulation 

References

  1. 1.
    Haut SR, Bigal ME, Lipton RB (2006) Chronic disorders with episodic manifestations: focus on epilepsy and migraine. Lancet Neurol 5:148–157PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Robbins MS, Lipton RB (2010) The epidemiology of primary headache disorders. Semin Neurol 30:107–119PubMedCrossRefGoogle Scholar
  3. 3.
    Ferrari MD, Roon KI, Lipton RB, Goadsby PJ (2001) Oral triptans (serotonin 5-HT (1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 358:1668–1675PubMedCrossRefGoogle Scholar
  4. 4.
    Johnston M, Rapoport A (2010) Triptans for the management of migraine. Drugs 70:1505–1518PubMedCrossRefGoogle Scholar
  5. 5.
    Brandes JL, Cady RK, Freitag FG, Smith TR, Chandler P, Fox AW et al (2009) Needle-free subcutaneous sumatriptan (Sumavel(™) DosePro(™)): bioequivalence and ease of use. Headache 49:1435–1444PubMedCrossRefGoogle Scholar
  6. 6.
    Rothrock JF, Cady RK, Aurora SK, Brandes JL, Meyers JA, Fox AW et al (2011) Needle-free subcutaneous sumatriptan for triptan users requiring a change in migraine therapy: efficacy and impact on patient-related functionality, satisfaction, and confidence. Curr Med Res Opin 27:2185–2191PubMedCrossRefGoogle Scholar
  7. 7.
    Cady RK, Aurora SK, Brandes JL, Rothrock JF, Myers JA, Fox AW et al (2011) Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans. Headache 51:1202–1211PubMedCrossRefGoogle Scholar
  8. 8.
    Landy SH, Tepper SJ, Wein T, Schweizer E, Ramos E (2013) An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan. Headache 53:118–125PubMedCrossRefGoogle Scholar
  9. 9.
    Vikelis M, Mitsikostas D, Rapoport AM (2012) Sumatriptan transdermal iontophoretic patch (NP101—Zelrix(™)): review of pharmacology, clinical efficacy, and safety in the acute treatment of migraine. Neuropsychiatr Dis Treat 8:429–434PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Goldstein J, Smith TR, Pugach N, Griesser M, Sebree T, Pierce M (2012) A sumatriptan iontophoretic transdermal system for the acute treatment of migraine. Headache 52:1402–1410PubMedCrossRefGoogle Scholar
  11. 11.
    Siegel SJ, O’Neill CO, Dube LM, Kaldeway P, Morris R, Jackson D et al (2007) A unique iontophoretic patch for optimal transdermal delivery of sumatriptan. Pharm Res 24:1919–1926PubMedCrossRefGoogle Scholar
  12. 12.
    Pierce M, Marbury T, O’Neill C, Siegel S, Du W, Sebree T (2009) Zelrix(™): a novel transdermal formulation of sumatriptan. Headache 49:817–825PubMedCrossRefGoogle Scholar
  13. 13.
    Smith TR, Goldstein J, Singer R, Pugach N, Silberstein S, Pierce MW (2012) Twelve-month tolerability and efficacy study of NP101, the sumatriptan iontophoretic transdermal system. Headache 52:612–624PubMedCrossRefGoogle Scholar
  14. 14.
    Luthringer R, Djupesland PG, Sheldrake CD, Flint A, Boeijinga P, Danjou P et al (2009) Rapid absorption of sumatriptan powder and effects on glyceryl trinitrate model of headache following intranasal delivery using a novel bi-directional device. J Pharm Pharmacol 61:1219–1228PubMedCrossRefGoogle Scholar
  15. 15.
    Djupesland PG, Docekal P, Czech Migraine Investigators G (2010) Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: a randomised, placebo-controlled study. Cephalalgia 30:933–942PubMedGoogle Scholar
  16. 16.
