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Published in:

01-09-2013 | Review Article

The Pipeline in Headache Therapy

Authors: Sarah Vollbracht, Alan M. Rapoport

Published in: CNS Drugs | Issue 9/2013

Abstract

Migraine is a common, disabling, neurovascular disorder characterized by episodic attacks of head pain and associated disability plus systemic autonomic and neurologic symptoms. The advent of the triptan class of medication in the 1990s revolutionized the acute treatment of migraine, but many migraineurs do not respond optimally or at all to triptans, have intolerable adverse effects, or have contraindications to their use. Preventive pharmacotherapy has advanced mostly through serendipity, with new drugs being found effective while being used for other indications. There remains a significant need for new medications and devices that can provide effective, rapid, and sustained pain relief without adverse effects or recurrence. Several new acute and preventive therapies for the treatment of migraine and cluster headaches have shown promise and are currently under investigation. This article covers innovative delivery mechanisms, calcitonin gene-related peptide receptor antagonists, antibodies to calcitonin gene-related peptide and its receptor, 5-HT_1F receptor agonists, transient receptor potential vanilloid receptor modulators, orexin receptor antagonists, glial cell modulators, and neurostimulation.

Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010;30(2):107–19.PubMedCrossRef

Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT (1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668–75.PubMedCrossRef

Cambia (™) [prescribing information]. Nautilus Neurosciences, Inc.: Bedminster; 2010.

Diener H-C, Montagna P, Gàcs G, Lyczak P, Schumann G, Zoller B, et al. 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. 2006;26(5):537–47.PubMedCrossRef

Lipton RB, Grosberg B, Singer RP, Pearlman SH, Sorrentino JV, Quiring JN, et al. 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. 2010;30(11):1336–45.PubMedCrossRef

Brandes JL, Cady RK, Freitag FG, Smith TR, Chandler P, Fox AW, et al. Needle-free subcutaneous sumatriptan (Sumavel(™) DosePro(™)): bioequivalence and ease of use. Headache. 2009;48:355–67.

SUMAVEL^® DosePro^® [prescribing information]. Zogenix: San Diego; 2011.

Rothrock JF, Cady RK, Aurora SK, Brandes JL, Meyers JA, Fox AW, et al. 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. 2011;27(11):2185–91.PubMedCrossRef

Cady RK, Aurora SK, Brandes JL, Rothrock JF, Myers JA, Fox AW, et al. Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans. Headache. 2011;51:1202–11.PubMedCrossRef

10.

Patel SR, Zhong H, Sharma A, Kalia YN. In vitro and in vivo evaluation of the transdermal iontophoretic delivery of sumatriptan succinate. Eur J Pharmaceut Biopharmaceut. 2007;66:296–301.CrossRef

11.

Vikelis M, Mitsikostas D, Rapoport AM. Sumatriptan transdermal iontophoretic patch (NP101-Zelrix(™)): review of pharmacology, clinical efficacy, and safety in the acute treatment of migraine. Neuropsychiatr Dis Treat. 2012;8:429–34.PubMedCentralPubMedCrossRef

12.

Zecuity(™) [prescribing information]. Nupathe, Inc.: Conshohocken; 2013.

13.

Siegel SJ, O’Neill CO, Dube LM, Kaldeway P, Morris R, Jackson D, et al. A unique iontophoretic patch for optimal transdermal delivery of sumatriptan. Pharm Res. 2007;24(10):1919–26.PubMedCrossRef

14.

Pierce M, Marbury T, O’Neill C, Siegel S, Du W, Sebree T. Zelrix(™): a novel transdermal formulation of sumatriptan. Headache. 2009;49:817–25.PubMedCrossRef

15.

Goldstein J, Smith TR, Pugach N, Griesser M, Sebree T, Pierce M. A sumatriptan iontophoretic transdermal system for the acute treatment of migraine. Headache. 2012;52:1402–10.PubMedCrossRef

16.

