Skip to main content
PMC home page
The Journal of Headache and Pain logoLink to The Journal of Headache and Pain
. 2009 Oct 1;10(6):395–406. doi: 10.1007/s10194-009-0156-9

New drugs for migraine

Lars Jacob Stovner 1,2,3,✉, Erling Tronvik 1,2,3, Knut Hagen 1,2,3
PMCID: PMC3476209  PMID: 19795182

Abstract

After the triptans, a calcitonin gene-related peptide blocker (telcagepant) is the first acute medicine that has been developed primarily for treatment of acute migraine. Otherwise, the new drugs have been developed first for other purposes, like anticonvulsants, antihypertensives and antidepressants used for migraine prophylaxis. For acute attacks, a new way to administer a traditional drug like dihydroergotamine is under way, and documentation of efficacy in migraine has been gained for some commonly used painkillers and anti-inflammatory drugs, and for some herbal extracts. Based on insights into the basic pathophysiological mechanisms of the disorder, some drugs have been developed which seem promising in early phase II studies (NOS inhibitors and 5HT1F-receptor agonists). In the future, development and enhancements of existing medicines must be accompanied by increased efforts to develop truly new migraine drugs based on knowledge of the pathophysiology if one wishes to reduce substantially the great burden migraine poses on patients and society.

Keywords: Migraine, New drugs, Randomized trials, Review, Innovation

Full Text

The Full Text of this article is available as a PDF (244.2 KB).

Conflict of interest

None.

References

  • 1.Andlin-Sobocki P, Jönsson B, Wittchen HU, Olesen J. Cost of disorders of the brain in Europe. Eur J Neurol. 2005;12:1–27. doi: 10.1111/j.1468-1331.2005.01202.x. [DOI] [PubMed] [Google Scholar]
  • 2.Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, Steiner T, Zwart JA. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27:193–210. doi: 10.1111/j.1468-2982.2007.01288.x. [DOI] [PubMed] [Google Scholar]
  • 3.Steiner TJ. Lifting the burden: the global campaign to reduce the burden of headache worldwide. J Headache Pain. 2005;6:373–377. doi: 10.1007/s10194-005-0241-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Olesen J, Lekander I, Andlin-Sobocki P, Jonsson B. Funding of headache research in Europe. Cephalalgia. 2007;27:995–999. doi: 10.1111/j.1468-2982.2007.01397.x. [DOI] [PubMed] [Google Scholar]
  • 5.Burstein R. Deconstructing migraine headache into peripheral and central sensitization. Pain. 2001;89:107–110. doi: 10.1016/S0304-3959(00)00478-4. [DOI] [PubMed] [Google Scholar]
  • 6.Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol. 2006;100:1059–1064. doi: 10.1152/japplphysiol.00954.2005. [DOI] [PubMed] [Google Scholar]
  • 7.Weiller C, May A, Limmroth V, Juptner M, Kaube H, Schayck RV, Coenen HH, Diener HC. Brain stem activation in spontaneous human migraine attacks. Nat Med. 1995;1:658–660. doi: 10.1038/nm0795-658. [DOI] [PubMed] [Google Scholar]
  • 8.Panconesi A. Serotonin and migraine: a reconsideration of the central theory. J Headache Pain. 2008;9:267–276. doi: 10.1007/s10194-008-0058-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Schwedt TJ, Dodick DW. Advanced neuroimaging of migraine. Lancet Neurol. 2009;8:560–568. doi: 10.1016/S1474-4422(09)70107-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Lauritzen M, Kraig RP (2005) Spreading depression. In: The headaches, 3rd edn. In: Olesen JG, Ramadan PJ, Tfelt-Hansen NM, Welch P (eds) K M A. Williams & Wilkins, Lippincott, pp 269–274
  • 11.Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD. Migraine: gene mutations and functional consequences. Curr Opin Neurol. 2007;20:299–305. doi: 10.1097/WCO.0b013e3281338d1f. [DOI] [PubMed] [Google Scholar]
  • 12.Dahlöf C. Integrating the triptans into clinical practice. Curr Opin Neurol. 2002;15:317–322. doi: 10.1097/00019052-200206000-00015. [DOI] [PubMed] [Google Scholar]
  • 13.Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia. 2002;22:633–658. doi: 10.1046/j.1468-2982.2002.00404.x. [DOI] [PubMed] [Google Scholar]
  • 14.Mathew NT. Antiepileptic drugs in migraine prevention. Headache. 2001;41(Suppl 1):S18–S24. doi: 10.1046/j.1526-4610.2001.01154-4.x. [DOI] [PubMed] [Google Scholar]