    Tepper SJ (2013) Clinical implications for breath-powered powder sumatriptan intranasal treatment. Headache 53:1341–1349PubMedCrossRefGoogle Scholar
  17. 17.
    Djupesland PG, Messina JC, Mahmoud RA (2013) Breath powered nasal delivery: a new route to rapid headache relief. Headache 53(suppl 2):72–84PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Diener H-C, Montagna P, Gàcs G, Lyczak P, Schumann G, Zoller B et al (2006) Efficacy and tolerability of diclofenac potassium sachets in migraine: a randomized, double-blind, cross-over study in comparison with diclofenac potassium tablets and placebo. Cephalalgia 26:537–547PubMedCrossRefGoogle Scholar
  19. 19.
    Lipton RB, Grosberg B, Singer RP, Pearlman SH, Sorrentino JV, Quiring JN et al (2010) Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: results from the international migraine pain assessment clinical trial (IMPACT). Cephalalgia 30(11):1336–1345PubMedCrossRefGoogle Scholar
  20. 20.
    Boureau F, Kappos L, Schoenen J, Esperanca P, Ashford E (2010) A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine. Int J Clin Pract 54:281–286Google Scholar
  21. 21.
    Silberstein S (2012) MAP0004: dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine. Expert Opin Pharmacother 13:1961–1968PubMedCrossRefGoogle Scholar
  22. 22.
    Shrewsbury SB, Cook RO, Taylor G, Edwards C, Ramadan NM (2008) Safety and pharmacokinetics of dihydroergotamine mesylate administered via a Novel (Tempo(™)) Inhaler. Headache 48:355–367PubMedCrossRefGoogle Scholar
  23. 23.
    Aurora SK, Rozen TD, Kori SH, Shrewsbury SB (2009) A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache 49:826–837PubMedCrossRefGoogle Scholar
  24. 24.
    Aurora SK, Silberstein SD, Kori SH, Tepper SJ, Borland SW, Wang M et al (2011) MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine. Headache 51:507–517PubMedCrossRefGoogle Scholar
  25. 25.
    Burstein R, Collins B, Jakubowski M (2004) Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 55:19–26PubMedCrossRefGoogle Scholar
  26. 26.
    Burstein R, Jakubowski M (2004) Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol 55:27–36PubMedCrossRefGoogle Scholar
  27. 27.
    Tepper SJ, Kori SH, Borland SW, Wang MH, Hu B, Mathew NT et al (2012) Efficacy and safety of MAP0004, orally inhaled DHE in treating migraine with and without allodynia. Headache 52:37–47PubMedCrossRefGoogle Scholar
  28. 28.
    Goadsby PJ, Edvinsson L (1993) The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 33:48–56PubMedCrossRefGoogle Scholar
  29. 29.
    Tajti J, Uddman R, Moller S, Sundler F, Edvinsson L (1999) Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst 76:176–183PubMedCrossRefGoogle Scholar
  30. 30.
    Eftekhari S, Salvatore CA, Calamari A, Kane SA, Tajti J, Edvinsson L (2010) Differential distribution of calcitonin gene related peptide and its receptor components in the human trigeminal ganglion. Neuroscience 169:683–696PubMedCrossRefGoogle Scholar
  31. 31.
    Edvinsson L, Gulbenkian S, Barrosco CP, Cunha e Sa M, Polack JM, Mortensen A et al (1998) Innervation of the human middle meningeal artery: immunohistochemistry, ultrastructure, and role of endothelium for vasomotility. Peptides 19:1213–1225PubMedCrossRefGoogle Scholar
  32. 32.
    Storer RJ, Akerman S, Goadsby PJ (2004) Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br J Pharmacol 142:1171–1181PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Goadsby PJ (2007) Recent advances in understanding migraine mechanisms, molecules, and therapeutics. Trends Mol Med 13:39–44PubMedCrossRefGoogle Scholar
  34. 34.
    Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U et al (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104–1110PubMedCrossRefGoogle Scholar
  35. 35.
    Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ et al (2008) Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology 70:1304–1312PubMedCrossRefGoogle Scholar
  36. 36.
    Hewitt DJ, Martin V, Lipton RB, Brandes J, Ceesay P, Gottwald R et al (2011) Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine. Headache 51:533–543PubMedCrossRefGoogle Scholar
  37. 37.
    Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X et al (2008) Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomized, placebo-controlled, parallel-treatment trial. Lancet 372:2115–2123PubMedCrossRefGoogle Scholar
  38. 38.
    Connor KM, Shapiro RE, Diener HC, Lucus S, Kost J, Fan X et al (2009) Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology 73:970–977PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Hewitt DJ, Aurora SK, Dodick DW, Goadsby PJ, Ge YJ, Bachman R et al (2011) Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 31:712–722PubMedCrossRefGoogle Scholar
  40. 40.
    Ho TW, Ho AP, Chaitman BR, Johnson C, Mathew NT, Kost J et al (2012) Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease. Headache 52:224–235PubMedCrossRefGoogle Scholar
  41. 41.
    van der Schueren BJ, Blanchard R, Murphy MG, Palcza J, De Lepeleire I, Van Hecken A et al (2010) The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol 71:708–717CrossRefGoogle Scholar
  42. 42.
    Ho AP, Dahlof CG, Silberstein SD, Saper JR, Ashina M, Kost JT et al (2010) Randomized, controlled trial of telcagepant over four migraine attacks. Cephalalgia 30:1443–1457PubMedCrossRefGoogle Scholar
  43. 43.
    Connor KM, Aurora SK, Loeys T, Ashina M, Jones C, Giezek H et al (2011) Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial. Headache 51:73–84PubMedCrossRefGoogle Scholar
  44. 44.
    Ho TW, Olesen J, Dodick DW, Kost J, Lines C, Ferrari MD (2011) Antimigraine efficacy of telcagepant based on patient’s historical triptan response. Headache 51:64–72PubMedCrossRefGoogle Scholar
  45. 45.
    Hoffmann J, Goadsby PJ (2012) New agents for acute treatment of migraine: CGRP receptor antagonists, iNOS inhibitors. Curr Treat Options Neurol 14:50–59PubMedCrossRefGoogle Scholar
  46. 46.
    Han TH, Blanchard RL, Palcza J, McCrea JB, Laethem T, Willson K et al (2010) Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults. J Clin Pharmacol 50:1367–1376PubMedCrossRefGoogle Scholar
  47. 47.
    Diener HC, Barbanti P, Dahlof C, Reuter U, Habeck J, Podhorna J (2011) BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine: results from a phase II study. Cephalalgia 31:573–584PubMedCrossRefGoogle Scholar
  48. 48.
    Marcus R, Goadsby PJ, Dodick D, Stock D, Manos G, Fischer TZ (2014) BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia 34:114–125PubMedCrossRefGoogle Scholar
  49. 49.
    A dose-finding study of MK-1602 in the treatment of acute migraine (MK-1602-006 AM1). NCT01613248. http://www.clinicaltrials.gov/ct2/show/NCT01613248. Accessed 20 Feb 2014
  50. 50.
    A safety, tolerability, and pharmacokinetic study of single, escalating subcutaneous doses of LY2951742 in healthy volunteers. NCT01337596. http://www.clinicaltrials.gov/ct2/show/NCT01337596. Accessed 13 Feb 2014
  51. 51.
    A phase 2, randomized, double-blind, placebo-controlled study of LY2951742 in patients with migraine. NCT10625988. http://www.clinicaltrials.gov/ct2/show/NCT01625988. Accessed 13 Feb 2014
  52. 52.
