Early treatment with NSAIDs (oral, nasal, or intramuscular ketorolac), metoclopramide, dihydroergotamine, or triptans (oral, nasal, subcutaneous) can often abort or provide significant relief of symptoms.

There is no benefit of adding intravenous diphenhydramine to intravenous metoclopramide.

 Sumatriptan may be less effective as immediate therapy for migraine attacks with aura compared to attacks without aura. In a double-blind, randomized-controlled trial of 100 patients with migraine, ginger powder appeared to be as efficacious as sumatriptan. Injectable morphine and hydromorphone are best avoided as first-line therapy.

Subanesthetic ketamine infusions may be beneficial in individuals with chronic migraine and new daily persistent headache that has not responded to other aggressive treatments. Peripheral nerve blocks may be a safe and effective way to treat headaches in older adults. Noninvasive vagus nerve stimulation has shown promise in the management of migraine and acute cluster headaches.

High-flow oxygen therapy may also provide effective treatment for all headache types in the emergency department setting. Peripheral nerve blocks for treatment-refractory migraine may be an effective therapeutic option in pregnancy. The oral 5-HT1F receptor agonist, lasmiditan, is currently in clinical trials for the treatment of acute migraine. Other causes of acute headache, such as subarachnoid hemorrhage, intracranial mass, or meningitis, require emergent treatment in the hospital.