  • 15.Mulleners WM, Chronicle EP. Anticonvulsants in migraine prophylaxis: a Cochrane review. Cephalalgia. 2008;28:585–597. doi: 10.1111/j.1468-2982.2008.01571.x. [DOI] [PubMed] [Google Scholar]
  • 16.Bakola E, Skapinakis P, Tzoufi M, Damigos D, Mavreas V (2008) Anticonvulsant drugs for pediatric migraine prevention: an evidence-based review. Eur J Pain [DOI] [PubMed]
  • 17.Casucci G, Villani V, Frediani F. Central mechanism of action of antimigraine prophylactic drugs. Neurol Sci. 2008;29(Suppl 1):S123–S126. doi: 10.1007/s10072-008-0902-9. [DOI] [PubMed] [Google Scholar]
  • 18.Martella G, Costa C, Pisani A, Cupini LM, Bernardi G, Calabresi P. Antiepileptic drugs on calcium currents recorded from cortical and PAG neurons: therapeutic implications for migraine. Cephalalgia. 2008;28:1315–1326. doi: 10.1111/j.1468-2982.2008.01682.x. [DOI] [PubMed] [Google Scholar]
  • 19.Storey JR, Calder CS, Hart DE, Potter DL. Topiramate in migraine prevention: a double-blind, placebo-controlled study. Headache. 2001;41:968–975. doi: 10.1046/j.1526-4610.2001.01190.x. [DOI] [PubMed] [Google Scholar]
  • 20.Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L. Topiramate in the treatment of chronic migraine. Cephalalgia. 2003;23:820–824. doi: 10.1046/j.1468-2982.2003.00592.x. [DOI] [PubMed] [Google Scholar]
  • 21.Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291:965–973. doi: 10.1001/jama.291.8.965. [DOI] [PubMed] [Google Scholar]
  • 22.Diener HC, Tfelt-Hansen P, Dahlof C, Lainez MJ, Sandrini G, Wang SJ, Neto W, Vijapurkar U, Doyle A, Jacobs D. Topiramate in migraine prophylaxis—results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943–950. doi: 10.1007/s00415-004-0464-6. [DOI] [PubMed] [Google Scholar]
  • 23.Silberstein SD, Neto W, Schmitt J, Jacobs D. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–495. doi: 10.1001/archneur.61.4.490. [DOI] [PubMed] [Google Scholar]
  • 24.Silberstein SD, Hulihan J, Karim MR, Wu SC, Jordan D, Karvois D, Kamin M. Efficacy and tolerability of topiramate 200 mg/d in the prevention of migraine with/without aura in adults: a randomized, placebo-controlled, double-blind, 12-week pilot study. Clin Ther. 2006;28:1002–1011. doi: 10.1016/j.clinthera.2006.07.003. [DOI] [PubMed] [Google Scholar]
  • 25.Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes JL, Bigal M, Saper J, Ascher S, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47:170–180. doi: 10.1111/j.1526-4610.2006.00684.x. [DOI] [PubMed] [Google Scholar]
  • 26.Diener HC, Bussone G, Oene JC, Lahaye M, Schwalen S, Goadsby PJ. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27:814–823. doi: 10.1111/j.1468-2982.2007.01326.x. [DOI] [PubMed] [Google Scholar]
  • 27.Keskinbora K, Aydinli I. A double-blind randomized controlled trial of topiramate and amitriptyline either alone or in combination for the prevention of migraine. Clin Neurol Neurosurg. 2008;110:979–984. doi: 10.1016/j.clineuro.2008.05.025. [DOI] [PubMed] [Google Scholar]
  • 28.Ashtari F, Shaygannejad V, Akbari M. A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis. Acta Neurol Scand. 2008;118:301–305. doi: 10.1111/j.1600-0404.2008.01087.x. [DOI] [PubMed] [Google Scholar]
  • 29.Millan-Guerrero RO, Isais-Millan R, Barreto-Vizcaino S, Gutierrez I, Rivera-Castano L, Trujillo-Hernandez B, Baltazar LM. Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study. Eur Neurol. 2008;59:237–242. doi: 10.1159/000115637. [DOI] [PubMed] [Google Scholar]
  • 30.Dodick DW, Freitag F, Banks J, Saper J, Xiang J, Rupnow M, Biondi D, Greenberg SJ, Hulihan J. Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs. Clin Ther. 2009;31:542–559. doi: 10.1016/j.clinthera.2009.03.020. [DOI] [PubMed] [Google Scholar]
  • 31.Adelman J, Freitag FG, Lainez M, Shi Y, Ascher S, Mao L, Greenberg S, Hulihan J. Analysis of safety and tolerability data obtained from over 1,500 patients receiving topiramate for migraine prevention in controlled trials. Pain Med. 2008;9:175–185. doi: 10.1111/j.1526-4637.2007.00389.x. [DOI] [PubMed] [Google Scholar]
