Drugs

, Volume 72, Issue 6, pp 825–845

OnabotulinumtoxinA (BOTOX®)

A Review of its Use in the Prophylaxis of Headaches in Adults with Chronic Migraine
Adis Drug Evaluation

Abstract

This article reviews the pharmacology, therapeutic efficacy and tolerability profile of intramuscularly injected onabotulinumtoxinA (onaBoNTA; BOTOX®) for headache prophylaxis in adults with chronic migraine, with a focus on UK labelling for the drug. The pharmacological actions of onaBoNTA include a direct antinociceptive (analgesic) effect; while not fully understood, the mechanism of action underlying its headache prophylaxis effect in chronic migraine is presumed to involve inhibition of peripheral and central sensitization in trigemino-vascular neurones.

Pooled findings from two large phase III studies of virtually identical design (PREEMPT [Phase III REsearch Evaluating Migraine Prophylaxis Therapy] 1 and 2) showed that treatment with up to five cycles of onaBoNTA (155–195 units/cycle) at 12-week intervals was effective in reducing headache symptoms, decreasing headache-related disability, and improving health-related quality of life (HR-QOL) in patients with chronic migraine, approximately two-thirds of whom were overusing acute headache medications at baseline. During the double-blind phase of both trials, significantly more patients treated with onaBoNTA (two cycles) than placebo experienced clinically meaningful improvements in the monthly frequencies of headache days, moderate to severe headache days and migraine days, and in the cumulative hours of headache on headache days/month. OnaBoNTA therapy also resulted in statistically significant and clinically meaningful improvements in functioning and HR-QOL compared with placebo. Notably, improvements in headache symptoms, functioning and HR-QOL favouring onaBoNTA over placebo were seen regardless of whether or not patients were medication overusers and irrespective of whether or not they were naive to (oral) prophylactic therapy. Further improvements relative to baseline in headache symptoms, functioning and HR-QOL were observed during the open-label extension phase of both trials (all patients received three cycles of onaBoNTA).

Treatment with up to five cycles of onaBoNTA was generally well tolerated in the PREEMPT trials. Treatment-related adverse events reported by onaBoNTA recipients (e.g. neck pain, facial paresis and eyelid ptosis) were consistent with the well established tolerability profile of the neurotoxin when injected into head and neck muscles; no new safety events were observed.

Debate surrounding the PREEMPT studies has centred on the small treatment effect of onaBoNTA relative to placebo, the possibility that blinding was inadequate and the relevance of the evaluated population. Nonetheless, the totality of the data showed that onaBoNTA therapy produced clinically meaningful improvements in headache symptoms, functioning and HR-QOL; on the basis of these trials, it has become the first (and so far only) headache prophylactic therapy to be specifically approved for chronic migraine in the UK and US. Overall, onaBoNTA offers a beneficial, acceptably tolerated and potentially convenient option for the management of this highly disabling condition, for example in patients who are refractory to oral medications used for prophylaxis.

