Pain Free Efficacy of Sumatriptan in the Early Treatment of Migraine

Abstract

Migraine is a common neurological disorder that is characterized by episodic headaches associated with symptoms such as nausea, visual disturbances, photophobia, and phonophobia. In Canada, approximately 7% of adult males and 22% of adult females suffer from migraine. 1 Migraine symptoms result in a considerable burden with regard to health care utilization, health care costs, and work/productivity loss due to disability and decreased functional status. [2][3][4][5][6] Clinical trials have demonstrated that sumatriptan (Imitrex®, GlaxoSmithKline) is effective in relieving migraine pain. These studies have established the efficacy of sumatriptan among patients who treated their migraines at a point in which their headache pain was classified as moderate or severe. 7-11 However, ABSTRACT: Background: There is evidence that headache response rates may be higher if triptans are used early when a migraine attack is still mild, as compared to when it is treated after pain has reached moderate or severe intensity. Methods: In this randomized, double blind, placebo controlled, parallel group clinical trial, 361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a single attack study. The primary outcome measure was pain-free status at two hours. Results: In the intention to treat group, two hour pain free rates were 16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the sumatriptan 100 mg group respectively (p<0.001, active treatment groups vs. placebo). Conclusions: Both sumatriptan 50 mg and 100 mg were significantly superior to placebo for the pain-free end point at two hours. The pain-free response rates in this trial where sumatriptan was taken while the headache was still mild were generally higher than in older clinical trials where headache was treated after reaching a moderate or severe intensity. RÉSUMÉ: Absence de douleur comme mesure de l'efficacité du sumatriptan pour le traitement précoce de la migraine. Contexte: Le taux de réponse serait plus élevé si les triptans sont utilisés tôt au cours d'une crise de migraine alors que les symptômes sont légers plutôt que quand la douleur est devenue modérée ou sévère. Méthodes: Il s'agit d'une étude de pharmacologie clinique randomisée, à double insu, avec placebo et groupes parallèles. 361 patients ont pris soit le placebo, le sumatriptan 50 mg ou le sumatriptan 100 mg au cours d'une seule crise migraineuse. Le critère d'évaluation primaire était l'absence de douleur 2 heures après la prise du médicament. Résultats: À l'analyse selon l'intention de traitement, le taux de patients sans douleur était de 16%, 40% et 50% pour le groupe placebo, le groupe sumatriptan 50 mg et le groupe sumatriptan 100 mg respectivement (groupes traitement actif versus placebo, p > 0,001). Conclusions: Le sumatriptan 50 mg et 100 mg étaient significativement supérieurs au placebo quant au critère d'évaluation primaire, soit l'absence de douleur 2 heures après la prise du médicament. Le taux de réponse, soit l'absence de douleur, dans cette étude ...

DHE Repression of ATP‐Mediated Sensitization of Trigeminal Ganglion Neurons

“…To our knowledge, our study provides the first evidence that ATP can lower the activation threshold of trigeminal neurons to K+ ions and, hence, can function to promote peripheral sensitization of nociceptive afferent fibers that provide innervation of the meningeal blood vessels and are involved in the pain of migraine. Based on our findings, we propose that DHE, as has been reported for the triptans, may be most beneficial therapeutically if taken early in a migraine attack during the initial stages characterized by peripheral sensitization and when headache pain is mild 57‐59 . In addition, our results provide evidence that DHE should be most effective in treating migraine with aura as these types of attacks are characterized by CSD, an event that triggers increased release of ATP and K+ ions that can lead to activation of trigeminal nociceptive neurons.…”

“…Based on our findings, we propose that DHE, as has been reported for the triptans, may be most beneficial therapeutically if taken early in a migraine attack during the initial stages characterized by peripheral sensitization and when headache pain is mild. [57][58][59] In addition, our results provide evidence that DHE should be most effective in treating migraine with aura as these types of attacks are characterized by CSD, an event that triggers increased release of ATP and K+ ions that can lead to activation of trigeminal nociceptive neurons. It will be of interest to determine in clinical trials whether more rapid dosing of DHE, as reported for LEVADEX™, will be more beneficial in treating migraine with aura than migraine without aura and whether it will be more effective than triptans.…”

Are the current IHS guidelines for migraine drug trials being followed?

“…Several of the acute trials investigate the relationship between the timing of drug intake (in relation to the onset of migraine pain or cutaneous allodynia) and drug efficacy [23, 62, 73, 86, 102, 103, 122, 130]. The results of these trials suggest that “early” triptan administration, while the headache is mild, is more efficient in terms of pain-free outcomes and reduced risk of recurrence when compared to “late” administration, when the headache is moderate to severe.…”

The Migraine Intervention Score - a tool to improve efficacy of triptans in acute migraine therapy: the ALADIN study

“…Patients with very frequent attacks also need to be careful about rapid self-treatment with acute medication so that the maximum monthly dosage is not exceeded. The advantages of early treatment include greater and more rapid efficacy (9,11,13,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). In addition, cutaneous allodynia may develop over the course of the attack, reducing the efficacy of triptans.…”

“…Recent randomised, double-blinded, placebo-controlled clinical trials have examined the early use of triptans for therapy of migraine headaches (13,25,26,29,32,(40)(41)(42)(43). In addition, a number of open-label or unblinded studies have been published that show the benefits of treatment during the early phases of a migraine attack (9,11,19,20,22,28,32). The 'Act when Mild' study, performed under carefully controlled conditions with a rigorous study design, showed that improved efficacy could be achieved when attacks were treated within the first hour of an attack or when pain intensity was mild (13).…”