  • 32.White HS. Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache. 2005;45(Suppl 1):S48–S56. doi: 10.1111/j.1526-4610.2005.4501006.x. [DOI] [PubMed] [Google Scholar]
  • 33.Calabresi P, Galletti F, Rossi C, Sarchielli P, Cupini LM. Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms. Trends Pharmacol Sci. 2007;28:188–195. doi: 10.1016/j.tips.2007.02.005. [DOI] [PubMed] [Google Scholar]
  • 34.Azimova YE, Tabeeva GR. Prophylactic treatment of migraine with topamax: long-term results. Neurosci Behav Physiol. 2007;37:125–127. doi: 10.1007/s11055-007-0159-4. [DOI] [PubMed] [Google Scholar]
  • 35.Artemenko AR, Kurenkov AL, Filatova EG, Nikitin SS, Kaube H, Katsarava Z. Effects of topiramate on migraine frequency and cortical excitability in patients with frequent migraine. Cephalalgia. 2008;28:203–208. doi: 10.1111/j.1468-2982.2007.01491.x. [DOI] [PubMed] [Google Scholar]
  • 36.D’Amico D, Grazzi L, Bussone G. Topiramate in the prevention of migraine: a review of its efficacy, tolerability, and acceptability. Neuropsychiatr Dis Treat. 2006;2:261–267. doi: 10.2147/nedt.2006.2.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Di Trapani G, Mei D, Marra C, Mazza S, Capuano A. Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study. Clin Ther. 2000;151:145–148. [PubMed] [Google Scholar]
  • 38.Mathew NT, Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, Stacey B, Tepper S. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41:119–128. doi: 10.1046/j.1526-4610.2001.111006119.x. [DOI] [PubMed] [Google Scholar]
  • 39.Jimenez-Hernandez MD, Torrecillas Narvaez MD, Friera Acebal G. Effectiveness and safety of gabapentin in the preventive treatment of migraine. Rev Neurol. 2002;35:603–606. [PubMed] [Google Scholar]
  • 40.Steiner TJ, Findley LJ, Yuen AW. Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia. 1997;17:109–112. doi: 10.1046/j.1468-2982.1997.1702109.x. [DOI] [PubMed] [Google Scholar]
  • 41.Pascual J, Caminero AB, Mateos V, Roig C, Leira R, Garcia-Monco C, Lainez MJ. Preventing disturbing migraine aura with lamotrigine: an open study. Headache. 2004;44:1024–1028. doi: 10.1111/j.1526-4610.2004.04198.x. [DOI] [PubMed] [Google Scholar]
  • 42.Lampl C, Katsarava Z, Diener HC, Limmroth V. Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. J Neurol Neurosurg Psychiatry. 2005;76:1730–1732. doi: 10.1136/jnnp.2005.063750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.d’Onofrio F, Cologno D, Petretta V, Casucci G, Bussone G. Basilar-type migraine responsive to lamotrigine: three case reports. Neurol Sci. 2007;28(Suppl 2):S239–S241. doi: 10.1007/s10072-007-0787-z. [DOI] [PubMed] [Google Scholar]
  • 44.Silberstein S, Saper J, Berenson F, Somogyi M, McCague K, D’Souza J. Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study. Neurology. 2008;70:548–555. doi: 10.1212/01.wnl.0000297551.27191.70. [DOI] [PubMed] [Google Scholar]
  • 45.Drake ME, Jr, Greathouse NI, Renner JB, Armentbright AD. Open-label zonisamide for refractory migraine. Clin Neuropharmacol. 2004;27:278–280. doi: 10.1097/01.wnf.0000150866.98887.77. [DOI] [PubMed] [Google Scholar]
  • 46.Ashkenazi A, Benlifer A, Korenblit J, Silberstein SD. Zonisamide for migraine prophylaxis in refractory patients. Cephalalgia. 2006;26:1199–1202. doi: 10.1111/j.1468-2982.2006.01191.x. [DOI] [PubMed] [Google Scholar]
  • 47.Bermejo PE, Dorado R (2009) Zonisamide for migraine prophylaxis in patients refractory to topiramate. Clin Neuropharmacol 32(2):103–106 [DOI] [PubMed]
  • 48.Pakalnis A, Kring D. Zonisamide prophylaxis in refractory pediatric headache. Headache. 2006;46:804–807. doi: 10.1111/j.1526-4610.2006.00455.x. [DOI] [PubMed] [Google Scholar]
  • 49.Miller GS. Efficacy and safety of levetiracetam in pediatric migraine. Headache. 2004;44:238–243. doi: 10.1111/j.1526-4610.2004.04053.x. [DOI] [PubMed] [Google Scholar]
  • 50.Pakalnis A, Kring D, Meier L. Levetiracetam prophylaxis in pediatric migraine—an open-label study. Headache. 2007;47:427–430. doi: 10.1111/j.1526-4610.2007.00728.x. [DOI] [PubMed] [Google Scholar]
  • 51.Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B. Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study. Clin Neuropharmacol. 2006;29:338–342. doi: 10.1097/01.WNF.0000236766.08409.03. [DOI] [PubMed] [Google Scholar]