References

  1. 1.
    Goadsby PJ, Lipton RB, Ferrari MD. Migraine: current understanding and treatment. N Engl J Med 2002 Jan 24; 346(4): 257–70PubMedCrossRefGoogle Scholar
  2. 2.
    D’Andrea G, Colavito D, Dalle Carbonare M, et al. Migraine with aura: conventional and non-conventional treatments. Neurol Sci 2011 May; 32 Suppl. 1: S121–129PubMedCrossRefGoogle Scholar
  3. 3.
    Lipton RB, Bigal ME. Migraine: epidemiology, impact, and risk factors for progression. Headache 2005; 45 Suppl. 1: S3–13PubMedCrossRefGoogle Scholar
  4. 4.
    Buse DC, Rupnow MFT, Lipton BB. Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc 2009; 84(5): 422–35PubMedGoogle Scholar
  5. 5.
    Burton WN, Landy SH, Downs KE, et al. The impact of migraine and the effect of migraine treatment on workplace productivity in the United States and suggestions for future research. Mayo Clin Proc 2009; 84(5): 436–45PubMedGoogle Scholar
  6. 6.
    Lipton RB. Chronic migraine, classification, differential diagnosis, and epidemiology. Headache 2011; 51 Suppl. 2: 77–83PubMedCrossRefGoogle Scholar
  7. 7.
    Manack AN, Buse DC, Lipton RB. Chronic migraine: epidemiology and disease burden. Curr Pain Headache Rep 2011 Feb; 15(1): 70–8PubMedCrossRefGoogle Scholar
  8. 8.
    Manack A, Turkel C, Silberstein S. The evolution of chronic migraine: classification and nomenclature. Headache 2009; 49: 1206–13PubMedCrossRefGoogle Scholar
  9. 9.
    Oleson J, Bousser M-G, Diener H-C, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006; 26: 742–6CrossRefGoogle Scholar
  10. 10.
    Bigal ME, Lipton RB. Overuse of acute migraine medications and migraine chronification. Curr Pain Headache Rep 2009 Aug; 13(4): 301–7PubMedCrossRefGoogle Scholar
  11. 11.
    Tepper SJ, Tepper DE. Breaking the cycle of medication overuse headache. Cleve Clin J Med 2010 Apr; 77(4): 236–42PubMedCrossRefGoogle Scholar
  12. 12.
    Bigal M, Rapoport A, Sheftell F, et al. The International Classification of Headache Disorders revised criteria for chronic migraine-field testing in a headache specialty clinic. Cephalalgia 2007; 27: 230–4PubMedCrossRefGoogle Scholar
  13. 13.
    Natoli JL, Manack A, Dean B, et al. Global prevalence of chronic migraine: a systematic review. Cephalagia 2010; 30(5): 599–609Google Scholar
  14. 14.
    Bigal ME, Rapoport AM, Lipton RB, et al. Assessment of migraine disability using the migraine disability assessment (MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine. Headache 2003 Apr; 43(4): 336–42PubMedCrossRefGoogle Scholar
  15. 15.
    Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS). Cephalalgia 2011; 31(3): 301–15PubMedCrossRefGoogle Scholar
  16. 16.
    Meletiche DM, Lofland JH, Young WB. Quality-of-life differences between patients with episodic and transformed migraine. Headache 2001 Jun; 41(6): 573–8PubMedCrossRefGoogle Scholar
  17. 17.
    Buse DC, Manack A, Serrano D, et al. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry 2010; 81: 428–32PubMedCrossRefGoogle Scholar
  18. 18.
    Ferrari A, Leone S, Vergoni AV, et al. Similarities and differences between chronic migraine and episodic migraine. Headache 2007; 47: 65–72PubMedCrossRefGoogle Scholar
  19. 19.
    Munakata J, Hazard E, Serrano D, et al. Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache 2009 Apr; 49(4): 498–508PubMedCrossRefGoogle Scholar
  20. 20.
    Thakker MM, Rubin PAD. Pharmacology and clinical applications of botulinum toxins A and B. Int Ophthalmol Clin 2004; 44(3): 147–63PubMedCrossRefGoogle Scholar