    A single-dose, placebo-controlled, ascending dose study to determine the safety, tolerability, and pharmacokinetics of ALD403, a humanized anti-calcitonin gene-related peptide monoclonal antibody administered by intravenous infusion and subcutaneous injection. NCT10579383. http://www.clinicaltrials.gov/ct2/show/NCT01579383. Accessed 13 Feb 2014
  53. 53.
    A parallel group, soluble-blind, randomized, placebo controlled phase 1b trial to evaluate the safety, pharmacokinetics, and efficacy of a single dose of ALD403 administered intravenously in patients with frequent episodic migraines. NCT017772524. http://www.clinicaltrials.gov/ct2/show/NCT01772524. Accessed 13 Feb 2014
  54. 54.
    Bigal ME, Escandon R, Bronson M, Walter S, Sudwoth M, Huggins JP, et al (2013) Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: results of the phase I program. Cephalalgia [Epub ahead of print]Google Scholar
  55. 55.
    A randomized, placebo-controlled, double-blind, parallel group study assessing the safety, tolerability, and pharmacokinetics of two different doses of LBR-101 given intravenously and subcutaneously. NCT01991509. http://www.clinicaltrials.gov/ct2/show/NCT01991509. Accessed 13 Feb 2014
  56. 56.
    A multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group, multi-dose study comparing the efficacy and safety of subcutaneous LBR-101 with placebo for the preventive treatment of chronic migraine. NCT02021773. http://www.clinicaltrials.gov/ct2/show/NCT02021773. Accessed 13 Feb 2014
  57. 57.
    A multicenter, randomized, double-blind, placebo-controlled, parallel-group, study comparing the efficacy and safety of two doses of subcutaneous LBR-101 with placebo for the preventive treatment of high frequency episodic migraine. NCT02025556. http://www.clinicaltrials.gov/ct2/show/NCT02025556. Accessed 13 Feb 2014
  58. 58.
    Bigal ME, Walter S, Rapoport AM (2013) Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development. Headache 53:1230–1244PubMedCrossRefGoogle Scholar
  59. 59.
    A phase I, randomized, double-blind, placebo-controlled, ascending single dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 334 in healthy subjects and migraine patients. NCT01688739. http://www.clinicaltrials.gov/ct2/show/NCT01688739. Accessed 13 Feb 2014
  60. 60.
    Phase 1, randomized, double-blind, placebo-controlled, ascending multiple-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 334 in healthy subjects and in migraine patients. NCT01723514. http://www.clinicaltrials.gov/ct2/show/NCT01723514. Accessed 13 Feb 2014
  61. 61.
    A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of AMG 334 in migraine prevention. NCT01952574. http://www.clinicaltrials.gov/ct2/show/NCT01952574. Accessed 13 Feb 2014
  62. 62.
    A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of AMG 334 in chronic migraine prevention. NCT02066415. http://www.clinicaltrials.gov/ct2/show/NCT02066415. Accessed 21 Feb 2014
  63. 63.
    Neeb L, Meents J, Reuter U (2010) 5-HT-1F receptor agonists: a new treatment option for migraine attacks? Neurotherapeutics 7:176–182PubMedCrossRefGoogle Scholar
  64. 64.
    Nelson DL, Phebus LA, Johnson KW (2010) Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmitidan. Cephalalgia 30:1159–1169PubMedCrossRefGoogle Scholar
  65. 65.
    Ferrari MD, Farkkila M, Reuter U, Pilgrim A, Davis C, Krauass M (2010) Acute treatment of migraine with the selective 5-HT-1F receptor agonist lasmitidan—a randomised proof-of-concept trial. Cephalalgia 30:1170–1178PubMedCrossRefGoogle Scholar
  66. 66.
    Fakkila M, Diener HC, Geraud G, Laniz JM, Schoenen J, Pilgrim AJ (2010) Lasmitidan (COL-144), a selective 5HT1F agonist, is a rapid and effective oral treatment for acute migraine. J Headache Pain 11(Suppl 1):S43Google Scholar
  67. 67.
