#52 Are antihypertensive medications effective for migraine prophylaxis?

CLINICAL QUESTION

QUESTION CLINIQUE

In patients with frequent and/or severe migraines, are antihypertensive medications effective in reducing frequency or severity of migraines?

BOTTOM LINE

RÉSULTAT FINAL

A number of antihypertensive medications are effective in migraine prophylaxis. The best data are for propranolol, which will benefit one in four patients (over placebo).

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EVIDENCE

DONNÉES PROBANTES

Systematic review of propranolol for migraine prophylaxis, 58 trials (5,072 patients).¹

Versus Placebo: Propranolol statistically significantly:
- Improved migraine control: For example, more patients on propranolol attained a 50% reduction in headaches (57.1% versus 29.7%), Number Needed to Treat (NNT)=4.
- Increased drop-out due to adverse events (4.1% versus 1.6%), Number Needed to Harm 40.
Versus other medications (primarily other beta-blockers & calcium channel blockers): No consistent differences.
- Low quality studies and heterogeneity make definitive statements difficult.
- Recent industry-sponsored cross-over trial of 54 patients found candesartan was not inferior to propranolol.²

Randomized Controlled Trial (RCT) with 55 patients on lisinopril 20 mg/day or placebo:³

Statistically significant reduction in headache frequency: 7.9 days/month on placebo versus 6.6 days/month on lisinopril.
Rescue medications and headache severity also reduced.

RCT with 57 patients on candesartan 16 mg/day or placebo for migraine prophylaxis:⁴

Statistically significant reduction in headache frequency: 6.2 days/month on placebo versus 4.5 days/month on candesartan.
Rescue medications and sick leave days also reduced.

Reviews of verapamil, although low quality, suggest it too improves headache.^5,6 Recent systematic review found other beta-blockers (timolol, metoprolol, atenolol, nadolol, acebutalol), calcium channel blockers (nimodipine, nicardipine), captopril, candesartan, and clonidine all improve some measures of migraine frequency/severity, although evidence is limited and not all effects consistent.^7,8 Recent small study from Iran suggests enalapril may also be effective.⁹ Context:

Meta-analysis of 95 hypertension RCTs (24,244 participants) reporting headache among the adverse events:¹⁰
- Patients taking any of the four classes of antihypertensives (thiazides, beta-blockers, ACE inhibitors, or ARBs) reported headache less often than those taking placebo.
Two reviews of migraine prophylaxis^11,12 suggest the following antihypertensives (with starting doses¹²): Propranolol (20 mg BID) is consistently highly recommended,^11,12 followed by nadolol (80 mg OD),¹² metoprolol,¹¹ lisinopril (20 mg),^11,12 candesartan (16 mg),^11,12 or verapamil (40mg TID).11,12 Similar recommendations are found in Canadian and US guidelines.^13,14
Anticonvulsants and Tricyclic anti-depressants are also effective.¹⁵

updated may 11 2015 by adrienne

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September 19, 2011

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Author(s)

Auteur(s)

G. Michael Allan MD CCFP
Michael J Kapusta BSc (medical student)

1. Linde K, Rossnagel K. Cochrane Database Syst Rev. 2004; 2:CD003225.

2. Stovner LJ, Linde M, Gravdahl GB, et al. Cephalalgia. 2014; 34(7):523-32.

3. Schrader H, Stovner LJ, Helde G, et al. BMJ. 2001; 322:10-22.

4. Tronvik E, Stovner LJ, Helde G, et al. JAMA. 2003; 289(1):65-9.

5. Markley HG. Am J Med. 1991; 90(5):S48-S53.

6. Solomon GD. Headache. 1989 Jul; 29(7):425-7.

7. Shamliyan TA, Kane RL, Taylor FR. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Apr. Report No.: 13-EHC068-EF.

8. Shamliyan TA, Choi JY, Ramakrishnan R, et al. J Gen Intern Med. 2013 Sep; 28(9):1225-37.

9. Sonbolestan SA, Heshmat K, Javanmard SH, et al. Int J Prev Med. 2013; 4:72-7.

10. Law M, Morris JK, Jordan R, et al. Circulation. 2005; 112:2301-6.

11. Fenstermacher N, Levin M, Ward T. BMJ. 2011; 342:d583.

12. Pringsheim T, Davenport WJ, Becker WJ. CMAJ. 2010; 182(7):E269-E276.

13. Pringsheim T, Davenport W, Mackie G, et al. Can J Neurol Sci. 2012; 39(2 suppl 2):S1-59.

14. Silberstein SD, Holland S, Freitag F, et al. Neurology. 2012; 78:1337-45.

15. Allan GM, Levy M. Tools for Practice #51. Available at http://www.acfp.ca/wp-content/uploads/tools-for-practice/1397836024_20111028_100921.pdf. Accessed May 11, 2015.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.