  21. 21.
    Verheyden J, Blitzer A, Brin MF. Other noncosmetic uses of BOTOX. Semin Cutan Med Surg 2001 Jun; 20(2): 121–6PubMedCrossRefGoogle Scholar
  22. 22.
    Schulte-Mattler WJ. Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. CNS Drugs 2008; 22(9): 725–38PubMedCrossRefGoogle Scholar
  23. 23.
    Brin MF. Development of future indications for BOTOX. Toxicon 2009 Oct; 54(5): 668–74PubMedCrossRefGoogle Scholar
  24. 24.
    BOTOX 100 units: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/112/SPC/BOTOX+100+units/ [Accessed 2011 Nov 1]
  25. 25.
    BOTOX 50 units: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/20564/SPC/BOTOX+50+units/ [Accessed 2011 Nov 1]
  26. 26.
    BOTOX 200 units: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/22562/SPC/Botox+200+units/[Accessed 2011 Nov 1]
  27. 27.
    Vistabel: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/17580/SPC/Vistabel/ [Accessed 2011 Nov 16]
  28. 28.
    BOTOX (onabotulinumtoxinA) for injection, for intramuscular, intradetrusor, or intradermal use: US prescribing information [online]. Available from URL: http://www.allergan.com/assets/pdf/botox_pi.pdf [Accessed 2011 Nov 2]
  29. 29.
    BOTOX® Cosmetic (onabotulinumtoxinA) for injection: US prescribing information [online]. Available from URL: http://www.allergan.com/assets/pdf/botox_cosmetic_pi.pdf [Accessed 2011 Nov 16]
  30. 30.
    Blumenfeld A, Silberstein SD, Dodick DW, et al. Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache 2010; 50(9): 1406–18PubMedCrossRefGoogle Scholar
  31. 31.
    Frampton JE, Easthope SE. Botulinum toxin A (Botox cosmetic): a review of its use in the treatment of glabellar frown lines. Am J Clin Dermatol 2003; 4(10): 709–25PubMedCrossRefGoogle Scholar
  32. 32.
    Aoki KR. Pharmacology and immunology of botulinum neurotoxins. Int Ophthalmol Clin 2005; 45(3): 25–37PubMedCrossRefGoogle Scholar
  33. 33.
    Turton K, Chaddock JA, Acharya KR. Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem Sci 2002 Nov; 27(11): 552–8PubMedCrossRefGoogle Scholar
  34. 34.
    Dressler D, Adib Saheri F, Reis Barbosa E. Botulinum toxin: mechanisms of action. Arq Neuropsiquiatr 2005; 63(1): 180–5PubMedCrossRefGoogle Scholar
  35. 35.
    Wollina U. Botulinum toxin: non-cosmetic indications and possible mechanisms of action. J Cutan Aesthet Surg 2008 Jan; 1(1): 3–6PubMedCrossRefGoogle Scholar
  36. 36.
    Aoki KR. Review of a proposed mechanism for the anti-nociceptive action of botulinum toxin type A. Neurotoxicol 2005 Oct; 26(5): 785–93CrossRefGoogle Scholar
  37. 37.
    Aoki KR, Francis J. Updates on the antinociceptive mechanism hypothesis of botulinum toxin A. Parkinsonism Relat D 2011 Nov; 17 Suppl. 1: S28–33CrossRefGoogle Scholar
  38. 38.
    Pavone F, Luvisetto S. Botulinum neurotoxin for pain management: insights from animal models. Toxins 2010; 2: 2890–913PubMedCrossRefGoogle Scholar
  39. 39.
    Durham PL, Cady R. Insights into the mechanism of ona-botulinumtoxinA in chronic migraine. Headache 2011 Nov 14; 51(10): 1573–7PubMedCrossRefGoogle Scholar
  40. 40.
    Malik A, Burstein R. Peripheral and central sensitization during migraine. Funct Neurol 2000; 15 Suppl.: 28–35Google Scholar
  41. 41.
    Mathew NT. Pathophysiology of chronic migraine and mode of action of preventive medications. Headache 2011; 51 Suppl. 2: 84–92PubMedCrossRefGoogle Scholar
  42. 42.
    Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 2003; 43 Suppl. 1: S9–15PubMedCrossRefGoogle Scholar
  43. 43.
