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

Abstract

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

Investigations of the migraine-provoking effect of levcromakalim in patients with migraine with aura

“…Despite our methodology's consistency with past research, the results contrast with earlier findings, suggesting possible limitations in statistical power or an overestimation of effect size in our initial studies. A notable aspect of our study is the unexpectedly high nocebo response rate for migraine aura (7.4%), contrasting with earlier studies where no aura symptoms were reported post-placebo (8,13,14). Interestingly, one of the two participants reporting aura following placebo reported that the aura did not mimic spontaneous attacks.…”

Chronic Pain and Erectile Dysfunction: Mechanism, Treatment, and Future Perspective

“…Then sildenafil 50mg was replaced with lowdose vardenafil 5mg. 5 days after that, complaints of cluster headaches improved with ED symptoms (55). The incidence of pain after intracavernous injection is also high.…”

Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis

“…Headache and migraine are common side effects of PDE5Is, though the pathophysiologic mechanism remains unclear. 34 , 35 These side effects may be related to psychiatric disorders such as depression and anxiety that often accompany ED and are associated with headaches. In this study, headache and migraine were reported frequently for only vardenafil and avanafil with no signals detected.…”