Skip to main content

Advertisement

SpringerLink
Log in

OnabotulinumtoxinA in Migraine and Other Headaches: Review and Update

  • Headache (JR Couch, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of the review

The role of onabotulinumtoxinA in headache management was serendipitously found over a decade ago and approved for chronic migraine in 2010 based on pivotal studies. The purpose of this review is to highlight the impact on headache and other health parameters which is critically reviewed, as well as the putative mechanisms of action.

Recent findings

OnabotulinumtoxinA is effective in migraine, not only headache frequency and pain intensity but also other health parameters including quality of life. Tolerability is high and benefit/cost analysis is favorable. It should be considered off-label in refractory trigeminal neuralgia and post-herpetic neuralgia but further research in these areas. Ongoing investigation of onabotulinumtoxinA in cluster headache is too preliminary for recommendation of use but promising. Recent and future developments in other headache disorders are discussed.

Summary

OnabotulinumtoxinA has been approved for migraine almost a decade ago and been proven beneficial not only on headache parameters but other health outcomes. Its role as adjuvant is being studied and emerging in other headache syndromes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, (beta version). Cephalalgia. 2013;33(9):629–808.

    Article  Google Scholar 

  2. Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ. TOPMAT-MIG-201(TOP-CHROME) Study Group. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27(7):814–23.

    Article  Google Scholar 

  3. Silberstein S, Lipton R, Dodick D, Freitag F, Mathew N, Brandes J, et al. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures. Headache. 2009;49(8):1153–62.

    Article  Google Scholar 

  4. Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–34.

    Article  CAS  Google Scholar 

  5. Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–22.

    Article  CAS  Google Scholar 

  6. Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211–21.

    Article  CAS  Google Scholar 

  7. Binder W, Brin MF, Blitzer A, Schenrock L, Diamond B. Botulinum toxin type A (BTX-A) for migraine: an open label assessment [abstract]. Mov Disord. 1998;13(suppl 2):241.

    Google Scholar 

  8. 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(6):445–50.

    Article  CAS  Google Scholar 

  9. •• Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, 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(7):793–803. A pivotal study in FDA-approval of onabotulinumtoxinA in treatment of chronic migraine.

    Article  CAS  Google Scholar 

  10. •• Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, 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):804–14. A pivotal study in FDA-approval of onabotulinumtoxinA in treatment of chronic migraine.

    Article  Google Scholar 

  11. Mathew NT, Frishberg BM, Gawel M, Dimitrova R, Gibson J, Turkel C. 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.

    Article  Google Scholar 

  12. Silberstein SD, Stark SR, Lucas SM, Christie SN, Degryse RE, Turkel CC. Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005;80:1126–37.

    Article  CAS  Google Scholar 

  13. Blumenfeld A, Silberstein SD, Dodick DW, Aurora SK, Turkel CC, Binder WJ. 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):1406–18.

    Article  Google Scholar 

  14. Janis JE, Barker JC, Palettas M. Targeted peripheral nerve-directed onabotulinumtoxin A injection for effective long-term therapy for migraine headache. Plast Reconstr Surg Glob Open. 2017;5(3):e1270.

    Article  Google Scholar 

  15. Matharu M, Halker R, Pozo-Rosich P, DeGryse R, Manack Adams A, Aurora SK. The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis. J Headache Pain. 2017;18(1):78.

    Article  Google Scholar 

  16. Blumenfeld AM, Stark RJ, Freeman MC, Orejudos A, Manack Adams A. Long-term study of the efficacy and safety of onabotulinumtoxinA for the prevention of chronic migraine: COMPEL study. J Headache Pain. 2018;19(1):13.

    Article  Google Scholar 

  17. Santoro A, Fontana A, Miscio AM, Zarrelli MM, Copetti M, Leone MA. Quarterly repeat cycles of onabotulinumtoxinA in chronic migraine patients: the benefits of the prolonged treatment on the continuous responders and quality-of-life conversion rate in a real-life setting. Neurol Sci. 2017;38(10):1779–89.

    Article  Google Scholar 

  18. Guerzoni S, Pellesi L, Baraldi C, Cainazzo MM, Negro A, Martelletti P, et al. Long-term treatment benefits and prolonged efficacy of onabotulinumtoxinA in patients affected by chronic migraine and medication overuse headache over 3 years of therapy. Front Neurol. 2017;8:586.

    Article  Google Scholar 

  19. Lipton RB, Varon SF, Grosberg B, McAllister PJ, Freitag F, Aurora SK, et al. OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine. Neurology. 2011;77(15):1465–72.

    Article  CAS  Google Scholar 

  20. Rothrock JF, Bloudek LM, Houle TT, Andress-Rothrock D, Varon SF. Real-world economic impact of onabotulinumtoxinA in patients with chronic migraine. Headache. 2014;54(10):1565–73.