    Kulthia AS, Barrodale PM, Turkel CC, et al. To study the effect of prophylaxis with onabotulinumtoxinA on the pain free response to 100 mg of sumatriptan in a group of chronic migraine patients [abstract no. P136]. 53rd Annual Scientific Meeting of the American Headache Society; 2011 Jun 2–5; Washington, DCGoogle Scholar
  44. 44.
    Naumann M, Carruthers A, Carruthers J, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications. Mov Disord 2010 Oct 15; 25(13): 2211–8PubMedCrossRefGoogle Scholar
  45. 45.
    Medicines and Healthcare Products Regulatory Agency. Botox (Botulinum toxin type A): PL 00426/0074-0105; PL 00426/0118-0025; PL 00426/0119-0007: UKPAR [online]. Available from URL: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con108643.pdf [Accessed 2011 Oct 28]
  46. 46.
    Allergan. A study using botulinum toxin type A as headache prophylaxis for migraine patients with frequent headaches [ClinicalTrials.gov identifier NCT00156910]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Nov 2]
  47. 47.
    Allergan. A study using botulinum toxin type A as headache prophylaxis for migraine patients with frequent headaches [ClinicalTrials.gov identifier NCT00168428]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Nov 2]
  48. 48.
    Aurora S, Dodick D, Turkel C, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PRE-EMPT 1 trial. Cephalalgia 2010; 30(7): 793–803PubMedCrossRefGoogle Scholar
  49. 49.
    Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 2010; 30(7): 804–14PubMedCrossRefGoogle Scholar
  50. 50.
    Dodick DW, Turkel CC, Degryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 2010; 50(6): 921–36PubMedCrossRefGoogle Scholar
  51. 51.
    Aurora SK, Winner P, Freeman MC, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache 2011; 51: 1358–73PubMedCrossRefGoogle Scholar
  52. 52.
    Lipton RB, Varon SF, Grosberg B, et al. OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine. Neurology 2011 Oct 11; 77(15): 1465–72PubMedCrossRefGoogle Scholar
  53. 53.
    Aurora SK, Mathew NT, Forner SD, et al. Onabotuli-numtoxinA for treatment of chronic migraine: analysis of the 56-week PREEMPT 1 trial [abstract no. P06.250]. 62nd Annual Meeting of the American Academy of Neurology; 2010 Apr 10–17; Toronto (ON)Google Scholar
  54. 54.
    Dodick DW, Gawel MJ, Agosti RM, et al. OnabotulinumtoxinA for treatment of chronic migraine: analysis of the 56-week PREEMPT 2 trial [abstract no. P06.251]. 62nd Annual Meeting of the American Academy of Neurology; 2010 Apr 10–17; Toronto (ON)Google Scholar
  55. 55.
    Therapeutic Goods Administration. Australian public assessment report for botulinum toxin type A [online]. Available from URL: http://www.tga.gov.au/pdf/auspar/auspar-botox.pdf [Accessed 2011 Dec 2]
  56. 56.
    Mathew NT, Frishberg BM, Gawel M, et al. Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Headache 2005; 45(4): 293–307PubMedCrossRefGoogle Scholar
  57. 57.
    Silberstein SD, Stark SR, Lucas SM. Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 2008; 80(9): 1126–37CrossRefGoogle Scholar
  58. 58.
    Mathew NT, Jaffri SFA. A double-blind comparison of onabotulinumtoxinA (BOTOX) and topiramate (TOPA-MAX) for the prophylactic treatment of chronic migraine: a pilot study. Headache 2009; 49(10): 1466–78PubMedCrossRefGoogle Scholar
  59. 59.
    Cady RK, Schreiber CP, Porter JAH, et al. A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine. Headache 2011; 51(1): 21–32PubMedCrossRefGoogle Scholar
  60. 60.
