Ketamine may help to treat pain in patients with refractory chronic migraine, according to a case series published in the December 2016 Journal of Headache and Pain. IV ketamine treatment was associated with short-term improvement in pain severity in six of six patients with refractory chronic migraine.
“This study highlights the need for further research regarding new treatment options for patients who suffer daily consequences of refractory migraine and have failed many abortive and preventive medications,” said Clinton Lauritsen, MD, a Headache Fellow at Thomas Jefferson University Hospital in Philadelphia.
Clinton Lauritsen, MD
Ketamine is a dissociative anesthetic that acts on glutamate binding sites at the N-methyl-D-aspartate (NMDA) receptor, as well as at opioid, monoaminergic, cholinergic, nicotinic, and muscarinic receptors. IV ketamine was previously studied in several refractory pain conditions, including complex regional pain. While intranasal ketamine reduced the severity of migraine aura in a small randomized trial, the use of IV ketamine has only been reported in case series. Krusz et al showed improvement in pain scores in patients who used IV ketamine for refractory migraine; few side effects were reported.
Inpatient IV Ketamine
To further investigate the effect of IV ketamine in patients with intractable migraine, Dr. Lauritsen and colleagues conducted a retrospective chart review study. The researchers identified six patients with refractory chronic migraine admitted to Mount Sinai Beth Israel Hospital in New York from 2010 through 2014 for treatment with continuous IV ketamine.
Patients were given a starting dose of 0.1 mg/kg/h that was increased by 0.1 mg/kg/h every three to four hours as tolerated until the target pain score of 3 out of 10 was achieved and maintained for at least eight hours. Subsequently, the infusion was decreased by 0.2 mg/kg/h every three to four hours until the infusion rate reached 0 mg/kg/h.
The dose of ketamine was increased until maximum response was achieved or undesirable side effects, including psychomimetic and dysphoric effects, developed. Researchers used the Visual Analogue Score (VAS) at admission and during follow-up. VAS scores at different ketamine infusion rates were assessed from nursing and infusion records. Pain response was defined as a reduction in the initial VAS to a score of 3 or less. In addition, researchers attempted to contact patients for a telephone follow-up; however, they were only able to reach two of the six patients. During the telephone interview, researchers administered a questionnaire.
Pain Relief Achieved
Results from the data revealed a median age of 36.5 years; 83% of the patients were women. All of the patients were Caucasian, and the median age of migraine onset was 17. The median duration of the disease was 17 years. The mean number of failed acute migraine treatments was 18, and the mean number of failed preventive medications was 25. Pre-treatment pain scores ranged from 9 to 10.
In this small case series, all six patients with refractory migraine met the target pain relief end point with ketamine during a mean infusion period of 44 hours (range, 12 to 82 hours). Mean ketamine infusion rate at the time of pain relief end point was 0.34 mg/kg/h (range, 0.12 to 0.42 mg/kg/h). One patient reported a transient out-of-body hallucination when infusion rates were increased. This side effect, however, was resolved by decreasing the rate. No other significant side effects were reported.
Overall, IV ketamine relieved pain in patients with chronic migraine without substantial adverse effects. “However, future study of this benefit on short-term headache relief needs to be conducted in a placebo-controlled fashion,” said Dr. Lauritsen.
“It is biologically plausible that ketamine could be an effective treatment for intractable headache,” the researchers said. “Ketamine is an antagonist at NMDA receptors, blocking the excitatory action of glutamate, a neurotransmitter long implicated in the pathophysiology of migraine. Glutamate has been … implicated in induction of cortical spreading depression [and] activation of trigeminal nociceptive neurons [and may] play a role in central sensitization.”
—Erica Tricarico
Suggested Reading
Lauritsen C, Mazuera S, Lipton RB, Ashina S. Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series. J Headache Pain. 2016;17(1)106-110.