TY - JOUR

T1 - Cilostazol induced migraine does not respond to sumatriptan in a double blind trial

AU - Falkenberg, Katrine

AU - Dunga, Bára Óladóttir Á

AU - Guo, Song

AU - Ashina, Messoud

AU - Olesen, Jes

PY - 2018

Y1 - 2018

N2 - 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 ).

AB - 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 ).

KW - Adult

KW - Cilostazol

KW - Cross-Over Studies

KW - Cyclic AMP

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Migraine Disorders/chemically induced

KW - Models, Neurological

KW - Phosphodiesterase 3 Inhibitors/adverse effects

KW - Serotonin 5-HT1 Receptor Agonists/therapeutic use

KW - Sumatriptan/therapeutic use

KW - Surveys and Questionnaires

KW - Tetrazoles/adverse effects

KW - Treatment Failure

KW - Young Adult

U2 - 10.1186/s10194-018-0841-7

DO - 10.1186/s10194-018-0841-7

M3 - Journal article

C2 - 29396788

VL - 19

JO - Journal of Headache and Pain

JF - Journal of Headache and Pain

SN - 1129-2369

M1 - 11

ER -