Another Drug for the Migraine Prophylaxis Armamentarium
Abstract & Commentary
Source: Tronvik E, et al. Prophylactic treatment of migraine with an angiotensin II receptor blocker. JAMA. 2003;289:65-69.
Several lines of evidence suggest that ACE inhibition and/or angiotensin receptor blockade can be effective for migraine prevention. Lisinopril has already been shown to reduce migraine headache.1 However, the excellent side-effect profile of the angiotensin receptor blockers (ARB) make them better candidates for this indication as these patients are either otherwise young and healthy and do not want drugs with side effects or they are already on many drugs and do not need any additional problems. Tronvik and colleagues report on the first well-designed trial of an ARB—candesartan for migraine prevention.
Sixty IHS-defined migraine patients aged 18-65 with 2-6 migraine attacks per month were enrolled in a randomized, double-blind, placebo-controlled crossover single-center study. A placebo run-in period of 4 weeks was followed by 2 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomized in each group to receive 16 mg of candesartan or placebo once per day. The primary end point was "the number of days with headache." In the ITT analysis (n = 57) for the 12-week period, the mean number of days with headache was 13.6 with candesartan vs 18.5 in the placebo group (P = 0.001). Most of the secondary end points also favored the candesartan group, such as days with migraine (12.6 vs 9.0; P < .001), headache severity index (293 vs 191; P < .001), and disability level (20.6 vs 14.1; P < .001). There was no difference between either group with respect to quality of life as measured on the Short Form 36 questionnaire. For each efficacy outcome, a "responder" was recorded when a symptom reduction of at least 50% was observed in the treatment group compared to placebo in accordance with IHS guidelines. As such in the candesartan group 18/57 (31.6%) had a > 50% reduction in "days with headache" and 23/57 (40.4%) for "days with migraine" compared to 1/57 (1.8%) and 2/57 (3.5%) in the placebo group (P = .001). Adverse events were similar in both groups.
Commentary
Aside from the small study size, several positive points can be made. First, the candesartan responder rates for headache and migraine days compares favorably with the published outcomes for several of the established migraine prophylactic drugs, such as propranolol and valproate, which are within the 30-40% range. Second, the small sample size most likely accounts for inability to demonstrate an advantage on quality-of-life measures in the candesartan group. Third, the lack of adverse effects and the overwhelming high tolerance of candesartan makes not only this drug but the whole class of ARBs a compelling new option for migraine prophylaxis. There is no effect on hemodynamics, no sexual dysfunction, no anticholinergic effects, no weight gain, nor is there a contraindication to asthma or diabetes, to name just a few of the advantages. One can only speculate as to the mechanism of action. Tronvik et al suggest several possibilities, including direct vasoconstriction, increased sympathetic discharge, and actions on angiotensin type I receptors within the brain itself. But virtually all of the present-day migraine preventatives lack an understanding of mechanism, and instead, we rely on the empiric evidence such as we have. — Jeffrey Reich
Dr. Reich is Assistant Professor Neurology, Movement Disorders Division, Columbia-Presbyterian Medical Center.
Reference
1. Schrader H, et al. BMJ. 2001;322:19-22.
Several lines of evidence suggest that ace inhibition and/or angiotensin receptor blockade can be effective for migraine prevention. Lisinopril has already been shown to reduce migraine headache.Subscribe Now for Access
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