To investigate the factors affecting the efficacy and safety of verapamil for primary headache disorders using pharmacogenomic reports in electronic medical record (EMR).

Verapamil has a wide range of dosing in migraine and cluster headache. However, there is no reliable way to predict the effective and tolerable doses for an individual. Exploring the factors predicting the efficacy and safety of verapamil, especially with the emerging pharmacogenomic data in EMR, would be helpful to avoid the development of undesirable side effects.

This is a retrospective chart review study examining adults with a clinical pharmacogenomic report in EMR at Mayo Clinic who had used verapamil for primary headache disorders. We used Chi-square test, Kruskal Wallis analysis, and linear regression to identify the effect of demographic factors and phenotypes of six cytochromes P450(CYP) enzymes on the minimum effective and maximum tolerable verapamil doses for headache prevention.

74 patients met the inclusion criteria, and 33 of them had documented dosing and therapeutic responses were included in the final analysis. All used verapamil for migraine. The mean age was 51. The mean minimum effective and maximum tolerable doses were 178.2(20-320 mg) and 227.9(20-480 mg). CYP1A2 rapid, CYP2B6 intermediate, and CYP3A4 normal metabolizers were the predominant phenotypes within each group. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found; however, there was no significant difference in the minimum effective or maximum tolerable verapamil doses after adjusting for age, sex, BMI, and smoking status.

Although we did not identify any significance, we cannot exclude the effect of pharmacogenomic phenotypes on the effective and tolerable doses of verapamil. This study was limited by a small sample size, as pharmacogenomic testing is not routinely used in headache care. More studies examining the pharmacogenomic factors affecting the appropriate doses of headache preventive medications are needed to facilitate individualized medicine.