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Ask the Expert: Intranasal Ketamine for Migraine Therapy

QUESTION: Is intranasal ketamine an effective treatment option for migraine with aura when all other therapies have failed?

ANSWER: Migraines can be a debilitating condition, greatly reducing a patient’s quality of life. The characteristics of a migraine, including the frequency, duration, and degree of disability, may differ significantly among patients as well as among attacks in a single patient. Migraine prevention is preferred; however, acute treatment may still be necessary for some patients when prevention fails.1

Acute migraine treatment options include: serotonin receptor agonists (triptans), ergot alkaloids and derivatives, antiemetics, non-opiate analgesics, opiate analgesics, and corticosteroids. Little evidence is available supporting additional therapies for the treatment of acute migraine when these treatment options fail.1

One possible treatment option is ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist. NMDA is a type of glutamate receptor. It has been hypothesized that glutamate-positive neurons are responsible for exciting the pain-relay in migraines. Ketamine, as a glutamate receptor antagonist, is therefore hypothesized to interfere with this process.2

Clinical Evidence

Only one study has looked at ketamine in the treatment of acute migraine.3 Kaube et al evaluated the use of intranasal ketamine in the treatment of 11 patients with familial hemiplegic migraine (FHM). Patients suffering from FHM are known to have auras that last for hours to days. Since ketamine has a history of dependence along with other adverse effects, patients with a history of addiction or other psychiatric disease, uncontrolled hypertension, hyperthyroidism, and glaucoma were excluded from the study. The 11 patients were given a supervised dose of 25 mg of intranasal ketamine to determine if they were able to tolerate the medication. They were then discharged with instructions to administer their next dose at the onset of a migraine attack and record treatment effects on a questionnaire every 15 minutes following administration. A total of 25 migraine attacks were treated with ketamine and recorded. Five of the 11 patients reported an improvement of all of their symptoms, including limb movement, visual disturbances, dysphasia, and duration of symptoms in a total of 14 attacks. It is not clear as to why 5 patients responded so favorably to the treatment, while the other 6 received no clinical benefit.

In summary, a single study has investigated the use of ketamine for acute migraine treatment in patients with FHM. This study found benefit in fewer than half of the patients receiving treatment. Characteristics resulting in patient response versus nonresponse are unclear. Further study is recommended before recommending the use of ketamine as a routine treatment option in the management of acute migraine.

Last updated on: November 4, 2013
First published on: September 1, 2013