Skip to main content

Advertisement

Log in

Beta-Blockers for Migraine Prevention: a Review Article

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

Abstract

Purpose of review

This review seeks to establish the role of beta-blockers (B-adrenergic receptor antagonists) in the pathophysiology of migraine prophylaxis, compare the efficacy of this group of medications with other common prophylactic agents, and also explore the relative benefits of using individual beta-blockers compared with others.

Recent findings

New evidence supports beta-blockers having several mechanisms of action in migraine prophylaxis. Numerous trials reveal significant clinical differences between various beta-blockers in migraine prophylaxis and that commonly used doses of beta-blockers are not optimal. There are also updated guidelines regarding beta-blocker use in migraine prophylaxis.

Summary

Beta-blockers appear to have several mechanisms of action in migraine prophylaxis. We found extensive evidence supporting beta-blockers being effective in migraine prophylaxis. These are often not used at optimum doses; however, when they are, they compare generally favorably compared with other classes of medications. More recent evidence appears to show a relatively favorable side effect profile of beta-blockers compared with previous reports (Barron et al. IJC 163:3572–3579, 2013).

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

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. Koehler PJ, Tfelt Hansen PC. History of methysergide. Cephalalgia. 2008;N28(11):1126–35.

    Article  Google Scholar 

  2. Rabkin R, Stables D, Levin N, et al. The prophylactic value of propranolol in angina pectoris. Am J Cardiol. 1966;18:370–83.

    Article  CAS  PubMed  Google Scholar 

  3. Prichard BNC. Hypotensive action of pronethalol. Br Med J. 1964;1:1227–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Quirke V. Putting theory into practice: James black, receptor theory and the development of the beta-blockers at ICI, 1958–1978. Med Hist. 2006;50:69–92.

    Article  PubMed  PubMed Central  Google Scholar 

  5. • Sprenger T, Viana M, Tassorelli C. Current prophylactic medications for migraine and their potential mechanisms of action. Neurotherapeutics. 2018;15:313–23 A recent and comprehensive review of prophylactic migraine medications and their possible mechanism of action related to migraine pathophysiology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hieble JP. Adrenoceptor subclassification: an approach to improved cardiovascular therapeutics. Pharm Acta Helv. 2000;74:163–71.

    Article  CAS  PubMed  Google Scholar 

  7. Schoenen J, Ambrosini A, Sandor PS, et al. Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance. Clin Neurophysiol. 2003;114:955–72.

    Article  PubMed  Google Scholar 

  8. Nyrke T, Kangasniemi P, Lang AH, Petersen E. Steady-state visual evoked potentials during migraine prophylaxis by propranolol and femoxetine. Acta Neurol Scand. 1984;69:9–14.

    Article  CAS  PubMed  Google Scholar 

  9. Gehrwig M, Niehaus L, Stude P, et al. Beta-blocker migraine prophylaxis affects the excitability of the visual cortex as revealed by transcranial magnetic stimulation. J Headache Pain. 2012;13:83–9.

    Article  Google Scholar 

  10. •• Jackson J, Cogbill E, Santana-Davila R, et al. A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PLoS One. 2015;10:7 A very comprehensive systematic meta-analysis of historical and more recent publications observing the efficacy of common prophylactic migraine medications. Includes publications comparing different medications with each other.

    Google Scholar 

  11. Diener HC, Scholz E, Dichgans J, Gerber WD, Jäck A, Bille A, et al. Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potential. Ann Neurol. 1989;25:125–30.

    Article  CAS  PubMed  Google Scholar 

  12. Maertens de Noordhout A, Timsit-Berthier M, Timsit M, et al. Effects of beta blockade on contingent negative variation in migraine. Ann Neurol. 1987;21:111–2.

    Article  CAS  PubMed  Google Scholar 

  13. Siniatchkin M, Andrasik F, Kropp P, Niederberger U, Strenge H, Averkina N, et al. Central mechanisms of controlled-release metoprolol in migraine: a double-blind, placebo- controlled study. Cephalalgia. 2007;27:1024–32.

    Article  CAS  PubMed  Google Scholar 

  14. Schoenen J, Maertens de Noordhout A, Timsit-Berthier M, et al. Contingent negative variation and efficacy of beta-blocking agents in migraine. Cephalalgia. 1986;6:229–33.

    Article  CAS  PubMed  Google Scholar 

  15. Sandor PS, Afra J, Ambrosini A, Schoenen J. Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials. Headache. 2000;40:30–5.

