Reproducibility of migraine-like attacks induced by phosphodiesterase-3-inhibitor cilostazol.

Introduction The phosphodiesterase-3-inhibitor cilostazol induces migraine-like attacks in patients with migraine without aura, and may be used as a pharmacological trigger in human experimental models of migraine. However, the reproducibility of cilostazol-induced migraine-like attacks has never been investigated. Methods We performed a post-hoc analysis of clinical data from two brain-imaging studies including subjects who had received cilostazol 200 mg orally. Only subjects who developed migraine-like attacks on study day 1 were included on study day 2. After cilostazol ingestion, subjects and the investigator recorded headache intensity and characteristics once every hour on a purpose-developed questionnaire. Primary end-points included incidence and time to onset of migraine-like attacks between two separate study days. Results Thirty-four subjects completed both experimental days and were included in this study. Thirty-four out of 34 subjects (100%) developed migraine-like attacks after cilostazol ingestion on both study days 1 and 2. Time to onset of migraine was five hours (range 1-8 hours) on study day 1 and four hours (range 1-8 hours) on study day 2, p = 0.16. We found no difference in median peak headache score, median time to peak headache score, or median time to intake of rescue medication between study days 1 and 2. Conclusion A second-time administration of cilostazol reproduces migraine-like attacks in all subjects who report an attack after their first cilostazol induction. There was no difference in time to migraine onset between separate inductions. Experimental migraine provocation using cilostazol is a highly efficient and useful approach for studying the ictal phase of migraine without aura.