Rescue Therapy for Acute Migraine, Part 1

Triptans, Dihydroergotamine, and Magnesium

Nancy E. Kelley, MD, PhD; Deborah E. Tepper, MD


Headache. 2012;52(1):114-128. 

In This Article

Conclusions: Triptans, DHE, and Magnesium


In the only study to use an oral triptan in the ED, 73.5% of migraineurs were pain-free at 2 hours using rizatriptan 10 mg orally dissolvable tablets. This was, however, not a randomized, controlled trial.

In terms of "percent pain-free at two hours," sumatriptan was similar to prochlorperazine (both ~40%) but inferior to metoclopramide plus diphenhydramine (59% vs 35%); this percent pain-free in the metoclopramide group (59%) was, however, substantially higher than that recorded in a separate study that compared percent pain-free at 2 hours for three doses of metoclopramide (10, 20, and 40 mg).[61] In terms of pain relief, diphenhydramine plus prochlorperazine surpassed sumatriptan; this was not the case, however, for trimethobenzamide plus diphenhydramine. Sumatriptan was faster than DHE in providing pain relief, but the advantage was not sustained over time, with headache recurrence at 24 hours being less in the DHE group. In addition, sumatriptan nasal spray was not as effective as ketorolac IV in relieving pain.

Of special note, sumatriptan was not at all effective (zero patients pain-free at 2 hours) when administration was delayed until after the development of central sensitization, as determined by the presence of cutaneous allodynia in the scalp and/or face of the patient.

Sumatriptan SQ 6 mg as a single agent was superior to placebo, with 70% having pain relief and about one third being pain-free before discharge from the ED and remaining pain-free for 24 hours. These percentages appear modest compared with phenothiazines (to be reviewed in a subsequent paper in this series), but with the minimal side effects resolving on their own before patients even leave the ED, sumatriptan certainly can be recommended as first-line therapy for migraine patients who have not developed cutaneous allodynia.

These emergent and urgent care results are similar to those of studies using triptans for outpatient treatment of their migraines in which up to 40% of individual headaches were not relieved by triptans and up to 25% of patients did not respond to triptans for any of their headaches.[62] Of some interest, in studies that looked at ED physician medication choices rather than efficacy of medications, patients treated with triptans tended to spend less time in the ED than those treated with other medications (112 minutes vs 265 minutes).[63]


As a single agent, DHE 1 mg IV or SQ has not been as effective as prochlorperazine IV, but DHE did appear to enhance the pain relief of prochlorperazine when administered 30 minutes after, as opposed to 60 minutes after, the initial dose of prochlorperazine. Relief with DHE was slower than with sumatriptan SQ; but ultimately, DHE provided similar pain relief prior to ED discharge and greater sustained pain relief at 24 hours.

Five additional studies compared the commonly used combination of DHE and metoclopramide with other active agents. This combination was superior in pain relief to ketorolac and to meperidine plus hydroxyzine (2 studies) but similar to butorphanol, valproate, and meperidine plus a neuroleptic (promethazine or metoclopramide). The question arises as to the relative contributions of DHE and metoclopramide to pain relief. One study suggested that any additional pain relief afforded by the metoclopramide may be minimal, given that the combination of DHE plus metoclopramide was no more effective for pain relief than DHE alone.

When IV DHE is used as a single agent, nausea is a common adverse event (33–67%). Pretreatment with an anti-emetic is recommended to anticipate IV DHE-induced nausea. Other side effects include sedation (22–30%), dysphoria (43%), flushing (29%), and chest discomfort (as high as 75% in one study), which usually resolve without intervention.


Magnesium can be effective in treating all symptoms of patients who have migraine with aura, although it appears effective in treating only associated symptoms of photophobia and phonophobia across all migraine patients. Using magnesium in conjunction with metoclopramide, however, may worsen the therapeutic outcome perhaps through magnesium causing cerebral vasodilation. Magnesium has minimal side effects, chief among them being loose stools. Magnesium also can lower blood pressure temporarily. When used in combination with DHE, magnesium can help mitigate the blood pressure increase at times associated with DHE. Magnesium is safe to use in pregnancy.

As noted in the introduction, Part 2 of this series will address the neuroleptics, antihistamines, serotonin (5HT)3 antagonists, valproate, and others (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine). Part 3 will address the opiates/opioids, NSAIDs, steroids, and postdischarge medications, including as well, a general discussion of all therapies presented in the 3 articles.


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