Objectives: To compare the effectiveness and safety of parenteral pharmacological interventions to treat migraine headaches in adults presenting to the emergency department (ED).
Data sources: In consultation with a librarian, we searched 10 electronic databases, conference proceedings, clinical trials registers, and reference lists.
Methods: Two reviewers independently selected studies, assessed risk of bias, extracted data, and graded the strength of evidence (SOE). Data were pooled using a random-effects model. A mixed-treatment analysis was performed for pain relief and akathisia.
Results: Nine classes of drugs were investigated in 71 controlled trials. Risk of bias was low for 28 percent of the trials, unclear for 61 percent, and high for 11 percent. Overall, active interventions were more effective than placebo for pain relief and headache recurrence. Most head-to-head comparisons for pain reduction were based on single trials resulting in insufficient SOE. The mixed-treatment analysis showed that the most effective treatments were combination therapy (i.e., dihydroergotamine [DHE] added to either neuroleptics or metoclopramide) or neuroleptic monotherapy (low SOE), with a pain reduction of approximately 40 mm on a visual analog scale (VAS). Metoclopramide monotherapy, opioids, and nonsteroidal anti-inflammatories (NSAIDs) were the next most effective treatments, with a pain reduction of approximately 24 mm (low SOE). Other agents (e.g., DHE, triptans, orphan agents) were less effective, with a pain reduction of approximately 12–16 mm.
Short-term side effects were infrequent, and considered minor and self-limiting. No two studies reported the same side effects for the same pair of interventions; therefore, the SOE is insufficient to conclude which treatment results in more or fewer adverse effects. Based on the mixed-treatment analysis, the odds of experiencing akathisia symptoms following administration of metoclopramide or neuroleptic agents were 9.4 and 10.7 times greater than with placebo, respectively. The risk of sedation following administration of metoclopramide or neuroleptic agents was 17 percent. The most common short-term side effects for triptans were skin reactions, local reactions, and sedation. For patients receiving DHE, the most common side effects were skin and local reactions, sedation, digestive issues, nausea or vomiting, and chest symptoms. Few side effects were reported for NSAIDS or opioids. In patients receiving magnesium sulfate, high rates of skin flushing and local reactions were reported.
The available evidence failed to identify variable responsiveness based on subgroups. Migraine relapse can be prevented with intravenous systemic corticosteroids provided in the ED, particularly in patients with prolonged headaches (>72 hours).
Conclusion: Many agents are effective in the treatment of acute migraine headache when compared with placebo. Several treatments provide insufficient evidence for continued use. Neuroleptic monotherapy and DHE in combination with either metoclopramide or neuroleptics appear to be the most effective options for pain relief (VAS). Systemic corticosteroids effectively prevent headache relapse, especially in patients with prolonged headaches. More research is required to identify the most effective parenteral treatments for adults with acute migraine.