Beta blockers, calcium channel blockers, and valproic acid have been used for migraine prophylaxis with varying degrees of success. One recent trial suggests that lisinopril is also efficacious. Tronvik and colleagues speculated that an angiotensin-II receptor blocker would be useful in migraine prophylaxis without the potential adverse effects of cough and angioedema that are often associated with angiotensin-converting enzyme inhibitors.

The authors designed a randomized, double-blind, crossover trial that included 60 patients from 18 to 65 years of age. The patients took placebo for a four-week run-in period, followed by two 12-week periods during which they received either placebo or candesartan. A four-week placebo washout period separated the active phases of the trial before crossover.

The primary outcome measured was number of days with headache. Secondary outcomes were hours with headache, days with migraine, hours with migraine, calculated headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, number of sick days, and health-related quality of life.

Fifty-seven patients participated in the primary analysis and 46 in the per-protocol analysis. Both analyses favored candesartan, with significant reduction in the primary outcome and the majority of secondary outcomes. Responders to candesartan, defined as those with a reduction of 50 percent or more in any one outcome measure, varied from 32 to 48 percent among candesartan users compared with 2 to 4 percent in placebo users.

The authors conclude that candesartan is comparable to other migraine prophylaxis medications, particularly beta blockers that showed in a meta-analysis a 33 percent improvement in headache index, similar to the effect of candesartan in this study. Because the adverse effects of candesartan were similar to those of placebo, the authors conclude that candesartan is an effective, well-tolerated migraine prophylactic agent.