  • 52.Read SJ, Hirst WD, Upton N, Parsons AA. Cortical spreading depression produces increased cGMP levels in cortex and brain stem that is inhibited by tonabersat (SB-220453) but not sumatriptan. Brain Res. 2001;891:69–77. doi: 10.1016/S0006-8993(00)03191-7. [DOI] [PubMed] [Google Scholar]
  • 53.Read SJ, Smith MI, Hunter AJ, Upton N, Parsons AA. SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release following induction of cortical spreading depression in the anaesthetized cat. Cephalalgia. 2000;20:92–99. doi: 10.1046/j.1468-2982.2000.00022.x. [DOI] [PubMed] [Google Scholar]
  • 54.MaassenVanDenBrink A, Broek RW, Vries R, Upton N, Parsons AA, Saxena PR. The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan. Cephalalgia. 2000;20:538–545. doi: 10.1046/j.1468-2982.2000.00078.x. [DOI] [PubMed] [Google Scholar]
  • 55.Parsons AA, Bingham S, Raval P, Read S, Thompson M, Upton N. Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes. Br J Pharmacol. 2001;132:1549–1557. doi: 10.1038/sj.bjp.0703932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Tvedskov JF, Iversen HK, Olesen J. A double-blind study of SB-220453 (Tonerbasat) in the glyceryltrinitrate (GTN) model of migraine. Cephalalgia. 2004;24:875–882. doi: 10.1111/j.1468-2982.2004.00762.x. [DOI] [PubMed] [Google Scholar]
  • 57.Goadsby PJ, Ferrari MD, Csanyi A, Olesen J, Mills JG. Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Cephalalgia. 2009;29:742–750. doi: 10.1111/j.1468-2982.2008.01804.x. [DOI] [PubMed] [Google Scholar]
  • 58.Hauge AW, Asghar MS, Schytz HW, Christensen K, Olesen J. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet Neurol. 2009;8:718–723. doi: 10.1016/S1474-4422(09)70135-8. [DOI] [PubMed] [Google Scholar]
  • 59.Dessy C, Saliez J, Ghisdal P, Daneau G, Lobysheva II, Frerart F, Belge C, Jnaoui K, Noirhomme P, Feron O, et al. Endothelial beta3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation beta-blocker nebivolol. Circulation. 2005;112:1198–1205. doi: 10.1161/CIRCULATIONAHA.104.532960. [DOI] [PubMed] [Google Scholar]
  • 60.Schellenberg R, Lichtenthal A, Wohling H, Graf C, Brixius K. Nebivolol and metoprolol for treating migraine: an advance on beta-blocker treatment? Headache. 2008;48:118–125. doi: 10.1111/j.1526-4610.2007.00785.x. [DOI] [PubMed] [Google Scholar]
  • 61.Schrader H, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ (Clinical researched) 2001;322:19–22. doi: 10.1136/bmj.322.7277.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289:65–69. doi: 10.1001/jama.289.1.65. [DOI] [PubMed] [Google Scholar]
  • 63.Diener HC, Gendolla A, Feuersenger A, Evers S, Straube A, Schumacher H et al (2009) Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial. Cephalalgia 29(9):921–927 [DOI] [PubMed]
  • 64.Stark RJ, Stark CD. Migraine prophylaxis. Med J Aust. 2008;189:283–288. doi: 10.5694/j.1326-5377.2008.tb02028.x. [DOI] [PubMed] [Google Scholar]
  • 65.Sicuteri F. Enkephalinase inhibition relieves pain syndromes of central dysnociception (migraine and related headache) Cephalalgia. 1981;1:229–232. doi: 10.1046/j.1468-2982.1981.0104229.x. [DOI] [PubMed] [Google Scholar]
  • 66.Bender WI. ACE inhibitors for prophylaxis of migraine headaches. Headache. 1995;35:470–471. doi: 10.1111/j.1526-4610.1995.hed3508470.x. [DOI] [PubMed] [Google Scholar]
  • 67.Schuh-Hofer S, Flach U, Meisel A, Israel H, Reuter U, Arnold G. Efficacy of lisinopril in migraine prophylaxis—an open label study. Eur J Neurol. 2007;14:701–703. doi: 10.1111/j.1468-1331.2007.01764.x. [DOI] [PubMed] [Google Scholar]
  • 68.Owada K. Efficacy of candesartan in the treatment of migraine in hypertensive patients. Hypertens Res. 2004;27:441–446. doi: 10.1291/hypres.27.441. [DOI] [PubMed] [Google Scholar]
  • 69.Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC. Reduction in the therapeutic intensity of abortive migraine drug use during ACE inhibition therapy—a pilot study. Pharmacoepidemiol Drug Saf. 2004;13:41–47. doi: 10.1002/pds.893. [DOI] [PubMed] [Google Scholar]
