Anesthesia in the News
  • New Data on Intranasal Ketamine for Chronic Refractive Migraine

    Intranasal (IN) ketamine is emerging as a clinical option to tackle pain stemming from chronic refractory migraine in patients who have failed to respond to at least 5 classes of preventive treatment.  In a recent study, most patients reported greater effectiveness and improved quality of life with IN ketamine use.

    In the study, presented at the most recent meeting of the American Society of Regional Anesthesia and Pain Medicine, nearly half (49%) of subjects using IN ketamine to treat chronic refractory migraine reported in interviews that the treatment was “very effective.”  An additional 40% reported that the treatment was “somewhat effective.”  However, nearly three-fourths (74%) of all study subjects reported at least 1 adverse event during treatment.  Yet despite the occurrence of adverse events, many patients elected to continue IN ketamine treatment.

    Migraine patients stayed with the treatment

    The retrospective study, conducted at the Jefferson Headache Center at Jefferson Medical Center in Philadelphia, looked at 169 patients identified through an electronic medical record query who suffered from chronic refractory migraine and had been prescribed IN ketamine (10 mg).  The cohort was 80% female and ranged in age from 30 to 58 years.  The researchers conducted interviews with the subjects to collect data regarding demographics, diagnosis, medication history, ketamine usage, treatment response, and adverse events.  The 3 most common adverse effects reported were fatigue, visual disturbance, and the most common, “altered mental status.”

    Prior treatments fell short

    Overall, the patient cohort reported 25 (±9) headache days per month.  Most (59%) patients began use of IN ketamine due to incomplete responses to prior treatments for migraine that are approved by the American Headache Society, including onabotulinumtoxinA injection, calcitonin gene-related peptide receptor agonists, and monoclonal antibodies.

    As a group, the average study patient reported using “roughly” 8 sprays per day, 12 days per month.  At the time of the interviews, 65% of the respondents were still using IN ketamine.  Patients who had previously tried more alternate treatments (odds ratio [OR], 1.1; 95% CI, 1.03-1.27) and those who were currently using ketamine (OR, 4.7; 95% CI, 2.36-9.57) were more likely to report that IN ketamine was effective.

    In an interview, Hsiangkuo Scott Yuan, MD, PhD, an associate professor of neurology and headache specialist at Jefferson Medical Center who presented the data, hypothesized about the patients’ rationale for persisting with the treatment.  “The continuation rate is quite high, despite having some adverse effects.  It could mean at least two things.  These refractory patients don’t have any other drug to use, so even though ketamine has adverse effects, they still have to use it as long as it works.  Or ketamine’s adverse effects are more tolerated.”

    How its migraine use came about

    Ketamine began being used as an anesthetic during the 1960s following its approval by the FDA and has been administered in both human and veterinary medicine ever since.  It was commonly used on the battlefield in Vietnam and continues to be a regular agent in surgical anesthesia administration.

    When administered in lower doses than for anesthesia, providers and researchers have found that ketamine can relieve pain caused by several conditions.  Use of the drug for migraine sufferers presenting in the emergency room came about during a shortage of dihydroergotamine, a frequently used medication for persistent migraine attacks which failed to respond to other therapies.

    The outpatient study source

    IN ketamine is already in use in inpatient settings to treat chronic refractory migraine.  However, its serious side effects such as hallucinations, “out of body” experiences, and vivid dreams as well as concerns over its substance abuse potential have limited the drug’s use as a pain medication.  The FDA’s approval of IN ketamine for treatment of refractory depression gave the researchers a population in which they could conduct the retrospective study of the drug’s effectiveness and safety in treating patients who suffer from chronic refractory migraine outside of the inpatient setting.

    Provisos and future plans

    Yuan notes that, due to the single-center retrospective nature of the study, problems with selection and recall bias could have affected the results, and that larger double-blind, placebo-controlled studies are needed to confirm the findings.  In fact, Yuan reports that he hopes to initiate a prospective observational study with predefined outcomes captured longitudinally (via headache diary) in order to better understand the effectiveness of intranasal ketamine in the real-world setting.

    Listen to Dr. Yaun’s presentation and view Poster 2581 “Real-World Study of Intranasal Ketamine for use in Refractory Migraine” at


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