Introduction

Migraine affects about 240 million people, worldwide, and is extremely disabling. There are newer drugs that can prevent attacks - the triptans - but often they provide only partial relief.

The angiotensin-converting enzyme (ACE) inhibitors lower blood pressure very effectively. One of them, lisinopril, has been shown to be effective in preventing migraine attacks. It's not surprising, therefore, that scientists have tested a closely related type of drug, an angiotensin II receptor blocker (ARB), to see if this class of drugs could have the same protective effect. They reported the results of their study in the Journal of the American Medical Association.

What was done

This study was done at a neurological outpatient clinic in Norway. Participants were recruited by newspaper advertisements. To be included, they had to have 2 to 6 migraine attacks a month for at least a year.

All the participants were given an inactive tablet (a 'placebo') for 4 weeks, to check the frequency of migraines. They were then distributed at random to take the ARB, (candesartan), or a matching placebo. After 12 weeks, the participants were taken off medication for 4 weeks, to allow any drug to be completely washed out of their system. Then they switched to take the alternative medication - placebo or candesartan - for another 12 weeks.

The participants kept 'headache diaries', with details of the duration and severity of headaches, how disabling they were, and if they were accompanied by nausea, vomiting, etc. The medications taken, the days of sick leave, and any side effects of the medication were also recorded.

The chief measure of a protective effect was decided, in advance, to be the number of days with headache; secondary measures included the number of hours with headache, the severity of headache, the level of disability, and doses of triptans and painkillers.

What was found

Sixty people started the treatment - either candesartan or placebo - and 57 completed the final switched medication period. In the final analysis, there were 45 women and 12 men.

In the 12-week treatment periods, the average number of days with headache was 18.5 with placebo, compared with only 13.6 with candesartan; this difference was considered significant. The number of hours with headache, the severity of headache, and disability levels were all significantly reduced by candesartan, compared with placebo. The differences in favor of candesartan ranged from 26% to 36%.

Average blood pressures during the treatment periods were significantly lowered by candesartan. There were no differences in the side effects reported during the candesartan and placebo treatment periods.

Comment

Other types of blood pressure drugs have been found to prevent migraine attacks - beta-blockers, calcium channel blockers, and, more recently, ACE inhibitors. The anti-seizure medication valproic acid is another drug that works. It's tempting to suggest there's a connection between the effectiveness of ACE inhibitors and the ARB tested in this study, but it may not be anything so obvious. It's more likely that factors other than angiotensin play a role. Until more is known, we can add the ARB candesartan to the growing list of medications that may be used with hope of success in preventing migraine attacks.