  • 70.Etminan M, Levine MA, Tomlinson G, Rochon PA. Efficacy of angiotensin II receptor antagonists in preventing headache: a systematic overview and meta-analysis. Am J Med. 2002;112:642–646. doi: 10.1016/S0002-9343(02)01100-2. [DOI] [PubMed] [Google Scholar]
  • 71.Saavedra JM, Benicky J, Zhou J. Angiotensin II: multitasking in the brain. J Hypertens Suppl. 2006;24:S131–S137. doi: 10.1097/01.hjh.0000220418.09021.ee. [DOI] [PubMed] [Google Scholar]
  • 72.Imboden H, Patil J, Nussberger J, Nicoud F, Hess B, Ahmed N, Schaffner T, Wellner M, Muller D, Inagami T, et al. Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia. Regul Pept. 2009;154:23–31. doi: 10.1016/j.regpep.2009.02.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Ramadan NM, Schultz LL, Gilkey SJ. Migraine prophylactic drugs: proof of efficacy, utilization and cost. Cephalalgia. 1997;17:73–80. doi: 10.1046/j.1468-2982.1997.1702073.x. [DOI] [PubMed] [Google Scholar]
  • 74.Moja PL, Cusi C, Sterzi RR, Canepari C (2005) Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches. Cochrane Database Syst Rev 20:CD002919 [DOI] [PubMed]
  • 75.Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R. The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005;45:144–152. doi: 10.1111/j.1526-4610.2005.05029.x. [DOI] [PubMed] [Google Scholar]
  • 76.Taylor AP, Adelman JU, Freeman MC. Efficacy of duloxetine as a migraine preventive medication: possible predictors of response in a retrospective chart review. Headache. 2007;47:1200–1203. doi: 10.1111/j.1526-4610.2007.00886.x. [DOI] [PubMed] [Google Scholar]
  • 77.Dahlof CG, Hargreaves RJ. Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies? Cephalalgia. 1998;18:593–604. doi: 10.1046/j.1468-2982.1998.1809593.x. [DOI] [PubMed] [Google Scholar]
  • 78.Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache. 2006;46:781–787. doi: 10.1111/j.1526-4610.2006.00438.x. [DOI] [PubMed] [Google Scholar]
  • 79.Bigal ME, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med. 2002;23:141–148. doi: 10.1016/S0736-4679(02)00502-4. [DOI] [PubMed] [Google Scholar]
  • 80.Silberstein SD, Young WB, Mendizabal JE, Rothrock JF, Alam AS. Acute migraine treatment with droperidol: a randomized, double-blind, placebo-controlled trial. Neurology. 2003;60:315–321. doi: 10.1212/01.wnl.0000042477.63516.b2. [DOI] [PubMed] [Google Scholar]
  • 81.Silberstein SD, Peres MF, Hopkins MM, Shechter AL, Young WB, Rozen TD. Olanzapine in the treatment of refractory migraine and chronic daily headache. Headache. 2002;42:515–518. doi: 10.1046/j.1526-4610.2002.02126.x. [DOI] [PubMed] [Google Scholar]
  • 82.Edvinsson L. CGRP-receptor antagonism in migraine treatment. Lancet. 2008;372:2089–2090. doi: 10.1016/S0140-6736(08)61710-9. [DOI] [PubMed] [Google Scholar]
  • 83.Tvedskov JF, Lipka K, Ashina M, Iversen HK, Schifter S, Olesen J. No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol. 2005;58:561–568. doi: 10.1002/ana.20605. [DOI] [PubMed] [Google Scholar]
  • 84.Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia. 2002;22:54–61. doi: 10.1046/j.1468-2982.2002.00310.x. [DOI] [PubMed] [Google Scholar]
  • 85.Link AS, Kuris A, Edvinsson L. Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J Headache Pain. 2008;9:5–12. doi: 10.1007/s10194-008-0011-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med. 2004;350:1104–1110. doi: 10.1056/NEJMoa030505. [DOI] [PubMed] [Google Scholar]
  • 87.Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, 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 randomised, placebo-controlled, parallel-treatment trial. Lancet. 2008;372:2115–2123. doi: 10.1016/S0140-6736(08)61626-8. [DOI] [PubMed] [Google Scholar]
  • 88.Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ, Lines CR, Rapoport AM. Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology. 2008;70:1304–1312. doi: 10.1212/01.WNL.0000286940.29755.61. [DOI] [PubMed] [Google Scholar]
  • 89.Juhl L, Edvinsson L, Olesen J, Jansen-Olesen I. Effect of two novel CGRP-binding compounds in a closed cranial window rat model. Eur J Pharmacol. 2007;567:117–124. doi: 10.1016/j.ejphar.2007.04.004. [DOI] [PubMed] [Google Scholar]
