Emerging acute treatments for migraine

Over the last decade new drugs have become available for both acute and preventive migraine treatments. The development of two new triptans, frovatriptan and eletriptan, a nasal formulation of zolmitriptan, and the butyrophenone neuroleptic droperidol, have been shown to be effective in the acute treatment of migraine headache and associated symptoms.

Recent research into the pathophysiology of migraine has demonstrated that migraine is a neurovascular disorder with a central nervous system generator. As a result of these new findings, the direction of migraine management has switched form targetting intracranial vascular tone to attempting to modulate neurotransmitter systems.Emerging treatments for acute migraine include the development of two new triptans (frovatriptan and eletriptan), a nasal formulation of zolmitriptan, and the butyrophenone neuroleptic droperidol.Eletriptan is a new first-line triptan that has been shown to be safe and effective for acute migraine treatment. It is highly lipophilic and is therefore rapidly absorbed and displays a shorter Tmax (1hour) compared with sumatriptan (2-3hours). It is also about three times more bioavailable than sumatriptan. Eletriptan has a relatively long plasma half-life of 4hours and slowly dissociated from it’s receptor, which may explain its high efficacy and sustained effect in the treatment of migraine. The most common adverse effects of eletriptan are asthenia, paresthesias, dizziness, nausea and drowsiness. Frovatriptan is useful for patients with prolonged migraine attacks and high headache recurrence rate. It is also beneficial in patients who have menstrually associated migraine. Frovatriptan displays the longest half-life of all the triptans (26hours), has a relatively short time to Tmax (2-3hours), and has few drug interactions. In a direct comparative study, frovatriptan was better tolerated than sumatriptan, with a lower rate of adverse events (36% versus 43%). The most common adverse effects of frovatriptan are dizziness, nausea, fatigue, somnolence, paresthesias and flushing.At present, zolmitriptan is available in an oral formulation. However, a nasal spray formulation has been recently developed. The main advantage of the zolmitriptan nasal spray is its rapid onset of action, with research showing that zolmitriptan plasma levels can be detected in heathy volunteers as early as 5min after nasal administration. It has been shown to be effective and tolerable in acute migraine treatment, with the most common adverse event being unusual taste. Compared with nasal sumatriptan, zolmitriptan nasal spray has a similar time to onset of action, a higher 2hour headache reponse (70% vs. 64%), but lower 2hour pain-free response (36% vs. 42%), and a lower recurrence rate (25% vs. 30-45%). Zolmitriptan nasal spray should be considered when patients have rapid-onset attacks, especially when associated with nausea or vomiting. The last of the new emerging treatments for acute migraine to be considered in this article is the butyrophenone neuroleptic droperidol. This drug has been used extensively for anesthesia induction and as an antiemetic. Recent research has shown that it is also an effective drug for treatment of acute migraine headache and the associated symptoms of nausea and vomiting. The relatively high rate of CNS adverse events (akathisia, somnolence and anxiety), along with the rare but reported association with prolonged QT interval and resultant Torsades de Pointes, indicate droperidol should not be used as a first-line treatment for acute migraine. This drug should be reserved as a rescue medication in an emergency room setting for patients with severe attacks, when the patient cannot tolerate or is unable to take triptans.