DENVER — , new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.
Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
Statistically Significant Pain Relief
“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said.
“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted.
Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine.
They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases.
On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis.
The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter.
Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.
Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said.
There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
‘Exciting Starting Point’
At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001).
“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said.
He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge.
In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours.
The researchers also tried to tease out which patients might respond best to ketamine.
“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted.
“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said.
She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.”