  • 90.Levy MJ, Matharu MS, Bhola R, Meeran K, Goadsby PJ. Octreotide is not effective in the acute treatment of migraine. Cephalalgia. 2005;25:48–55. doi: 10.1111/j.1468-2982.2004.00807.x. [DOI] [PubMed] [Google Scholar]
  • 91.Olesen J. The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache. Pharmacol Ther. 2008;120:157–171. doi: 10.1016/j.pharmthera.2008.08.003. [DOI] [PubMed] [Google Scholar]
  • 92.Lassen LH, Ashina M, Christiansen I, Ulrich V, Grover R, Donaldson J, Olesen J. Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks. Cephalalgia. 1998;18:27–32. doi: 10.1046/j.1468-2982.1998.1801027.x. [DOI] [PubMed] [Google Scholar]
  • 93.Kuy PH, Merkus FW, Lohman JJ, ter Berg JW, Hooymans PM. Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study. Cephalalgia. 2002;22:513–519. doi: 10.1046/j.1468-2982.2002.00412.x. [DOI] [PubMed] [Google Scholar]
  • 94.McCall RB, Huff R, Chio CL, TenBrink R, Bergh CL, Ennis MD, Ghazal NB, Hoffman RL, Meisheri K, Higdon NR, et al. Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633. Cephalalgia. 2002;22:799–806. doi: 10.1046/j.1468-2982.2002.00459.x. [DOI] [PubMed] [Google Scholar]
  • 95.Gomez-Mancilla B, Cutler NR, Leibowitz MT, Spierings EL, Klapper JA, Diamond S, Goldstein J, Smith T, Couch JR, Fleishaker J, et al. Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with acute migraine. Cephalalgia. 2001;21:727–732. doi: 10.1046/j.1468-2982.2001.00208.x. [DOI] [PubMed] [Google Scholar]
  • 96.Goldstein DJ, Roon KI, Offen WW, Ramadan NM, Phebus LA, Johnson KW, Schaus JM, Ferrari MD. Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial. Lancet. 2001;358:1230–1234. doi: 10.1016/S0140-6736(01)06347-4. [DOI] [PubMed] [Google Scholar]
  • 97.Ramadan NM, Skljarevski V, Phebus LA, Johnson KW. 5-HT1F receptor agonists in acute migraine treatment: a hypothesis. Cephalalgia. 2003;23:776–785. doi: 10.1046/j.1468-2982.2003.00525.x. [DOI] [PubMed] [Google Scholar]
  • 98.Saper JR, Silberstein S, Dodick D, Rapoport A. DHE in the pharmacotherapy of migraine: potential for a larger role. Headache. 2006;46(Suppl 4):S212–S220. doi: 10.1111/j.1526-4610.2006.00605.x. [DOI] [PubMed] [Google Scholar]
  • 99.Shrewsbury SB, Cook RO, Taylor G, Edwards C, Ramadan NM. Safety and pharmacokinetics of dihydroergotamine mesylate administered via a Novel (Tempo) inhaler. Headache. 2008;48:355–367. doi: 10.1111/j.1526-4610.2007.01006.x. [DOI] [PubMed] [Google Scholar]
  • 100.Shrewsbury SB, Kori SH, Miller SD, Pedinoff A, Weinstein S. Randomized, double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of MAP0004 (orally-inhaled DHE) in adult asthmatics. Curr Med Res Opin. 2008;24:1977–1985. doi: 10.1185/03007990802160677. [DOI] [PubMed] [Google Scholar]
  • 101.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(6):826–837 [DOI] [PubMed]
  • 102.Kaube H, Herzog J, Kaufer T, Dichgans M, Diener HC. Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine. Neurology. 2000;55:139–141. doi: 10.1212/wnl.55.1.139. [DOI] [PubMed] [Google Scholar]
  • 103.Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein SD, Johnson KW, Phebus LA, Bleakman D, et al. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia. 2004;24:596–602. doi: 10.1111/j.1468-2982.2004.00723.x. [DOI] [PubMed] [Google Scholar]
  • 104.Szallasi A, Cortright DN, Blum CA, Eid SR. The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov. 2007;6:357–372. doi: 10.1038/nrd2280. [DOI] [PubMed] [Google Scholar]
  • 105.Knotkova H, Pappagallo M, Szallasi A. Capsaicin (TRPV1 Agonist) therapy for pain relief: farewell or revival? Clin J Pain. 2008;24:142–154. doi: 10.1097/AJP.0b013e318158ed9e. [DOI] [PubMed] [Google Scholar]
  • 106.Funk CD, FitzGerald GA. COX-2 inhibitors and cardiovascular risk. J Cardiovasc Pharmacol. 2007;50:470–479. doi: 10.1097/FJC.0b013e318157f72d. [DOI] [PubMed] [Google Scholar]
  • 107.Silberstein S, Tepper S, Brandes J, Diamond M, Goldstein J, Winner P, Venkatraman S, Vrijens F, Malbecq W, Lines C, et al. Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine. Neurology. 2004;62:1552–1557. doi: 10.1212/01.wnl.0000123260.61631.c4. [DOI] [PubMed] [Google Scholar]
