BACKGROUND: Cilostazol is an inhibitor of phosphodiesterase 3 and thus causes accumulation of cAMP. It induces migraine-like attacks in migraine patients. Whether the cilostazol model responds to sumatriptan in migraine patients and therefore is valid for testing of future anti-migraine medications has never been investigated.

METHODS: In a cross-over study, 30 patients received cilostazol (200 mg p.o.) on two separate days each day followed by oral self-administered placebo or sumatriptan 50 mg. We recorded headache characteristics and associated symptoms using a questionnaire. The 30 participants were asked to subsequently treat their spontaneous attacks with sumatriptan (50 mg) or placebo in a double-blind cross-over design and 15 participants did so.

RESULTS: Cilostazol induced headache with some migraine characteristics in all participants; 18 patients on the sumatriptan day and 19 patients on the placebo day fulfilled criteria for a migraine-like attack. The difference in median headache intensity between sumatriptan and placebo at 2 h was not significant (p = 0.09), but it was at 4 h (p = 0.017). During spontaneous attacks, the difference between placebo and sumatriptan was not significant at 2 h (p = 0.26), but it was highly significant at 4 h (p = 0.006).

CONCLUSION: The cilostazol model in migraine patients could not be validated by a sufficient sumatriptan response. The model may perhaps respond to new drugs that act intracellularly or directly on ion channels.

TRIAL REGISTRATION: The study is registered on clinicaltrials.gov ( NCT02486276 ).