Skip to main content

Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the Preventative Treatment of Episodic Migraine in Adults


Purpose of Review

Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with migraine. To identify gaps in research and provide guidance for future clinical trials.

Recent Findings

A search was completed using PubMed, MEDLINE, Embase, and the Cochrane Library January 1, 1990 through December 31, 2017. The following are keywords used in the search: migraine, migraine prophylaxis/prevention, renin-angiotensin-aldosterone system, RAAS, ACE inhibitors, angiotensin-converting enzyme inhibitors: quinapril, perindopril, ramipril, captopril, enalapril, lisinopril, benazepril, fosinopril. Angiotensin receptor blockers, ARB, angiotensin II receptor antagonists: candesartan cilexetil, irbesartan, olmesartan, valsartan, losartan, azilsartan medoxomil, telmisartan, and eprosartan. The search included randomized controlled trials (RCT), systemic reviews and open-label studies of ACE inhibitors and ARB for the prevention of migraine attacks in adults 18–70 years old. Of 2461 retrieved articles, 18 included RCT, meta-analysis, systemic reviews, or guidelines published on ACE inhibitors or ARB in the prevention of migraine. Three RCT with telmisartan 80 mg, candesartan 16 mg, and enalapril 10 mg, and two open-label trials with lisinopril 5 mg and ramipril 5 mg found a high number of responders with greater than 50 % reduction in migraine attack frequency when compared to a 4-week baseline period. Candesartan was superior to placebo while telmisartan and enalapril were not.


Lipophilic ACE inhibitors and ARBs can be effective prophylactic agents for reduction of migraine frequency in adults. Based on the limited number of published trials and small sample size, they are not recommended as first-line prophylactic agents. However, in populations with co-morbidities such as hypertension, they may be useful as first- or second-line prophylactics. Additional trials following the International Headache Society’s guidelines on RCT are warranted.

This is a preview of subscription content, access via your institution.


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

  1. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache: The Journal of Head and Face Pain. 2013;53(3):427–36.

    Article  Google Scholar 

  2. Raval AD, Shah A. National trends in direct health care expenditures among US adults with migraine: 2004 to 2013. J Pain. 2017;18(1):96–107.

    Article  Google Scholar 

  3. Rapoport AM. Acute and prophylactic treatments for migraine: present and future. Neurol Sci. 2008;29(1):110–22.

    Article  Google Scholar 

  4. Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton R, Pascual J, et al. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia. 2008;28(5):484–95.

    Article  CAS  Google Scholar 

  5. Nandha R, Singh H. Renin angiotensin system: a novel target for migraine prophylaxis. Indian J Pharm. 2012;44(2):157.

    Article  CAS  Google Scholar 

  6. Galletti F, Cupini LM, Corbelli I, Calabresi P, Sarchielli P. Pathophysiological basis of migraine prophylaxis. Prog Neurobiol. 2009;89(2):176–92.

    Article  CAS  Google Scholar 

  7. Burnier M. Telmisartan: a different angiotensin II receptor blocker protecting a different population? J Int Med Res. 2009;37(6):1662–79.

    Article  CAS  Google Scholar 

  8. Pringsheim T, Davenport WJ, Becker WJ. Prophylaxis of migraine headache. Cmaj. 2010;182(7):E269–E276. Epub 2010/02/18.

    Article  Google Scholar 

  9. U.S. Preventive Services Task Force. Guildeline to clinical preventive services. Baltimore. p. 1989.

  10. Stovner LJ, Linde M, Gravdahl GB, Tronvik E, Aamodt AH, Sand T, et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: a randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2014;34(7):523–32.

    Article  Google Scholar 

  11. Diener H, Gendolla A, Fruersenger A, Evers S, Straube A, Schumacher H, et al. Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial. Cephalalgia. 2009;29(9):921–7.

    Article  CAS  Google Scholar 

  12. Sonbolestan SA, Heshmat K, Javanmard SH, Saadatnia M. Efficacy of enalapril in migraine prophylaxis: a randomized, double-blind, placebo-controlled trial. Int J Prev Med. 2013;4(1):72.

    PubMed  PubMed Central  Google Scholar 

  13. 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 : J Am Med Assoc. 2003;289(1):65–9.

    Article  CAS  Google Scholar 

  14. Park H-J, Lee S-T, Kim M. Inhibitory control of angiotensin-converting enzyme by ramipril in migraine. Neurology Asia. 2013;18(3):289–91.

    Google Scholar 

  15. 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(6):701–3.

    Article  CAS  Google Scholar 

  16. Pringsheim T, Davenport W, Mackie G, Worthington I, Aubé M, Christie SN, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2):S1–59.

    PubMed  Google Scholar 

  17. Shamliyan TA, Choi J-Y, Ramakrishnan R, Miller JB, Wang S-Y, Taylor FR, et al. Preventive pharmacologic treatments for episodic migraine in adults. J Gen Intern Med. 2013;28(9):1225–37.

    Article  Google Scholar 

  18. • Ikeda K, Hanashiro S, Ishikawa Y, Sawada M, Kyuzen M, Morioka H, et al. Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine. Neurol Sci. 2017;38(5):827–31 This manuscript demonstrates the efficacy of telmisartan for the treatment of migraines.

    Article  Google Scholar 

  19. Barbanti P, Aurilia C, Egeo G, Fofi L. Migraine prophylaxis: what is new and what we need? Neurol Sci. 2011;32(1):111.

    Article  Google Scholar 

  20. Lipton RB, Manack Adams A, Buse DC, Fanning KM, Reed ML. A comparison of the chronic migraine epidemiology and outcomes (CaMEO) study and American migraine prevalence and prevention (AMPP) study: demographics and headache-related disability. Headache: The Journal of Head and Face Pain. 2016;56(8):1280–9.

    Article  Google Scholar 

  21. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ. What is “quality of evidence” and why is it important to clinicians? BMJ (Clinical research ed). 2008;336(7651):995–8.

    Article  Google Scholar 

  22. Moschiano F, D’Amico D, Bussone G. Migraine prophylaxis: key points for the practising clinician. Neurol Sci. 2009;30(1):33–7.

    Article  Google Scholar 

  23. • Halker RB, Starling AJ, Vargas BB, Schwedt TJ. ACE and ARB agents in the prophylactic therapy of migraine-how effective are they? Curr Treat Options Neurol. 2016;18(4):15 This paper provides evidence based on clinical trials that ACE inhibitors and ARBs are effective and generally well tolerated when used for migraine prophylaxis.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to C. A. Ganzer.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

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.

All authors contributed equally to this work.

This article is part of the Topical Collection on Episodic Migraine

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dorosch, T., Ganzer, C.A., Lin, M. et al. Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in the Preventative Treatment of Episodic Migraine in Adults. Curr Pain Headache Rep 23, 85 (2019).

Download citation

  • Published:

  • DOI:


  • Angiotensin-converting enzyme inhibitors
  • Angiotensin receptor blockers
  • Headache
  • Migraine