  • 108.Kudrow D, Thomas HM, Ruoff G, Ishkanian G, Sands G, Le VH, Brown MT. Valdecoxib for treatment of a single, acute, moderate to severe migraine headache. Headache. 2005;45:1151–1162. doi: 10.1111/j.1526-4610.2005.00238.x. [DOI] [PubMed] [Google Scholar]
  • 109.Loo CY, Tan HJ, Teh HS, Raymond AA. Randomised, open label, controlled trial of celecoxib in the treatment of acute migraine. Singapore Med J. 2007;48:834–839. [PubMed] [Google Scholar]
  • 110.Vecsei L, Gallacchi G, Sagi I, Semjen J, Tajti J, Szok D, Muller M, Vadass P, Kerekgyarto M. Diclofenac epolamine is effective in the treatment of acute migraine attacks. A randomized, crossover, double blind, placebo-controlled, clinical study. Cephalalgia. 2007;27:29–34. doi: 10.1111/j.1468-2982.2007.01236.x. [DOI] [PubMed] [Google Scholar]
  • 111.Peroutka SJ, Lyon JA, Swarbrick J, Lipton RB, Kolodner K, Goldstein J. Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study. Headache. 2004;44:136–141. doi: 10.1111/j.1526-4610.2004.04029.x. [DOI] [PubMed] [Google Scholar]
  • 112.Maubach KA, Davis RJ, Clark DE, Fenton G, Lockey PM, Clark KL et al (2009) BGC20-1531, a novel, potent and selective prostanoid EP receptor antagonist: a putative new treatment for migraine headache. Br J Pharmacol 156(2):316–327 [DOI] [PMC free article] [PubMed]
  • 113.Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther. 2006;319:1096–1103. doi: 10.1124/jpet.106.105569. [DOI] [PubMed] [Google Scholar]
  • 114.Nakao K, Murase A, Ohshiro H, Okumura T, Taniguchi K, Murata Y, Masuda M, Kato T, Okumura Y, Takada J. CJ-023, 423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties. J Pharmacol Exp Ther. 2007;322:686–694. doi: 10.1124/jpet.107.122010. [DOI] [PubMed] [Google Scholar]
  • 115.Couch JR, Zagami AS (2005) Status migrainosus. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA (eds) The headaches, 3rd edn. Williams & Wilkins, Lippincott, pp 595–598
  • 116.Colman I, Friedman BW, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008;336:1359–1361. doi: 10.1136/bmj.39566.806725.BE. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 117.Friedman BW, Greenwald P, Bania TC, Esses D, Hochberg M, Solorzano C, Corbo J, Chu J, Chew E, Cheung P, et al. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology. 2007;69:2038–2044. doi: 10.1212/01.WNL.0000281105.78936.1d. [DOI] [PubMed] [Google Scholar]
  • 118.Kelly AM. Migraine: pharmacotherapy in the emergency department. West J Med. 2000;173:189–193. doi: 10.1136/ewjm.173.3.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 119.Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M. Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Arch Intern Med. 2000;160:3486–3492. doi: 10.1001/archinte.160.22.3486. [DOI] [PubMed] [Google Scholar]
  • 120.Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH. Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention—a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia. 2005;25:1031–1041. doi: 10.1111/j.1468-2982.2005.00950.x. [DOI] [PubMed] [Google Scholar]
  • 121.Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51:89–97. doi: 10.1159/000076535. [DOI] [PubMed] [Google Scholar]
  • 122.Lipton RB, Gobel H, Einhaupl KM, Wilks K, Mauskop A. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240–2244. doi: 10.1212/01.wnl.0000147290.68260.11. [DOI] [PubMed] [Google Scholar]
  • 123.Gupta VK. Botulinum toxin—a treatment for migraine? A systematic review. Pain Med. 2006;7:386–394. doi: 10.1111/j.1526-4637.2006.00216.x. [DOI] [PubMed] [Google Scholar]
  • 124.Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache. 2000;40:445–450. doi: 10.1046/j.1526-4610.2000.00066.x. [DOI] [PubMed] [Google Scholar]
  • 125.Evers S, Vollmer-Haase J, Schwaag S, Rahmann A, Husstedt IW, Frese A. Botulinum toxin A in the prophylactic treatment of migraine–a randomized, double-blind, placebo-controlled study. Cephalalgia. 2004;24:838–843. doi: 10.1111/j.1468-2982.2004.00754.x. [DOI] [PubMed] [Google Scholar]
  • 126.Aurora SK, Gawel M, Brandes JL, Pokta S, Vandenburgh AM. Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study. Headache. 2007;47:486–499. doi: 10.1111/j.1526-4610.2007.00853.x. [DOI] [PubMed] [Google Scholar]