Smith TR, Goldstein J, Singer R, Pugach N, Silberstein S, Pierce MW. Twelve-month tolerability and efficacy study of np101, the sumatriptan iontophoretic transdermal system. Headache. 2012;52:612–24.PubMedCrossRef

17.

Alsuma(™) [prescribing information]. Pfizer Inc.: New York; 2012.

18.

Landy SH, Tepper SJ, Wein T, Schweizer E, Ramos E. An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan. Headache. 2013;53(1):118–25.PubMedCrossRef

19.

Silberstein S. MAP0004: dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine. Expert Opin Pharmacother. 2012;13(13):1961–8.PubMedCrossRef

20.

Shrewsbury SB, Cook RO, Taylor G, Edwards C, Ramadan NM. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a novel (Tempo(™)) inhaler. Headache. 2008;48:355–67.PubMedCrossRef

21.

Aurora SK, Rozen TD, Kori SH, Shrewsbury SB. A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache. 2009;49:826–37.PubMedCrossRef

22.

Aurora SK, Silberstein SD, Kori SH, Tepper SJ, Borland SW, Wang M, et al. MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine. Headache. 2011;51:507–17.PubMedCrossRef

23.

Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004;55(1):19–26.PubMedCrossRef

24.

Burstein R, Jakubowski M. Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol. 2004;55(1):27–36.PubMedCrossRef

25.

Tepper SJ, Kori SH, Borland SW, Wang MH, Hu B, Mathew NT, et al. Efficacy and safety of MAP0004, orally inhaled DHE in treating migraine with and without allodynia. Headache. 2012;52:37–47.PubMedCrossRef

26.

Luthringer R, Djupesland PG, Sheldrake CD, Flint A, Boeijinga P, Danjou P, et al. 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. 2009;61(9):1219–28.PubMedCrossRef

27.

Djupesland PG, Docekal P, Czech Migraine Investigators Group. Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: a randomised, placebo-controlled study. Cephalalgia. 2010;30(8):933–42.PubMed

28.

Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol. 1993;33:48–56.PubMedCrossRef

29.

Tajti J, Uddman R, Moller S, Sundler F, Edvinsson L. Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst. 1999;76(2–3):176–83.PubMedCrossRef

30.

Eftekhari S, Salvatore CA, Calamari A, Kane SA, Tajti J, Edvinsson L. Differential distribution of calcitonin gene related peptide and its receptor components in the human trigeminal ganglion. Neuroscience. 2010;169(2):683–96.PubMedCrossRef

31.

Edvinsson L, Gulbenkian S, Barrosco CP, Cunha e Sá M, Polack JM, Mortensen A, et al. Innervation of the human middle meningeal artery: immunohistochemistry, ultrastructure, and role of endothelium for vasomotility. Peptides. 1998;19(7):1213–25.PubMedCrossRef

32.

Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28:183–7.PubMedCrossRef

33.

Gallai V, Sarchielli P, Floridi A, Franceschini M, Cadini M, Glioti G, et al. Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia. 1995;15:384–90.PubMedCrossRef

34.

Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol. 1988;23(2):193–6.PubMedCrossRef

35.

Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S. Increase in plasma calcitonin-gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain. 1995;60(2):119–23.PubMedCrossRef

36.

Storer RJ, Akerman S, Goadsby PJ. Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Br J Pharmacol. 2004;142(7):1171–81.PubMedCrossRef

37.

Goadsby PJ. Recent advances in understanding migraine mechanisms, molecules, and therapeutics. Trends Mol Med. 2007;13(1):39–44.PubMedCrossRef

38.

Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med. 2004;350(11):1104–10.PubMedCrossRef

39.

Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ, et al. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology. 2008;70(16):1304–12.PubMedCrossRef

40.