    Article  CAS  PubMed  Google Scholar 

  16. Coppola G, Iacovelli E, Bracaglia M, Serrao M, di Lorenzo C, Pierelli F. Electrophysiological correlates of episodic migraine chronification: evidence for thalamic involvement. J Headache Pain. 2013;14:76.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Coppola G, Tinelli E, Lepre C, Iacovelli E, di Lorenzo C, di Lorenzo G, et al. Dynamic changes in thalamic microstructure of migraine without aura patients: a diffusion tensor magnetic resonance imaging study. Eur J Neurol. 2014;21:287–e13.

    Article  PubMed  Google Scholar 

  18. Shields KG, Goadsby PJ. Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine? Brain. 2005;128:86–97.

    Article  PubMed  Google Scholar 

  19. Johnson KW, Phebus LA, Cohen ML. Serotonin in migraine: theories, animal models and emerging therapies. Prog Drug Res. 1998;51:219–44.

    Article  CAS  PubMed  Google Scholar 

  20. Longmore J, Maguire JJ, Macleod A, et al. Comparison of the vasoconstrictor effects of the selective 5-HT1D-receptor agonist L-775,606 with the mixed 5-HT1B/1D receptor agonist sumatriptan and 5-HT in human isolated coronary artery. Br J Clin Pharmacol. 2000;49:126–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cruickshank JM, Prichard BNC. Beta-blockers in clinical practice. 1st ed. London: Churchill Livingstone; 1988. p. 177–274.

  22. Ashina M, Bendtsen L, Jensen R, et al. Nitric oxide-induced headache in patients with chronic tension-type headache. Brain. 2000;123:1830–7.

    Article  PubMed  Google Scholar 

  23. • Hebestreit J, May A. The enigma of site of action of migraine preventives: no effect of metoprolol on trigeminal pain processing in patients and healthy controls. J Headache Pain. 2017;18:116 A study using fMRI that appears to suggest that the mechanism of action of metoprolol may be peripheral rather than central. The study has some weaknesses; it only observed subjects after 3 months of starting metoprolol, the dose of metoprolol was relatively low at 75mg daily, and it had a small sample size of 45 subjects. However, it still raises some questions as to our current understanding of the mechanism of action of beta-blockers in migraine.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache. 2012;52:930–45.

    Article  Google Scholar 

  25. Pringsheim T, Davenport W, Mackie G, et al. Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39:1–59.

    Google Scholar 

  26. Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, et al. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009;16:968–81.

    Article  CAS  PubMed  Google Scholar 

  27. •• Tfelt-Hansen P, Agesen FN, Furberg N. Pharmacokinetic variability of drugs used for the prophylactic treatment of migraine. CNS Drugs. 2017;31:389–403 Review evaluating the variability in pharmacokinetics amongst prophylactic migraine medications. Highlights the importance of personalized medicine when choosing treatment options in migraineurs.

    Article  CAS  PubMed  Google Scholar 

  28. Linde K, Rossnagel K. Propranolol for migraine prophylaxis. Cochrane Database Syst Rev. 2004;2:CD003225.

    Google Scholar 

  29. Carroll JD, Reidy M, Savundra PA, Cleave N, McAinsh J. Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. Cephalalgia. 1990;10:101–5.

    Article  CAS  PubMed  Google Scholar 

  30. Al-Qassab HK, Findler LJ. Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo-controlled study. Cephalalgia. 1993;13:128–31.

    Article  CAS  PubMed  Google Scholar 

  31. Gerber WD, Diener HC, Scholz E, Niederberger U. Responder and non-responder to metoprolol, propranolol and nifedipine treatment in migraine prophylaxis: a dose-range study based on time-series analysis. Cephalalgia. 1991;11:37–45.

    Article  CAS  PubMed  Google Scholar 

  32. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study. Neurology. 1994;44:647–51.

    Article  CAS  PubMed  Google Scholar 

  33. Ashtari F, Shaygannejad V, Akbari M. A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis. Acta Neurol Scand. 2008;118:301–5.

    Article  CAS  PubMed  Google Scholar 

  34. Diener HC, Tfelt-Hansen P, Dahlof C, et al. Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2014;251:943–50.

    Google Scholar 

  35. Yadav R, Shukla SK. Propranolol versus topiramate in prophylaxis of migraines among children and adolescents: a randomized, double-blind clinical trial. International Journal of Research in Medical Sciences. 2017;5:4307–11.

    Article  Google Scholar 

  36. Tonekaboni SH, Ghazavi A, Fayyazi A, et al. Prophylaxis of childhood migraine: topiramate versus propranolol. Iran J Child Neuro. 2013;7:9–14.