  • 127.Elkind AH, O’Carroll P, Blumenfeld A, DeGryse R, Dimitrova R. A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis. J Pain. 2006;7:688–696. doi: 10.1016/j.jpain.2006.03.002. [DOI] [PubMed] [Google Scholar]
  • 128.Relja M, Poole AC, Schoenen J, Pascual J, Lei X, Thompson C. A multicentre, double-blind, randomized, placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of episodic migraine headaches. Cephalalgia. 2007;27:492–503. doi: 10.1111/j.1468-2982.2007.01315.x. [DOI] [PubMed] [Google Scholar]
  • 129.Cady R, Schreiber C. Botulinum toxin type A as migraine preventive treatment in patients previously failing oral prophylactic treatment due to compliance issues. Headache. 2008;48:900–913. doi: 10.1111/j.1526-4610.2007.00953.x. [DOI] [PubMed] [Google Scholar]
  • 130.Evers S. Status on the use of botulinum toxin for headache disorders. Curr Opin Neurol. 2006;19:310–315. doi: 10.1097/01.wco.0000227044.08447.c3. [DOI] [PubMed] [Google Scholar]
  • 131.Schulte-Mattler WJ, Leinisch E. Evidence based medicine on the use of botulinum toxin for headache disorders. J Neural Transm. 2008;115:647–651. doi: 10.1007/s00702-007-0832-3. [DOI] [PubMed] [Google Scholar]
  • 132.Naumann M, So Y, Argoff CE, Childers MK, Dykstra DD, Gronseth GS, Jabbari B, Kaufmann HC, Schurch B, Silberstein SD, et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1707–1714. doi: 10.1212/01.wnl.0000311390.87642.d8. [DOI] [PubMed] [Google Scholar]
  • 133.Mauskop A, Mathew N. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the therapeutics and technology assessment subcommittee of the american academy of neurology. Neurology. 2009;72:1367. doi: 10.1212/WNL.0b013e3181a53375. [DOI] [PubMed] [Google Scholar]
  • 134.Smith TR, Sunshine A, Stark SR, Littlefield DE, Spruill SE, Alexander WJ. Sumatriptan and naproxen sodium for the acute treatment of migraine. Headache. 2005;45:983–991. doi: 10.1111/j.1526-4610.2005.05178.x. [DOI] [PubMed] [Google Scholar]
  • 135.Brandes JL, Kudrow D, Stark SR, O’Carroll CP, Adelman JU, O’Donnell FJ, Alexander WJ, Spruill SE, Barrett PS, Lener SE. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297:1443–1454. doi: 10.1001/jama.297.13.1443. [DOI] [PubMed] [Google Scholar]
  • 136.Winner P, Cady RK, Ruoff GE, Frishberg BM, Alexander WJ, Zhang Y, Kori SH, Lener SE. Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine. Mayo Clin Proc. 2007;82:61–68. doi: 10.4065/82.1.61. [DOI] [PubMed] [Google Scholar]
  • 137.Di Monda V, Nicolodi M, Aloisio A, Del Bianco P, Fonzari M, Grazioli I, Uslenghi C, Vecchiet L, Sicuteri F. Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial. Headache. 2003;43:835–844. doi: 10.1046/j.1526-4610.2003.03161.x. [DOI] [PubMed] [Google Scholar]
  • 138.Sandrini G, Cerbo R, Del Bene E, Ferrari A, Genco S, Grazioli I, Martelletti P, Nappi G, Pinessi L, Sarchielli P, et al. Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study. Int J Clin Pract. 2007;61:1256–1269. doi: 10.1111/j.1742-1241.2007.01458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 139.Goldstein J, Silberstein SD, Saper JR, Elkind AH, Smith TR, Gallagher RM, Battikha JP, Hoffman H, Baggish J. Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial. Headache. 2005;45:973–982. doi: 10.1111/j.1526-4610.2005.05177.x. [DOI] [PubMed] [Google Scholar]
  • 140.Silberstein SD, Freitag FG, Rozen TD, Kudrow DB, Hewitt DJ, Jordan DM, Fisher AC, Rosenthal NR. Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial. Headache. 2005;45:1317–1327. doi: 10.1111/j.1526-4610.2005.00250.x. [DOI] [PubMed] [Google Scholar]
  • 141.Maizels M, Blumenfeld A, Burchette R. A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache. 2004;44:885–890. doi: 10.1111/j.1526-4610.2004.04170.x. [DOI] [PubMed] [Google Scholar]
  • 142.Diener HC, Agosti R, Allais G, Bergmans P, Bussone G, Davies B, Ertas M, Lanteri-Minet M, Reuter U, Del Rio MS, et al. Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2007;6:1054–1062. doi: 10.1016/S1474-4422(07)70272-7. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Headache and Pain are provided here courtesy of BMC

RESOURCES