Serum Concentration Relationships of Candesartan in Migraine Prevention

Migraine is a common disabling disorder, and optimising affordable preventive treatments remains highly relevant. Candesartan is an effective and well-tolerated preventive treatment, but little is known about its dose-concentration-response relationships. We explored these relationships using data from the MigriNor study, a prospective observational cohort of adults with episodic or chronic migraine initiating oral preventive treatment. A total of 166 participants using candesartan were included (median age 35 years; 89% female). Participants completed a daily electronic headache diary during a 4-week baseline and 12-week follow-up period with accompanying blood sampling. Dosing regimen was flexible. No differences in adverse drug reactions (ADRs) or treatment acceptability were observed between participants starting 4 versus 8 mg. Substantial interindividual variability in serum concentrations was observed. Higher serum concentrations were associated with lower odds of headache attacks (OR = 0.97, 95% CI = 0.96-0.98, p < 0.001) and migraine attacks (OR = 0.98, 95% CI = 0.97-0.99, p = 0.005). Interquartile ranges of serum concentrations among ≥ 30% and ≥ 50% responders were 62.9-141.2 and 62.3-129.3 nmol/L, respectively, suggesting preliminary therapeutic reference ranges. Serum concentration was not associated with ADRs or treatment acceptability. Interpretation is limited by the flexible dosing design, and studies with fixed dosing regimens are warranted.