JAMA Vol. 289 No. 1, January 1, 2003


Prophylactic Treatment of Migraine With an Angiotensin II Receptor Blocker

A Randomized Controlled Trial

Erling Tronvik, MD; Lars J. Stovner, PhD; Grethe Helde, RN; Trond Sand, PhD; Gunnar Bovim, PhD

JAMA. 2003;289:65-69.

Context There is a paucity of effective, well-tolerated drugs available for migraine prophylaxis.

Objective To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug.

Design and Setting Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002.

Patients Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements.

Interventions A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan.

Main Outcome Measures The primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire.

Results In a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (P = .001) in the intention-to-treat analysis (n = 57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95; P<.001), days with migraine (12.6 vs 9.0; P<.001), hours with migraine (92.2 vs 59.4; P<.001), headache severity index (293 vs 191; P<.001), level of disability (20.6 vs 14.1; P<.001) and days of sick leave (3.9 vs 1.4; P = .01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of 50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods.

Conclusion In this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.


Author Affiliations: Department of Neurology and Clinical Neurophysiology, Norwegian University of Science and Technology, Trondheim, Norway.




Angiotensin-Receptor Blockade to Prevent Migraines
Journal Watch (General) 2003;2003:7-7.
FULL TEXT

 

Journal Watch online

January 2003

Summary and Comment
Angiotensin-Receptor Blockade to Prevent Migraines
Recently, the angiotensin-converting-enzyme (ACE) inhibitor lisinopril was shown to have some activity in migraine prevention (Journal Watch Feb 9 2001); thus, industry-sponsored researchers sought to determine whether an angiotensin-receptor blocker (ARB) also might be effective.

In a randomized, double-blind, crossover study from Norway, 60 migraine patients were assigned to receive either the ARB candesartan (16 mg daily) or placebo for 12 weeks, and, then, the opposite treatment for 12 weeks. Although patients improved during both their candesartan and placebo phases, improvements were significantly greater with candesartan than with placebo for several endpoints. For example, the mean number of headache days per month dropped from 8.4 at baseline to 6.2 during the placebo phase and to 4.6 during the candesartan phase. A 50% reduction in headache days occurred in 32% of patients during candesartan therapy but in only 2% of patients during placebo therapy. Mean systolic blood pressure was significantly lower with candesartan than with placebo (115 vs. 126 mm Hg), but the incidence of adverse events did not differ significantly between treatment phases.

Comment: Numerous drugs, including ß-blockers, valproic acid, and amitriptyline, have proven efficacy for preventing migraine headaches. ACE inhibitors and ARBs appear to be reasonable alternatives, with few side effects. Unfortunately, no single agent is predictably effective and well tolerated in all migraine sufferers. Acute and preventive drug therapies for migraine were reviewed recently in a practice guideline from the American Academy of Neurology (Neurology 2000; 55:754).

— Allan S. Brett, MD

Published in Journal Watch January 24, 2003

Source

Tronvik E et al. Prophylactic treatment of migraine with an angiotensin II receptor blocker: A randomized controlled trial. JAMA 2003 Jan 1; 289:65-9.

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