Norwegian and Estonian researchers reported success in a phase II clinical trial of candesartan for migraine prevention. This antihypertensive drug significantly reduced the number of attack days compared to placebo. The study was published in The Lancet Neurology.
Migraine treatment includes both attack relief and prevention. Specific medications have been developed for prophylaxis, including monoclonal antibodies and low-molecular-weight CGRP receptor antagonists (gepants), but they are not effective for all patients and are not well tolerated by all. Moreover, according to scattered data, medications from various classes—antihypertensives, anticonvulsants, lipid-lowering medications, and antidepressants—may have varying prophylactic efficacy due to their pleiotropic effects, and they are often prescribed off-label for this indication. The true efficacy of most of these medications has not been adequately studied.
One such drug is the angiotensin AT1 receptor antagonist candesartan, which has been used to treat arterial hypotension for nearly 30 years. Observational studies and small clinical trials have shown it to be a potential migraine preventative.
Erling Tronvik of the Norwegian University of Science and Technology and colleagues conducted a phase II, triple-blind, randomized, controlled clinical trial, CandMig-3, at 10 clinical centers in Norway and Estonia. They enrolled 457 patients aged 18–64 years (mean 38.7 years; 86 percent women) experiencing two to eight episodic migraine attacks per month (with or without aura). They were randomly assigned in a 1:1:1 ratio to receive either placebo, 16 mg candesartan, or 8 mg candesartan daily for 12 weeks.
The mean number of migraine days per month at baseline was 5.7. By weeks 9–12, it had decreased by 2.04 with 16 milligrams of active drug (the low dose had similar efficacy) versus 0.82 with placebo: an absolute difference of -1.22 days (p < 0.0001). A reduction in attack frequency of 50 percent or more was achieved by 49 percent of patients in the main group versus 28 percent in the control group. The number of days requiring triptans (serotonin receptor agonists for the relief of migraine attacks) decreased by 1.3 and 0.4, respectively; however, there were no significant differences in the total duration of disability. Of the adverse events, dizziness was the most common, observed in 30 percent of participants in the main group and 13 percent in the control group. Serious adverse events occurred in three percent and one percent of participants, respectively, most of which were not treatment-related. Three percent of participants discontinued the trial early due to adverse events. Overall, candesartan was considered well-tolerated. These results provide evidence for the clinical utility of candesartan for migraine prophylaxis; however, further trials are needed to evaluate the long-term efficacy and safety in a wider range of patients. Previous population-based comparisons of the effectiveness of various migraine prophylaxis medications have shown that some older, inexpensive medications, such as simvastatin and amitriptyline, may be as effective as newer, more expensive ones.
