TY - JOUR

T1 - The headache and aura-inducing effects of sildenafil in patients with migraine with aura

AU - Butt, Jawad H.

AU - S Eddelien, Heidi

AU - Kruuse, Christina

N1 - Publisher Copyright: © International Headache Society 2022.

PY - 2022

Y1 - 2022

N2 - Introduction: It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura. Methods: In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura. Results: Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher’s exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher’s exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks. Discussion: Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase. Trial registration: ClinicalTrials.gov – NCT02795351

AB - Introduction: It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura. Methods: In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura. Results: Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher’s exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher’s exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks. Discussion: Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase. Trial registration: ClinicalTrials.gov – NCT02795351

KW - Migraine with aura

KW - sildenafil, headache

U2 - 10.1177/03331024221088998

DO - 10.1177/03331024221088998

M3 - Journal article

C2 - 35332812

AN - SCOPUS:85127302348

VL - 42

SP - 984

EP - 992

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 10

ER -