Candesartan Shown to be Safe, Effective as Option to Prevent Migraine in Adolescents

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Patients on candesartan saw statistically significant reductions in the mean frequency of monthly headache days, including moderate to severe headache days.

Irene Patniyot, MD

Findings from a small-scale retrospective chart review study provided evidence that candesartan, an antihypertensive drug, was well-tolerated and may be helpful in reduction of mean monthly headache days in adolescents with a high baseline headache frequency. Investigators concluded that patients may gain more benefit from the drug if used as a first-line treatment earlier in the disease course.

These findings were presented at the 2023 American Headache Society (AHS) Annual Meeting, held June 15-18, in Austin, Texas, by lead investigator Irene Patniyot, MD, director of the Pediatric Headache Clinic and Pediatric Headache Fellowship at Texas Children’s Hospital West Campus. Candesartan, an angiotensin receptor 2 blocker, has been typically used to treat high blood pressure and heart failure, but has also previously shown effectiveness for migraine prevention in randomized controlled trials.

Conducted between January 2016 and December 2022, the trial featured 24 complete records of adolescent patients followed at the Texas Children’s Hospital Headache Clinic. Patients had data on demographics, primary headache diagnosis, headache frequency in days per month prior to initiation and at first follow-up 2-6 months after initiation, frequency of moderate to severe headache days per week, number of preventive therapies being taken concurrently and tried prior to candesartan initiation, and reported adverse events.

Of the sample, chronic migraine was the most common diagnosis (54%), followed by new daily persistent headache (17%), episodic migraine (17%), and post-traumatic headache (12%). Mean monthly headache frequency, the primary outcome, was significantly reduced following treatment with candesartan, with patients experiencing an average of 23.3 days per month prior to initiation vs 19.6 days after (P = .04).

Following treatment, median headache days decreased from 30 (range, 3-30) to 19.5 (range, 0-30), with 5 individuals (21%) reporting at least a 50% reduction. Additionally, adolescents on the therapy saw statistically significant reductions in the mean frequency of moderate to severe headache days per week (pre-initiation: 3.3 days vs post-initiation: 2.6 days; P = .04). Investigators noted though that these data should be interpreted with caution because of subjective differences in patient reporting and note documentation. In terms of safety, Patniyot et al reported mild light-headedness and mild blood pressure decrease in 3 patients (12.5%).

In 2003, the first randomized, double-blind, controlled trial with a cross-over designed described that cardesartan was better than placebo in the reduction of days with headache over a 12-week period. The study included patients with 2-6 migraine attacks per month and prior use of more than 1 migraine preventive.² The only real-world evidence on candesartan for migraines came from a 2004 series case study of 8 patients with comorbid arterial hypertension that described improvement for both migraine and hypertension.

A 2019 retrospective cohort study further added evidence to the impact of candesartan on individuals with migraine. The trial featured 120 eligible patients, 70% (n = 84) of which had chronic migraine and 42.7% (n = 53) had medication-overuse headache. All told, treatment with the antihypertensive therapy resulted in at least a 50% response in 32.5% and 31.7% of patients at 3 and 6 months, respectively. The number of prior treatments (OR, 0.79; 95% CI, 0.64-0.97) and the presence of daily headache (OR, 0.39; 95% CI, 0.16-0.97) were associated with a lower probability of response.³

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REFERENCES
1. Patniyot I, Duggan D, Holick M, Dudley-harrell H. A retrospective analysis of the use of candesartan for migraine prevention in adolescents. Presented at: 2023 AHS Annual Meeting; June 15-18; Austin, TX. Abstract P-09.
2. Trovnik E, Stovner L, Helde J, et al. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289(1):65-69.
3. Sanchez-Rodriguez C, Sierra A, Planchuelo-Gomez A, et al. Real world effectiveness and tolerability of candesartan in the treatment of migraine: a retrospective cohort study. Scientific Reports. 2021;11:3846. doi:10.1038/s41598-021-83508-2