    Article  Google Scholar 

  21. Negro A, Curto M, Lionetto L, Crialesi D, Martelletti P. OnabotulinumtoxinA 155 U in medication overuse headache: a two years prospective study. Springerplus. 2015;4:286.

    Article  Google Scholar 

  22. Maasumi K, Thompson NR, Kriegler JS, Tepper SJ. Effect of OnabotulinumtoxinA injection on depression in chronic migraine. Headache. 2015;55(9):1218–24.

    Article  Google Scholar 

  23. Bratbak DF, Nordgard S, Nordgard S, Linde M, Dodick D, Aschehoug I, et al. Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic migraine. Cephalalgia. 2017;37(4):356–64.

    Article  Google Scholar 

  24. Domínguez C, Pozo-Rosich P, Torres-Ferrús M, Hernández-Beltrán N, Jurado-Cobo C, González-Oria C, et al. OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective multicentre descriptive study. Eur J Neurol. 2018;25(2):411–6.

    Article  Google Scholar 

  25. Sandrini G, De Icco R, Tassorelli C, Smania N, Tamburin S. Botulinum neurotoxin type a for the treatment of pain: not just in migraine and trigeminal neuralgia. J Headache Pain. 2017;18(1):38.

    Article  Google Scholar 

  26. Mense S. Neurobiological basis for the use of botulinum toxin in pain therapy. J Neurol. 2004;251(supplement 1):1–7.

    Article  CAS  Google Scholar 

  27. Bittencourt da Silva L, Nørgaard Poulsen J, Arendt-Nielsen L, Gazerani P. Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells. J Cell Mol Med. 2015;19(8):1900–9.

    Article  Google Scholar 

  28. Shimizu T, Shibata M, TorUmi H, et al. Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. Neurobiol Dis. 2012;48(3):367–78.

    Article  CAS  Google Scholar 

  29. Ferrandiz-Huertas C, Mathivanan S, Wolf CJ, Devesa I, Ferrer-Montiel A. Trafficking of thermo TRP channels. Membranes. 2014;4(3):525–64.

    Article  Google Scholar 

  30. Mazzocchio R, Caleo M. More than at the neuromuscular synapse: actions of botulinum neurotoxin a in the central nervous system. Neuroscientist. 2015;21(1):44–61.

    Article  Google Scholar 

  31. Paracka L, Kollewe K, Wegner F, Dressler D. Strategies to decrease injection site pain in botulinum toxin therapy. J Neural Transm. 2017;124(10):1213–12116.

    Article  CAS  Google Scholar 

  32. Schulte-Mattler WJ, Krack P. BoNTTH Study Group. Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study. Pain. 2004;109(1–2):110–4.

    Article  CAS  Google Scholar 

  33. Schmitt WJ, Slowey E, Fravi N, Weber S, Burgunder JM. Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial. Headache. 2001;41(7):658–64.

    Article  CAS  Google Scholar 

  34. Lampl C, Rudolph M, Bräutigam E. OnabotulinumtoxinA in the treatment of refractory chronic cluster headache. J Headache Pain. 2018;19(1):45.

    Article  Google Scholar 

  35. • Aschehoug I, Bratbak DF, Tronvik EA. Long-term outcome of patients with intractable chronic cluster headache treated with injection of onabotulinum toxin a toward the sphenopalatine ganglion - an observational study. Headache. 2018;58(10):1519–29. Original and promising approach for cluster headache treatment.

    Article  Google Scholar 

  36. Lu J, Xu YY, Zhang QL, Luo WF. Efficacy and safety of botulinum toxin type A in treating patients of advanced age with idiopathic trigeminal neuralgia. Pain Res Manag. 2018;2018:7365148 eCollection.

    Google Scholar 

  37. Verma G. Role of botulinum toxin type-A (BTX-A) in the management of trigeminal neuralgia. Pain Res Treat. 2013;2013:831094.

    PubMed  PubMed Central  Google Scholar 

  38. Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in post-herpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. Clin J Pain. 2013;29(10):857–64.

    Article  Google Scholar 

  39. Jabbari B, Machado D. Treatment of refractory pain with botulinum toxins -an evidence-based review. Pain Med. 2011;12(11):1594–606.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of California, Davis, 4160, Y St., No. 3700, Sacramento, CA, 95817, USA

    Marc E. Lenaerts MD, FAHS & Tiffany H. Green MD

Authors
  1. Marc E. Lenaerts MD, FAHS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiffany H. Green MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc E. Lenaerts MD, FAHS.

Ethics declarations

Conflict of Interest

Marc Lenaerts is a member of Speakers Bureaus of Amgen, Allergan, and Teva Pharmaceuticals. Tiffany Green declares no potential conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lenaerts, M.E., Green, T.H. OnabotulinumtoxinA in Migraine and Other Headaches: Review and Update. Curr Treat Options Neurol 21, 21 (2019). https://doi.org/10.1007/s11940-019-0561-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11940-019-0561-6

Keywords

Search

Navigation