    Coeytaux RR, Kaufman JS, Chao R, et al. Four methods of estimating the minimal important difference score were compared to establish a clinically significant change in Headache Impact Test. J Clin Epidemiol 2006; 59: 374–80PubMedCrossRefGoogle Scholar
  61. 61.
    Dodick DW, Silberstein S, Saper J, et al. The impact of topiramate on health-related quality of life indicators in chronic migraine. Headache 2007; 47: 1398–408PubMedCrossRefGoogle Scholar
  62. 62.
    Markert RJ, Solomon GD. OnabotulinumtoxinA for treatment of chronic migraine. Headache 2011; 51(6): 1002–3PubMedCrossRefGoogle Scholar
  63. 63.
    Modi S, Lowder DM. Medications for migraine prophy-laxis. Am Fam Phys 2006 Jan 1; 73(1): 72–8Google Scholar
  64. 64.
    Shürks M, Diener HC, Goadsby P, et al. Update on the prophylaxis of migraine. Curr Treat Options Neurol 2008; 10(1): 20–9CrossRefGoogle Scholar
  65. 65.
    Fenstermacher N, Levin M, Ward T. Pharmacological prevention of migraine. BMJ 2011; 342(7796): 540–3Google Scholar
  66. 66.
    Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine: revised report of an EFNS task force. Eur J Neurol 2009; 16: 968–81PubMedCrossRefGoogle Scholar
  67. 67.
    Antonachi F, Dumitrache C, De Cillis I, et al. A review of European treatment guidelines for migraine. J Headache Pain 2010 Feb; 11(1): 13–9CrossRefGoogle Scholar
  68. 68.
    Pringsheim T, Davenport WJ, Becker WJ. Prophylaxis of migraine headache. CMAJ 2010; 182(7): E269–276PubMedGoogle Scholar
  69. 69.
    Garza I, Swanson JW. Prophylaxis of migraine. Neuropsychiatr Dis Treat 2006; 2: 281–91PubMedCrossRefGoogle Scholar
  70. 70.
    British Association for the Study of Headache. Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type headache, cluster headache and medication-overuse headache: 3rd edition (1st revision) [online]. Available from URL: http://217.174.249.183/upload/NS_BASH/2010_BASH_guidelines.pdf [Accessed 2012 Feb 22]
  71. 71.
    Silvestri M, Bartolini M, Coccia M, et al. Topiramate in the treatment of chronic migraine. Expert Opin Pharmacother 2006; 7: 1085–95CrossRefGoogle Scholar
  72. 72.
    Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 2007; 47: 170–80PubMedCrossRefGoogle Scholar
  73. 73.
    North East Treatment Advisory Group. Botulinum toxin (Botox®) for chronic migraine [online]. Available from URL: http://www.nyrdtc.nhs.uk/docs/eva/Botox%20for%20chronic%20migraine%20-%20NETAG%20appraisal%20report%20-Sept%202011-%20WEB%20VERSION.pdf [Accessed 2011 Dec 3]Google Scholar
  74. 74.
    Parsekyan D. Migraine prophylaxis in adult patients. West J Med 2000 Nov; 173(5): 341–5PubMedCrossRefGoogle Scholar
  75. 75.
    Vargas BB, Dodick DW. The face of chronic migraine: epidemiology, demographics, and treatment strategies. Neurol Clin 2009; 27: 467–79PubMedCrossRefGoogle Scholar
  76. 76.
    Reed KL, Black SB, Banta II CJ, et al. Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: initial experience. Cephalalgia 2010; 30(3): 260–71PubMedGoogle Scholar
  77. 77.
    Weibelt S, Andress-Rothrock D, King W, et al. Suboccipital nerve blocks for suppression of chronic migraine: safety, efficacy, and predictors of outcome. Headache 2010; 50: 1041–4PubMedCrossRefGoogle Scholar
  78. 78.
    Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia 2005; 25: 82–6PubMedCrossRefGoogle Scholar
  79. 79.
    Bigal ME, Serrano D, Reed M, et al. Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment. Neurology 2008; 71: 559–66PubMedCrossRefGoogle Scholar
  80. 80.
    Dodick DW, Turkel CC, Degryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: a response. Headache 2011; 51(6): 1005–8PubMedCrossRefGoogle Scholar
