Assessing Cognitive Function over Time in Patients with Refractory Chronic Migraine Who Received Ketamine Infusions:...

Ketamine infusions are used in the inpatient setting for refractory chronic migraine but are associated with neurotoxicity in rodents at high doses and memory deficits in illicit users. The relationship between ketamine infusions and cognitive function in refractory chronic migraine patients after infusions is unknown. We aimed to determine if patients receiving ketamine infusions for refractory chronic migraine experience changes in cognitive function as assessed by the telephone Montreal Cognitive Assessment.

Adults 18 years or older who were diagnosed with refractory chronic migraine and met criteria for hospitalization with an elective ketamine infusion were recruited for this prospective observational study. All patients had Migraine Disability Assessment grade IV (severe disability) and had previously failed an inpatient treatment with at least one other intravenous infusion. Baseline assessments included current and average pain levels, monthly migraine days, depression history, medications, and initial assessments of the telephone Montreal Cognitive Assessment, Migraine Disability Assessment, and Headache Impact Test-6. Patients were admitted to a dedicated headache unit within 1 month of baseline assessments to undergo a 5-day continuous ketamine infusion to a maximum rate of 1 mg/kg/h. The aforementioned assessments were then repeated at 1, 6, and 12 months. The primary outcome was the change over time in the telephone Montreal Cognitive Assessment, which was analyzed using generalized estimating equations adjusted for age and sex.

A total of 23 patients were analyzed. The mean age was 44.8 $\pm$ 11.5 years, and 87% were female. A history of depression was present in 82.6%. The estimated marginal mean telephone Montreal Cognitive Assessment score changed from 18.8 $\pm$ 0.7 to 19.9 $\pm$ 0.7 at 1 month (p < 0.001), 19.2 $\pm$ 0.8 at 6 months (p = 0.390), and 18.3 $\pm$ 0.9 at 12 months (p = 0.382). Only the change at 1 month reached the minimal clinically important difference of 1 point. Monthly migraine days decreased from a baseline of 27.1 $\pm$ 1.6 to 24.4 $\pm$ 2.1 at 1 month (p = 0.08), 22.4 $\pm$ 2.3 at 6 months (p = 0.05), and 22.3 $\pm$ 2.2 at 12 months (p = 0.026).

The study suggests that measurable cognitive impairment did not occur over the course of the 1-year study period in most patients with refractory chronic migraine after receiving a ketamine infusion. However, a few patients experienced worsening telephone Montreal Cognitive Assessment scores, and furthermore, the small sample size and lack of a control group prevent any definitive conclusions. Larger follow-up studies would further establish the safety of ketamine treatment in headache or pain.