    Jansen-Olesen I, Mortensen A, Edvinsson L (1996) Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilation of human cerebral arteries concomitant with activation of adenylyl cyclase. Cephalalgia 16:310–316PubMedCrossRefGoogle Scholar
  68. 68.
    Rapoport AM (2012) The therapeutic future in headache. Neurol Sci 22(Suppl 1):S119–S125CrossRefGoogle Scholar
  69. 69.
    Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, Bernstein JE (2002) Intranasal civamide for the treatment of episodic cluster headache. Arch Neurol 59:990–994PubMedCrossRefGoogle Scholar
  70. 70.
    Civamide nasal solution for cluster headache (ECH). NCT01341548. http://clinicaltrials.gov/ct2/show/NCT01341548. Accessed 26 Feb 2013
  71. 71.
    Diamond S, Freitag F, Phillips SB, Bernstein JE, Saper JR (2000) Intranasal civamide for the acute treatment of migraine headache. Cephalalgia 20:597–602PubMedCrossRefGoogle Scholar
  72. 72.
    Bartsch T, Levy MJ, Knight YE, Goadsby PJ (2004) Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain 109:367–378PubMedCrossRefGoogle Scholar
  73. 73.
    Holland PR, Akerman S, Goadsby PJ (2006) Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci 24:2825–2833PubMedCrossRefGoogle Scholar
  74. 74.
    Winrow CJ, Gotter AL, Cox CD, Tannenbaum PL, Garson SL, Doran SM et al (2012) Pharmacololgical characterization of MK-6096—a dual orexin receptor antagonist for insomnia. Neuropharmacology 62:978–987PubMedCrossRefGoogle Scholar
  75. 75.
    A study of the safety and efficacy of MK-6096 for migraine prophylaxis in participants with episodic migraine (MK-6096-020). NCT01513291. http://clinicaltrials.gov/ct2/show/NCT01513291. Accessed 26 Feb 2013
  76. 76.
    Hanani M (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev 48:457–476PubMedCrossRefGoogle Scholar
  77. 77.
    Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, Freeman SE et al (2007) Neuron–Glia signaling in trigeminal ganglion: implications for migraine pathology. Headache 47:1008–1023PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Capuano A, DeCorato A, Lisi L, Tringali G, Navarra P, Dello Russo C (2009) Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology. Mol Pain 5:43–55PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Ledeboer A, Tongyao L, Ahumilla JA, Mahoney JH, Vijay S, Gross MI et al (2006) The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain. Neuron Glio Biol 2:279–291CrossRefGoogle Scholar
  80. 80.
    Ledeboer A, Hutchinson MR, Watkins LR, Johnson KW (2007) Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes. Expert Opin Investig Drugs 16:935–950PubMedCrossRefGoogle Scholar
  81. 81.
    Targeting glial inhibition to attenuate chronic migraine: an international double-blind, randomised, placebo-controlled trial of ibudilast. NCT01389193. http://www.clinicaltrials.gov/ct2/show/NCT01389193. Accessed 25 Feb 2014
  82. 82.
    Ibudilast in the treatment of medication overuse headache: a double-blind, randomised, placebo-controlled pilot study. NCT01317992. http://www.clinicaltrials.gov/ct2/show/NCT01317992. Accessed 25 Feb 2014
  83. 83.
    Lipton RB, Dodick DW, Silberstein SD, Saper JR, Aurora SK, Pearlman SH et al (2010) Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham-controlled trial. Lancet Neurl 9:373–380Google Scholar
  84. 84.
    Clarke BM, Upton ARM, Kamath MV, Al-Harbi T, Castellasnos CM (2006) Transcranial magnetic stimulation for migraine: clinical effects. J Headache Pain 7:341–346PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS (2007) Occipital nerve stimulation for chronic headache—long-term safety and efficacy. Cephalalgia 27:153–157PubMedCrossRefGoogle Scholar
  86. 86.