Hewitt DJ, Martin V, Lipton RB, Brandes J, Ceesay P, Gottwald R, et al. Randomized controlled study of telcagepant plus ibuprofen or acetominophen in migraine. Headache. 2011;51:533–43.PubMedCrossRef

41.

Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, et al. 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. 2008;372(9656):2115–23.PubMedCrossRef

42.

Connor KM, Shapiro RE, Diener HC, Lucus S, Kost J, Fan X, et al. Randomized, controlled trial of telcagepant for the acute treatment of migraine. Neurology. 2009;73(12):970–7.PubMedCrossRef

43.

Hewitt DJ, Aurora SK, Dodick DW, Goadsby PJ, Ge YJ, Bachman R, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia. 2011;31(6):712–22.PubMedCrossRef

44.

Ho TW, Ho AP, Chaitman BR, Johnson C, Mathew NT, Kost J, et al. Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease. Headache. 2012;52(2):224–35.PubMedCrossRef

45.

van der Schueren BJ, Blanchard R, Murphy MG, Palcza J, De Lepeleire I, Van Hecken A, et al. The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol. 2010;71(5):708–17.CrossRef

46.

Ho AP, Dahlof CG, Silberstein SD, Saper JR, Ashina M, Kost JT, et al. Randomized, controlled trial of telcagepant over four migraine attacks. Cephalalgia. 2010;30(12):1443–57.PubMedCrossRef

47.

Connor KM, Aurora SK, Loeys T, Ashina M, Jones C, Giezek H, et al. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial. Headache. 2011;51(1):73–84.PubMedCrossRef

48.

Ho TW, Olesen J, Dodick DW, Kost J, Lines C, Ferrari MD. Antimigraine efficacy of telcagepant based on patient’s historical triptan response. Headache. 2011;51(1):64–72.PubMedCrossRef

49.

Hoffmann J, Goadsby PJ. New agents for acute treatment of migraine: CGRP receptor antagonists, iNOS inhibitors. Curr Treat Options Neurol. 2012;14(1):50–9.PubMedCrossRef

50.

Han TH, Blanchard RL, Palcza J, McCrea JB, Laethem T, Willson K, et al. Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults. J Clin Pharmacol. 2010;50(12):1367–76.PubMedCrossRef

51.

Diener HC, Barbanti P, Dahlof C, Reuter U, Habeck J, Podhorna J. BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine: results from a phase II study. Cephalalgia. 2011;31(5):573–84.PubMedCrossRef

52.

Bigal ME, Walter S, Rapoport AM. Calcitonin gene-related peptide (CGRP) and migraine: current understanding and state of development. Headache. 2013 (in press).

53.

Neeb L, Meents J, Reuter U. 5-HT-1F receptor agonists: a new treatment option for migraine attacks? Neurotherapeutics. 2010;7:176–82.PubMedCrossRef

54.

Ferrari MD, Farkkila M, Reuter U, Pilgrim A, Davis C, Krauass M. Acute treatment of migraine with the selective 5-HT-1F receptor agonist lasmitidan—a randomised proof-of-concept trial. Cephalalgia. 2010;30:1170–8.PubMedCrossRef

55.

Fakkila M, Diener HC, Geraud G, Laniz JM, Schoenen J, Pilgrim AJ. Lasmitidan (COL-144), a selective 5HT1F agonist, is a rapid and effective oral treatment for acute migraine. J Headache Pain. 2010;11(Suppl 1):S43.

56.

Jansen-Olesen I, Mortensen A, Edvinsson L. 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. 1996;16:310–6.PubMedCrossRef

57.

Rapoport AM. The therapeutic future in headache. Neurol Sci. 2012;22(Suppl 1):S119–25.CrossRef

58.

Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, Bernstein JE. Intranasal civamide for the treatment of episodic cluster headache. Arch Neurol. 2002;59:990–4.PubMedCrossRef

59.

Civamide nasal solution for cluster headache (ECH). NCT01341548. http://clinicaltrials.gov/ct2/show/NCT01341548. Accessed 26 Feb 2013.

