Pre-treatment with sumatriptan for cilostazol induced headache in healthy volunteers

Abstract

Background: Previous studies indicate that sumatriptan is not effective when second messenger levels are high as after cilostazol provocation. Therefore, we have conducted the present study, where sumatriptan is administrated as pretreatment before cAMP increases due to cilostazol intake. Our hypothesis was that pretreatment with sumatriptan would have a significant effect against cilostazol induced headache in healthy volunteers.

Methods: In a double-blind, randomized, crossover design, 30 healthy volunteers of both sexes received cilostazol 200 mg on two separate days, each day preceded by oral sumatriptan (2 × 50 mg) or placebo. Headache response and accompanying symptoms were registered in a questionnaire by the participants themselves.

Results: Cilostazol induced a mild to moderate headache in all but 3 participants (Range 0-7 on Numerical Rating Scale). There was no significant difference in headache score 2 h (p = 0.67) or 4 h (p = 0.1) after treatment between the 2 days. Median peak headache score was 1.5 (range 0-5) on the sumatriptan day and 2 (range 0-7) on the placebo day (p = 0.26).

Conclusion: Pre-treatment with sumatriptan prevents cilostazol induced headache from developing. However, the placebo group did not develop enough headache to get statistical significant results. The cilostazol pre-treatment model is valuable for experimental headache research and perhaps for testing drugs with another mechanism of action.

Trial registration: ClinicalTrials.gov Identifier: NCT03156920 .

Keywords: Headache; Human migraine model; Migraine; Pain; Phosphodiesterase type 3.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Copenhagen (H-15011960). All participants received oral and written information and provided written informed consent before inclusion in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Headache score 0-12 h after cilostazol. Median headache score 0-12 h after cilostazol. Median headache score was 1 on both days and thus we found no difference between the two treatment days

Fig. 2

Headache score after treatment. Headache score 0 h, 2 h and 4 h after treatment with placebo and sumatriptan. There was no difference in headache score at any time-point between the two treatment days

Fig. 3

Peak headache score. Difference in median peak headache score on the two treatment days was not statistical significant