    Matharu MS, Bartsch T, Ward N, Frackowiak RSJ, Weiner R, Goadsby PJ (2004) Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain 127:220–230PubMedCrossRefGoogle Scholar
  87. 87.
    Saper JR, Dodick DW, Silberstein SD, McCarville S, Sun M, Goadsby PJ (2011) Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia 31:271–285PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Silberstein SD, Dodick DW, Saper J, Huh B, Slavin KV, Sharan A et al (2012) Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia 32:1165–1179PubMedCrossRefGoogle Scholar
  89. 89.
    Reed KL, Black SB, Banta CJ II, Will KR (2010) Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: initial experience. Cephalalgia 30:260–271PubMedGoogle Scholar
  90. 90.
    Schoenen J, Jensen RH, Lanteri-Minet M, Lainez MJ, Gaul C, Goodman AM et al (2013) Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia 33:816–830PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Sadler RM, Purdy RA, Rahey S (2002) Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia 22:482–484PubMedCrossRefGoogle Scholar
  92. 92.
    Mauskop A (2005) Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia 25:82–86PubMedCrossRefGoogle Scholar
  93. 93.
    Hord ED, Evans MS, Mueed S, Adamolekun B, Naritoku DK (2003) The effect of vagus nerve stimulation on migraines. J Pain 4:530–534PubMedCrossRefGoogle Scholar
  94. 94.
    Lenaerts ME, Oommen KJ, Couch JR, Skaggs V (2008) Can vagus nerve stimulation help migraine? Cephalalgia 28:392–395PubMedCrossRefGoogle Scholar
  95. 95.
    Cecchini AP, Mea E, Tullo V, Curone M, Franzoni A, Broggi G et al (2009) Vagus nerve stimulation in drug-resistant daily chronic migraine with depression preliminary data. Neurol Sci 30:S101–S104PubMedCrossRefGoogle Scholar
  96. 96.
    Oshinsky ML, Murphy AL, Cooper ME, Simon BJ (2013) Trigeminal pain is suppressed by non-invasive vagal nerve stimulation in a rat headache model. J Headache Pain 1:P80CrossRefGoogle Scholar
  97. 97.
    Goadsby P (2013) Non-invasive vagus nerve stimulation (nVNS) for acute treatment of migraine: an open-label pilot study. In: American Academy of Neurology’s 65th AAN Annual Meeting. San Diego, CA, USAGoogle Scholar
  98. 98.
    Nesbitt AD, Marin JCA, Tomkins E, Ruttledge MH, Goadsby PJ (2013) Non-invasive vagus nerve stimulation for the treatment of cluster headache: a case series. J Headache Pain 1:P231CrossRefGoogle Scholar
  99. 99.
    Gerardy PY, Fabry D, Fumal A, Schoenen J (2009) A pilot study on supra-orbital surface electrotherapy in migraine. Cephalalgia 29:134Google Scholar
  100. 100.
    Schoenen J, Vandermissen B, Jeangette S, Herroelen L, Vandenheede M, Gerard P et al (2013) Migraine prevention with a supraorbital transcutaneous stimulator: a randomized controlled trial. Neurology 80:697–704PubMedCrossRefGoogle Scholar
  101. 101.
    Magis D, Salva S, D’Elia TS, Baschi R, Schoenen J (2013) Safety and patients’ satisfaction of transcutaneous supraorbital neurostimulation (tSNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population. J Headache Pain 14:95PubMedCrossRefGoogle Scholar
  102. 102.
    Vollbracht S, Rapoport AM (2013) The pipeline in headache therapy. CNS Drugs 27:717–729PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  1. 1.Department of Neurology, Montefiore Headache CenterAlbert Einstein College of MedicineBronxUSA
  2. 2.The David Geffen School of Medicine at UCLALos AngelesUSA
  3. 3.The International Headache Society PresidentLondonUnited Kingdom

Personalised recommendations