60.

Diamond S, Freitag F, Phillips SB, Bernstein JE, Saper JR. Intranasal civamide for the acute treatment of migraine headache. Cephalalgia. 2000;20:597–602.PubMedCrossRef

61.

Bartsch T, Levy MJ, Knight YE, Goadsby PJ. Differential modulation of nociceptive dural input to [hypcretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain. 2004;109:367–78.PubMedCrossRef

62.

Holland PR, Akerman S, Goadsby PJ. Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci. 2006;24:2825–33.PubMedCrossRef

63.

Winrow CJ, Gotter AL, Cox CD, Tannenbaum PL, Garson SL, Doran SM, et al. Pharmacololgical characterization of MK-6096—a dual orexin receptor antagonist for insomnia. Neuropharmacology. 2012;62:978–87.PubMedCrossRef

64.

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.

65.

Eftekhari S, Salvatore CA, Calamari A, Kane SA, Tajti J, Edvinsson L. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion. Neuroscience. 2010;169:683–96.PubMedCrossRef

66.

Hanani M. Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev. 2005;48(3):457–76.PubMedCrossRef

67.

Garrison CJ, Dougherty PM, Carlton SM. GFAP expression in lumbar spinal cord of naive and neuropathic rats treated with MK-801. Exp Neurol. 1994;129:237–43.PubMedCrossRef

68.

Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24(8):450–5.PubMedCrossRef

69.

Wieseler-Frank J, Maier SF, Watkins LR. Glial activation and pathological pain. Neurochem Int. 2004;45(2–3):389–95.PubMedCrossRef

70.

Takeda M, Takahashi M, Matsumoto S. Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav Rev. 2009;33(6):784–92.PubMedCrossRef

71.

Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, Freeman SE, et al. Neuron-glia signaling in trigeminal ganglion: implications for migraine pathology. Headache. 2007;47:1008–23.PubMedCentralPubMedCrossRef

72.

Capuano A, DeCorato A, Lisi L, Tringali G, Navarra P, Dello Russo C. Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology. Mol Pain. 2009;5:43–55.PubMedCentralPubMedCrossRef

73.

Kruuse C, Thomsen LL, Jacobsen TB, Olesen J. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects. J Cereb Blood Flow Metab. 2002;22(9):1124–31.PubMedCrossRef

74.

Ledeboer A, Tongyao L, Ahumilla JA, Mahoney JH, Vijay S, Gross MI, et al. The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain. Neuron Glio Biol. 2006;2:279–291.

75.

Ledeboer A, Hutchinson MR, Watkins LR, Johnson KW. Ibudilast (AV-411): a new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes. Expert Opin Investig Drugs. 2007;16(7):935–50.PubMedCrossRef

76.

Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic headache—long-term safety and efficacy. Cephalalgia. 2007;27(2):153–7.PubMedCrossRef

77.

Matharu MS, Bartsch T, Ward N, Frackowiak RSJ, Weiner R, Goadsby PJ. Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain. 2004;127(Pt 1):220–30.PubMedCrossRef

78.

Saper JR, Dodick DW, Silberstein SD, McCarville S, Sun M, Goadsby PJ. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia. 2011;31(3):271–85.PubMedCentralPubMedCrossRef

79.

Reed KL, Black SB, Banta CJ II, Will KR. Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: initial experience. Cephalalgia. 2010;30(3):260–71.PubMed

80.

Schytz HW, Barlose M, Guo S, Selb J, Caparso A, Jensen R, et al. Experimental activation of the sphenopalatine ganglion provokes cluster-like attacks in humans. Cephalalgia. 2013, 1–11 (Epub ahead of print).

81.

Tepper SJ, Rezai A, Narouze S, Steiner C, Mohajer P, Ansarinia M. Acute treatment of intractable migraine with sphenopalatine ganglion electrical stimulation. Headache. 2009;49(7):983–9.PubMedCrossRef

82.

