ACE and ARB Agents in the Prophylactic Therapy of Migraine—How Effective Are They?

  • Rashmi B. Halker
  • Amaal J. Starling
  • Bert B. Vargas
  • Todd J. SchwedtEmail author
Headache (JR Couch, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Headache

Opinion statement

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are antihypertensive agents that can be considered for migraine preventative therapy. Although the exact mechanisms by which ACE inhibitors and ARBs may work for migraine prophylaxis are unknown, there are several plausible hypotheses as to why modulating the activity of the renin angiotensin system could result in migraine prevention. Clinical trials of ACE inhibitors and ARBs provide evidence that they are effective and generally well tolerated when used for migraine prophylaxis. Based upon biologic plausibility, the quality of evidence for efficacy from clinical trials, and recommendations in published guidelines, we consider ACE inhibitors and ARBs as second- or third-line options for migraine prophylaxis.


Migraine Headache Angiotensin converting enzyme inhibitors Angiotensin receptor blockers 


Compliance with Ethical Standards

Conflict of Interest

Rashmi B. Halker M.D., Amaal J. Starling M.D., and Bert B. Vargas declare that they have no conflict of interest.

Todd J. Schwedt has received personal fees from Supernus, Allergan, and Zogenix.

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.

References and Recommended Reading

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

  1. 1.
    Lipton RB et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Munakata J et al. Economic burden of transformed migraine: results from the American migraine prevalence and prevention (AMPP) study. Headache. 2009;49(4):498–508.CrossRefPubMedGoogle Scholar
  3. 3.
    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 123–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Paterna S et al. Captopril versus placebo in the prevention of hemicrania without aura. A randomized double-blind study. Clin Ter. 1992;141(12):475–81.PubMedGoogle Scholar
  5. 5.
    Schrader H et al. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (Lisinopril): randomised, placebo controlled, crossover study. BMJ. 2001;322(7277):19–22.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.•
    Sonbolestan SA et al. Efficacy of enalapril in migraine prophylaxis: a randomized, double-blind, placebo-controlled trial. Int J Prev Med. 2013;4(1):72–7. This is a recent randomized placebo-controlled trial of an ACE inhibitor for the preventative treatment of migraine.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Jackson JL et al. A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PLoS ONE. 2015;10(7):e0130733.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Shamliyan TA, Kane RL, and Taylor FR. In Migraine in adults: preventive pharmacologic treatments 2013: Rockville (MD).Google Scholar
  9. 9.••
    Silberstein SD et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the quality standards subcommittee of the American academy of neurology and the American headache society. Neurology. 2012;78(17):1337–45. These are evidence-based guidelines on the preventative treatment of migraine from the American Academy of Neurology and the American Headache Society.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.••
    Pringsheim T et al. Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2):S1–59. These are evidence-based guidelines on the preventative treatment of migraine from the Canadian Headache Society.PubMedGoogle Scholar
  11. 11.
    Tronvik E et al. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289(1):65–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Diener HC et al. Telmisartan in migraine prophylaxis: a randomized, placebo-controlled trial. Cephalalgia. 2009;29(9):921–7.CrossRefPubMedGoogle Scholar
  13. 13.•
    Stovner LJ et al. A comparative study of candesartan versus propranolol for migraine prophylaxis: a randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2013;34(7):523–32. This is a recent randomized controlled trial of an ARB for the preventative treatment of migraine.CrossRefPubMedGoogle Scholar
  14. 14.
    Marques-Lopes J et al. Microinjection of angiotensin II in the caudal ventrolateral medulla induces hyperalgesia. Neuroscience. 2009;158(4):1301–10.CrossRefPubMedGoogle Scholar
  15. 15.
    Onder G et al. Association between ACE inhibitors use and headache caused by nitrates among hypertensive patients: results from the Italian group of pharmacoepidemiology in the elderly (GIFA). Cephalalgia. 2003;23(9):901–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Reuter U et al. Nuclear factor-kappaB as a molecular target for migraine therapy. Ann Neurol. 2002;51(4):507–16.CrossRefPubMedGoogle Scholar
  17. 17.
    Lorenzo O et al. Angiotensin III activates nuclear transcription factor-kappaB in cultured mesangial cells mainly via AT(2) receptors: studies with AT(1) receptor-knockout mice. J Am Soc Nephrol. 2002;13(5):1162–71.PubMedGoogle Scholar
  18. 18.
    Iwai M et al. Attenuation of focal brain ischemia by Telmisartan, an angiotensin II type 1 receptor blocker, in atherosclerotic apolipoprotein E-deficient mice. Hypertens Res. 2008;31(1):161–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Horasanli B et al. Angiotensin I-converting enzyme gene (I/D) polymorphism in patients with migraine. Headache. 2013;53(1):161–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Kowa H et al. Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura. Neurosci Lett. 2005;374(2):129–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Paterna S et al. Angiotensin-converting enzyme gene deletion polymorphism determines an increase in frequency of migraine attacks in patients suffering from migraine without aura. Eur Neurol. 2000;43(3):133–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Lewandowski J et al. The effect of enalapril and Telmisartan on clinical and biochemical indices of sympathetic activity in hypertensive patients. Clin Exp Hypertens. 2008;30(5):423–32.CrossRefPubMedGoogle Scholar
  23. 23.•
    Tronvik E et al. Involvement of the renin-angiotensin system in migraine. J Hypertens Suppl. 2006;24(1):S139–43. This is a narrative review on how the renin-angiotensin system can play a role in migraine pathophysiology.CrossRefPubMedGoogle Scholar
  24. 24.
    Shamliyan TA et al. Preventive pharmacologic treatments for episodic migraine in adults. J Gen Intern Med. 2013;28(9):1225–37.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gales BJ et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the prevention of migraines. Ann Pharmacother. 2010;44(2):360–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Rashmi B. Halker
    • 1
  • Amaal J. Starling
    • 1
  • Bert B. Vargas
    • 1
  • Todd J. Schwedt
    • 1
    Email author
  1. 1.Department of NeurologyMayo ClinicPhoenixUSA

Personalised recommendations