AAN 2024 | IV ketamine for treating pediatric headache

It’s an NMDA receptor antagonist that’s previously shown benefit in chronic pain syndromes that are not headache specific, as well as refractory mood disorders. It’s showing a lot of promise as an additional treatment option for patients who have failed traditional therapies. So, most routes are usually IV migraine cocktails, valproic acid and DHE. Many patients either just don’t respond to those medications or have contraindications so don’t tolerate them and are left with ongoing pain. Ketamine is another route, another different mechanism to treat those patients.

Our institution has a continuous ketamine protocol; patients are admitted for up to three days of IV ketamine, depending on how they tolerate and their benefit. Being in our hospitals, I see a lot of these patients, and I realized there wasn’t a lot of literature on the actual efficacy, and no real guidance on who would be a good responder to it. That brought the investigation into it. We found that there was a pretty reasonable pain response to it. At discharge, there was about a median percent pain reduction of about 40%, so 40% less than their initial pain, and about 45% of patients who discharged had at least a 50% reduction in their initial pain, which is usually considered a clinically significant reduction. So, a pretty good response. We looked at the tolerability of it and there were no serious adverse events at all: there was no escalation of care, in terms of side effects it was very well tolerated. Only 7% of the encounters had to discontinue the ketamine due to side effects. The vast majority tolerated really well. The most common side effects were nausea, dizziness, and hallucinations, and often those are easily treated with a little bit lorazepam, as needed.

I’m a pediatric neurologist, so it is pediatric patients. Our group for the study was 5 to 21 years of age inclusive, but it ended up having a median age of 16 years. We had 68 encounters comprised of 41 unique patients. 85% were female, and most of them had a diagnosis of chronic migraine without aura. They usually had about ten days of headache exacerbation at the time of presentation, or ten days of status migrainosus.

We didn’t divide it up by age when we looked at it. It’s an interesting question. But, we did look at if there was an association of age overall and there was no relationship between age and the pain reduction. So it doesn’t seem like there’s a clear response, but there are other ways to cut that data.

We would love to have randomized data that proves our efficacy in a controlled fashion. It’s really hard to do in pediatrics because many things are already off-label, and then it’s often hard to get funding for a lot of those projects as well. Those two initial hurdles make it difficult. We were talking about at least trying to have more of a prospective data analysis, more looking at the recurrence of it, in terms of the lasting benefit of the ketamine. In our study, for patients who recurred, they recurred about a week after they got discharged from ketamine. Only 36% of patients had recurrence within a month. So a little over 60% didn’t recur in a month, which is pretty good. We defined recurrence as coming back to a clinic visit or a phone call saying, “my headache’s back” and the provider did a therapy change, or presenting to the ER, infusion center, or admission for recurrent headache that required treatment. We were talking about potentially trying to figure out if that lasted longer than we even thought by looking at the actual patient responses instead of just the points of care contact.