    Google Scholar 

  37. Olsson JE, Behring JC, Forssman B. Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study. Acta Neurol Scand. 1984;70:160–8.

    Article  CAS  PubMed  Google Scholar 

  38. Tfelt-Hansen P. Timolol vs propranolol vs placebo in common migraine prophylaxis: a double-blind multicenter trial. Acta Neurol Scand. 1984;69:1–8.

    Article  CAS  PubMed  Google Scholar 

  39. Hedman C, Andersen AR, Andersson PG, Gilhus NE, Kangasniemi P, Olsson JE, et al. Symptoms of classic migraine attacks: modifications brought on by metoprolol. Cephalalgia. 1988;8:279–84.

    Article  CAS  PubMed  Google Scholar 

  40. Langoht HD, Gerber WD, Koletzki D, et al. Clomipramine and metoprolol in migraine prophylaxis- a double- blind crossover study. Headache. 1985;25:107–13.

    Article  Google Scholar 

  41. Steiner TJ, Joesph R, Hedman C, et al. Metoprolol in the prophylaxis of migraine: parallel-groups comparison with placebo and dose-ranging follow-up. Headache. 1998;28:15–23.

    Article  Google Scholar 

  42. Stellar S, Ahrens SP, Meibohm MR, et al. Migraine prevention with timolol. A double-blind crossover study. JAMA. 1984;252:2576–80.

    Article  CAS  PubMed  Google Scholar 

  43. Standnes B. The prophylactic effect of timolol versus propranolol and placebo in common migraine: beta-blockers in migraine. Cephalalgia. 1982;2:165–70.

    Article  CAS  PubMed  Google Scholar 

  44. Freitag FG, Diamond S. Nadolol and placebo comparison study in the prophylactic treatment of migraine. J Am Osteopath Assoc. 1984;84:343–7.

    CAS  PubMed  Google Scholar 

  45. Kostis JB, Rosen RC. Central nervous system effect of beta-adrenergic- blocking drugs: the role of ancillary properties. Circulation. 1987;1:204–12.

    Article  Google Scholar 

  46. Sudilovsky A, Elkind AH, Ryan RE Sr, et al. Comparative efficacy of nadolol and propranolol in the management of migraine. Headache. 1987;27:421–6.

    Article  CAS  PubMed  Google Scholar 

  47. Ryan RE Sr, Ryan RE Jr, Sudilovsky A. Nadolol: its use in the prophylactic treatment of migraine. Headache. 1983;23:26–31.

    Article  PubMed  Google Scholar 

  48. Olerud B, Gustavsson CL, Furberg B. Nadolol and propranolol in migraine management. Headache. 1986;26:490–3.

    Article  CAS  PubMed  Google Scholar 

  49. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349.

    Article  CAS  PubMed  Google Scholar 

  50. Ko DT, Hebert PR, Coffee CS, et al. Adverse effects of beta-blocker therapy for patients with heart failure: a quantitative overview of randomized trials. Arch Intern Med. 2004;164:1389–94.

    Article  CAS  PubMed  Google Scholar 

  51. • Lu H, Kam J, Nordin RB, et al. Beta-blocker use and risk of symptomatic bradyarrhythmias: a hospital-based case-control study. J Geriatr Cardiol. 2016;13:749–59 Demonstrates significant risk of symptomatic bradyarrhythmias in older patients. This is important since many patients within this age group (over 64) are currently on beta-blockers for migraine prophylaxis and this risk factor is often not considered.

    PubMed  PubMed Central  Google Scholar 

  52. Frishman WH. Drug therapy. Pindolol: a new beta-adrenoceptor antagonist with partial agonist activity. N Engl J Med. 1983;308:940–4.

    Article  CAS  PubMed  Google Scholar 

  53. Dickstein K, Cohen-Solal A, Filippatos G, et al. Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008;29:2388–442.

    Article  CAS  PubMed  Google Scholar 

  54. Dunlop D, Shanks RG. Selective blockade of adrenoceptive beta receptors in the heart. Br J Pharmacol Chemother. 1968;32:201–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Khosla S, Kunjummen B, Khaleel R. Safety of therapeutic beta-blockade in patients with coexisting bronchospastic airway disease and coronary artery disease. Am J Ther. 2003;10:48–50.

    Article  PubMed  Google Scholar 

  56. Frohlich ED, Tarazi RC, Dustan HP. Peripheral arterial insufficiency. A complication of beta-adrenergic blocking therapy. JAMA. 1969;208:2471–2.

