Botulinum Toxin for Migraine

  • Maria Eduarda Nobre
  • Marcelo Cedrinho Ciciarelli
  • Jano Alves SouzaEmail author
Living reference work entry

Latest version View entry history

Part of the Clinical Approaches and Procedures in Cosmetic Dermatology book series (CAPCD)


The use of onabotulinumtoxinA in headaches starts in 1997 with exploratory studies for migraine and other headache subtypes. At the same time, laboratory research explored the nonmotor effects of onabotulinumtoxinA.

However, the efficacy was demonstrated just for chronic migraine (CM) and the use was approved in 2010 based on two studies, PREEMPT 1 and 2. These studies consisted of a 24-week randomized, double-blind, placebo-controlled phase followed by a 32-week onabotulinumtoxinA open-label phase. Study injections were given at 31 fixed and 8 optional sites with 5U in each site (total 155U to 195U, mean 165U) across seven head and neck muscle areas (procerus, corrugator, frontalis, temporalis, occipitalis, cervical paraspinal, and trapezius), each 12 weeks.

OnabotulinumtoxinA has shown a safe and effective prophylactic treatment option for patients with CM. Accurate target muscle localization and injection angles and depths are required to achieve optimal outcomes and to minimize adverse events.


Headache Chronic migraine OnabotulinumtoxinA 


  1. Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793–803.CrossRefGoogle Scholar
  2. Binder WJ, Blitzer A, Brin MF. Treatment of hyperfunctional lines of the face with botulinum toxin A. Dermatol Surg. 1998a;24:1198–205.PubMedGoogle Scholar
  3. Binder WJ, et al. Botulinum toxin type A (BTX-A) for migraine: an open label assessment. Mov Disord. 1998b;13:241. (Abstract)Google Scholar
  4. Binder WJ, et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg. 2000;123:669–76.CrossRefGoogle Scholar
  5. Blumenfeld A, Bloudek L, Becker W, Buse D, Varon S, Maglinte G. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II). Headache. 2013;53:644–55.CrossRefGoogle Scholar
  6. Blumenfeld AM, Silberstein SD, Dodick DW, Aurora SK, Brin MF, Binder WJ. Insights into the functional anatomy behind the PREEMPT injection paradigm: guidance on achieving optimal outcomes. Headache. 2017;57:766–77.CrossRefGoogle Scholar
  7. Brin MF, Blitzer A. History of onabotulinumtoxinA therapeutic. In: Carruthers A, Carruthers J, editors. Botulinum toxin. London: Saunders Elsevier; 2013. p. 6–12.Google Scholar
  8. Diener HC, Bussone G, Van Oene JC, TOPMAT-MIG-201(TOP-CHROME) Study Group, et al. Topiramate reduces headache days in chronic migraine: A randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27:814–23. Erratum in: Cephalalgia 2007; 27(8):962.CrossRefGoogle Scholar
  9. Diener HC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30:804–14.CrossRefGoogle Scholar
  10. Erbguth FJ, Naumann M. Historical aspects of botulinum toxin: Justinus Kerner (1786–1862) and the “sausage poison”. Neurology. 1999;53:1850–3.CrossRefGoogle Scholar
  11. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.CrossRefGoogle Scholar
  12. Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol. 2010;6(10):573–82.CrossRefGoogle Scholar
  13. Lamanna C, McElroy OE, Eklund HW. The purification and crystallization of Clostridium botulinum type A toxin. Science. 1946;103:613–4.CrossRefGoogle Scholar
  14. Lawrence GW, Dolly JO. Multiple forms of SNARE complexes in exocytosis from chromaffin cells: effects of Ca (2+), MgATP and botulinum toxin type A. J Cell Sci. 2002;115:667–73.PubMedGoogle Scholar
  15. Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55(Suppl 2):103–22. quiz 123–126CrossRefGoogle Scholar
  16. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646–57.CrossRefGoogle Scholar
  17. Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002;58:885–94.CrossRefGoogle Scholar
  18. Magalhaes E, Menezes C, Cardeal M, et al. Botulinum toxin type A versus amitriptyline for the treatment of chronic daily migraine. Clin Neurol Neurosurg. 2010;112:463–6.CrossRefGoogle Scholar
  19. Mathew NT, et al. Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Headache. 2005;45:293–307.CrossRefGoogle Scholar
  20. Riesco N, Cernuda-Morollon E, Martınez-Camblor P, Perez-Alvarez AI, Verano L, Garcıa-Cabo C, Serrano-Pertierra E, Pascual J. Relationship between serum levels of VIP, but not of CGRP, and cranial autonomic parasympathetic symptoms: a study in chronic migraine patients. Cephalalgia. 2017;37(9):823–7.CrossRefGoogle Scholar
  21. Scott AB. Botulinum toxin injection in to extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus. 1980;17:21–5.PubMedGoogle Scholar
  22. Straube A, Pfaffenrath V, Ladwig KH, et al. Prevalence of chronic migraine and medication overuse headache in Germany – the German DMKG headache study. Cephalalgia. 2010;30:207–13.CrossRefGoogle Scholar
  23. Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015;6(3):115–23.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Eduarda Nobre
    • 1
  • Marcelo Cedrinho Ciciarelli
    • 2
  • Jano Alves Souza
    • 3
    Email author
  1. 1.Neurological Clinic Maria Eduarda NobreRio de JaneiroBrazil
  2. 2.Faculdade de Medicina Barão de MauáRibeirão Preto, São PauloBrazil
  3. 3.Universidade Federal FluminenseNiteróiBrazil

Personalised recommendations