BACKGROUND: A group of neurologists noted a significant improvement in migraine frequency after one of their patients began taking lisinopril for hypertension. ACE inhibitors’ effects on sympathetic activity, decreased free radicals, and increased prostacyclin may explain its role in decreasing migraine headache. Additionally, recent genetic studies have found that migraine without aura is more common in people with a certain genotype for ACE.
POPULATION STUDIED: Sixty adult patients with migraine headache occurring 2 to 6 times per month were recruited from an outpatient neurology clinic and with advertisements. The study presents complete data for 38 women (mean age=41 years) and 9 men (mean age=43 years). Standard criteria for the definition of migraine were used. Patients were excluded if they had nonmigraine headaches that could not be distinguished from migraine, used other prophylactic medications, were pregnant or unable to use contraceptives, had impaired hepatic or renal function, or had a history of hypersensitivity to ACE inhibitors. The study cohort likely represents migraine sufferers at the more severe end of the spectrum seen by primary care physicians.
STUDY DESIGN AND VALIDITY: The participants entered a double-blind placebo-controlled crossover study. There was a 12-week treatment period: The dose of lisinopril was 10 mg for 1 week, then 20 mg for the remaining 11 weeks. After this initial period, patients receiving lisinopril were switched to placebo for 12 weeks and vice versa. The participants kept a daily diary of headache symptoms, medication use, sick leave use, and quality-of-life measures.
OUTCOMES MEASURED: The primary outcome measures were the number of hours and days with headache and the number of days with migraine. The secondary outcomes were the headache severity index, use of medications for symptomatic relief, quality of life, number of sick-leave days taken, and the acceptability of treatment.
RESULTS: Sixty patients were randomized, and 55 were included in an intention-to-treat analysis (including 8 patients who did not comply properly with the protocol). Hours with headache decreased from 162 to 138 in the lisinopril group, with a mean reduction of 15% (95% confidence interval [CI], 0-30). Days with headache and days with migraine were also reduced by 16% (95% CI, 5-27) and 22% (95% CI, 11-33), respectively. Fourteen participants (25%) had a 50% decrease in the number of days with headache.
This well-designed study of lisinopril for moderate migraine sufferers suggests that another class of medications may be beneficial for prophylaxis. Though a relatively modest decrease in headaches was reported and there was wide variability in the results, lisinopril was well tolerated and has advantages over current prophylactic medications. A certain subset of patients responded very well to treatment. For patients with frequent migraines who have not responded to other prophylactic medications, a trial of ACE inhibitors may be useful.