Schoenen J, Jensen RH, Lanteri-Minet M, Lainez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;6:1–15 (Epub ahead of print).

83.

Sadler RM, Purdy RA, Rahey S. Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia. 2002;22(6):482–4.PubMedCrossRef

84.

Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005;25(2):82–6.PubMedCrossRef

85.

Hord ED, Evans MS, Mueed S, Adamolekun B, Naritoku DK. The effect of vagus nerve stimulation on migraines. J Pain. 2003;4(9):530–4.PubMedCrossRef

86.

Lenaerts ME, Oommen KJ, Couch JR, Skaggs V. Can vagus nerve stimulation help migraine? Cephalalgia. 2008;28(4):392–5.PubMedCrossRef

87.

Cecchini AP, Mea E, Tullo V, Curone M, Franzoni A, Broggi G, et al. Vagus nerve stimulation in drug-resistant daily chronic migraine with depression preliminary data. Neurol Sci. 2009;30(Suppl 1):S101–4.PubMedCrossRef

88.

Oshinsky ML, Murphy AL, Cooper ME, Simon BJ. Trigeminal pain is suppressed by non-invasive vagal nerve stimulation in a rat headache model. J Headache Pain. 2013;1(Suppl 1):P80.CrossRef

89.

Goadsby P. Non-invasive vagus nerve stimulation (nVNS) for acute treatment of migraine: an open-label pilot study. American Academy of Neurology’s 65th AAN annual meeting, San Diego.

90.

Nesbitt AD, Marin JCA, Tomkins E, Ruttledge MH, Goadsby PJ. Non-invasive vagus nerve stimulation for the treatment of cluster headache: a case series. J Headache Pain. 2013;1(Suppl 1):P231.CrossRef

91.

Gerardy PY, Fabry D, Fumal A, Schoenen J. A pilot study on supra-orbital surface electrotherapy in migraine. Cephalalgia. 2009;29:134.

92.

Schoenen J, Vandermissen B, Jeangette S, Herroelen L, Vandenheede M, Gerard P, et al. Migraine prevention with a supraorbital transcutaneous stimulator: a randomized controlled trial. Neurology. 2013;80(8):697–704.PubMedCrossRef

93.

Lipton RB, Dodick DW, Silberstein SD, Saper JR, Aurora SK, Pearlman SH, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010;9(4):373–80.PubMedCrossRef

94.

Clarke BM, Upton ARM, Kamath MV, Al-Harbi T, Castellasnos CM. Transcranial magnetic stimulation for migraine: clinical effects. J Headache Pain. 2006;7(5):341–6.PubMedCentralPubMedCrossRef

95.

Teepker M, Hotzel J, Timmesfeld N, Reis J, Mylius V, Haag A, et al. Low-frequency rTMS of the vertex in the prophylactic treatment of migraine. Cephalalgia. 2010;30(2):137–44.PubMed

96.

Bringhina F, Piazza A, Vitello G, Aloisio A, Palermo A, Daniele O, et al. rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study. J Neurol Sci. 2004;227(1):67–71.CrossRef

97.

Misra UK, Kalita J, Bhoi SK. High frequency repetitive transcranial magnetic stimulation (rTMS) is effective in migraine prophylaxis: an open labeled study. Neurol Res. 2012;34(6):547–51.PubMedCrossRef

98.

Antal A, Kriener N, Lang N, Boros K, Paulus W. Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. Cephalalgia. 2011;31(7):820–8.PubMedCrossRef

Title: The Pipeline in Headache Therapy
Authors: Sarah Vollbracht
Alan M. Rapoport
Publication date: 01-09-2013
Publisher: Springer International Publishing
Published in: CNS Drugs / Issue 9/2013
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI: https://doi.org/10.1007/s40263-013-0090-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Pipeline in Headache Therapy

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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