    Article  CAS  PubMed  Google Scholar 

  57. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med. 1991;151:1769.

    Article  CAS  PubMed  Google Scholar 

  58. Thadani U, Whitsett TL. Beta-adrenergic blockers and intermittent claudication. Time for reappraisal. Arch Intern Med. 1991;151:1705–7.

    Article  CAS  PubMed  Google Scholar 

  59. Heintzen MP, Strauer BE. Peripheral vascular effects of beta-blockers. Eur Heart J. 1994;15:2–7.

    Article  PubMed  Google Scholar 

  60. Ko DT, Hebert PR, Coffee CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA. 2002;288:351–7.

    Article  CAS  PubMed  Google Scholar 

  61. Silvestri A, Galetta P, Cerquetani E, et al. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. Eur Heart J. 2003;24:1928–3192.

    Article  CAS  PubMed  Google Scholar 

  62. Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension. 2001;37:250–4.

    Article  CAS  PubMed  Google Scholar 

  63. Abramson EA, Arky RA, Woeber KA. Effects of propranolol on the hormonal and metabolic responses to insulin-induced hypoglycaemia. Lancet. 1996;24:21386–8.

    Google Scholar 

  64. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Antihypertensives and the risk of serious hypoglycemia in older persons using insulin or sulfonylureas. JAMA. 1997;278:40–3.

    Article  CAS  PubMed  Google Scholar 

  65. Deacon SP, Barnett D. Comparison of atenolol and propranolol during insulin-induced hypoglycaemia. Br Med J. 1976;2:272–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mills GA, Horn JR. Beta-blockers and glucose control. Drug Intell Clin Pharm. 1985;19:246–51.

    Article  CAS  PubMed  Google Scholar 

  67. Tfelt-Hansen P. The headaches: β-adrenoceptor blocking drugs in migraine prophylaxis. In: Olesen J, Goadsby P, Ramadan M, et al., editors. The Headaches. 3rd ed. Philadelphia: Lipincott, Williams & Wilkins; 2006.

    Google Scholar 

  68. Pascual J, Leira R, Lainez JM. Combined therapy for migraine prevention? Clinical experience with a β-blocker plus sodium valproate in 52 resistant migraine patients. Cephalalgia. 2003;23:961–2.

    Article  CAS  PubMed  Google Scholar 

  69. Pasqual J, Rivas MT, Leira R. Testing the combination beta-blockers plus topiramate in refractory migraine. Acta Neuro Scand. 2007;115:81–3.

    Article  Google Scholar 

  70. Silberstein SD, Dodick DW, Lindblad AS, Holroyd K, Harrington M, Mathew NT, et al. Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine. Neurology. 2012;78:976–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rao BS, Das DG, Taraknath VR, Sarma Y. A double blind controlled study of propranolol and cyproheptadine in migraine prophylaxis. Neurol India. 2000;48:223–6.

    CAS  PubMed  Google Scholar 

  72. Domingues RB, Silva AL, Domingues SA, et al. A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine. Arq Neuropsiquiatr. 2009;67:973–7.

    Article  PubMed  Google Scholar 

  73. Bordini CA, Arruda MA, Ciciarelli MC, Speciali JG. Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. A double-blind trial. Arq Neuropsiaquiatr. 1997;55:536–41.

    Article  CAS  Google Scholar 

  74. Yancey JR, Sheridan R, Koren KG. Chronic daily headache: diagnosis and management. Am Fam Physician. 2014;89:642–8.

    PubMed  Google Scholar 

  75. Palferman TG, Gibberd FB, Simmonds JP. Prophylactic propranolol in the treatment of headache. Br J Clin Pract. 1993;37:28–9.

    Google Scholar 

  76. Dodick DW. Chronic daily headaches. N Engl J Med. 2006;354:158–65.

    Article  CAS  PubMed  Google Scholar 

  77. Barron AJ, Zaman N, Cole G, et al. Systematic review of genuine versus spurious side-effects of bets-blockers in heart failure using placebo control. Recommendations for patient information. Int J Cardiol. 2013;163:3572–9.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Christopher H. Gottschalk MD.

Ethics declarations

Conflict of Interest

The authors declare that they have no 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

Danesh, A., Gottschalk, P.C.H. Beta-Blockers for Migraine Prevention: a Review Article. Curr Treat Options Neurol 21, 20 (2019). https://doi.org/10.1007/s11940-019-0556-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11940-019-0556-3

Keywords

Navigation