Tools for Practice


#52 Are antihypertensive medications effective for migraine prophylaxis?


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


BOTTOM LINE
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
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 (timololmetoprolol, atenolol, nadololacebutalol), calcium channel blockers (nimodipinenicardipine), 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 prophylaxis11,12 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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Author(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.