  81. 81.
    Olesen J, Tfelt-Hansen P. Licence for Botox in so-called chronic migraine. Lancet 2010; 376(9755): 1825–6PubMedCrossRefGoogle Scholar
  82. 82.
    Torgovnick J. OnabotulinumtoxinA for the treatment of chronic migraine not quite there. Cephalalgia 2011; 31(3): 377PubMedCrossRefGoogle Scholar
  83. 83.
    Silberstein S, Tfelt-Hansen P, Dodick DW, et al. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia 2008; 28: 484–95PubMedCrossRefGoogle Scholar
  84. 84.
    Aurora S, Diener HC, Dodick D. Reply: clinical trials on onabotulinumtoxinA for the treatment of chronic migraine. J Headache Pain 2011; 12(2): 137–8PubMedCrossRefGoogle Scholar
  85. 85.
    Russell MB. Clinical trials on onabotulinumtoxinA for the treatment of chronic migraine. J Headache Pain 2011; 12(2): 135–6PubMedCrossRefGoogle Scholar
  86. 86.
    Freitag FG, Diamond S, Diamond M, et al. Botulinum toxin type A in the treatment of chronic migraine without medication overuse. Headache 2008 Feb; 48(2): 201–9PubMedGoogle Scholar
  87. 87.
    Burstein R, Cutrer MF, Yarnitsky MF. The development of cutaneous allodynia during a migraine attack: clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 2000; 123: 1703–9PubMedCrossRefGoogle Scholar
  88. 88.
    Mathew P, Cutrer FM, Garza I. Cutaneous allodynia as a prognostic factor in the treatment of migraine with Botulinum toxin [abstract no. PO-69]. 52nd Annual Scientific Meeting of the American Headache Society; 2010 Jun 24–27; Los Angeles (CA)Google Scholar
  89. 89.
    Evers S, Olesen J. Botulinum toxin in headache treatment: the end of the road? Cephalalgia 2006; 26(7): 769–71PubMedCrossRefGoogle Scholar
  90. 90.
    Naumann M, So Y, Argoff CE. for the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. 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(19): 1707–14Google Scholar
  91. 91.
    Finkel AG. Botulinum toxin and the treatment of headache: a clinical review. Headache 2011; 51(10): 1565–72PubMedCrossRefGoogle Scholar
  92. 92.
    Schoenen J. Botulinum toxin in headache treatment: finally a promising path? Cephalalgia 2010; 30(7): 771–3PubMedCrossRefGoogle Scholar
  93. 93.
    Blumenfeld A, Evans RW. OnabotulinumtoxinA for chronic migraine. Headache. Epub 2012 Jan 23Google Scholar
  94. 94.
    Silberstein S, Dodick DW, Degryse RE, et al. The percent of chronic migraine patients who responded to onabotulinumtoxinA treatment per treatment cycle in the PREEMPT clinical program. 15th Congress of the European Federation of Neurological Societies; 2011 Sep 10–13; BudapestGoogle Scholar
  95. 95.
    Robertson CE, Garza I. Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A) in migraine. Neuropsychiatr Dis Treat 2012; 8: 35–48PubMedCrossRefGoogle Scholar
  96. 96.
    Scottish Medicines Consortium. Botulinum toxin type A, 50 unit, 100 unit and 200 unit powder for solution for injection. SMC No. (692/11) [online]. Available from URL: http://www.scottishmedicines.org.uk/files/advice/botulinum_toxin_type_A_Botox_FINAL_MARCH_2011_AMENDED_22.03_for_website.pdf [Accessed 2011 Dec 3]
  97. 97.
    Rothrock J, Andress-Rothrock D, Hanlon C, et al. Is ona-botulinumtoxinA a cost-effective therapy for chronic migraine? [abstract PS2-163]. 15th Congress of the International Headache Society; 2011 Jun 23–26; BerlinGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.AdisMairangi Bay, North Shore 0754, AucklandNew Zealand

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