Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal (IN) ketamine may be an alternative option for outpatient care. We performed a retrospective study at a single tertiary headache center to assess the clinical effectiveness and tolerability of IN ketamine in patients with refractory chronic migraine (rCM). Candidates who received IN ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured phone interviews were conducted upon obtaining informed consent. Among 242 subjects screened, 169 (age 44.3 ± 13.8; female 79.9%) were interviewed. They reported 25.0 ± 8.7 monthly headache days and tried 6.9 ± 3.1 preventive medications. Overall, they used roughly 7.8 ± 7.0 sprays (ie., 78 mg) per day and 11.6 ± 8.9 days per month. Intranasal ketamine was reported as "very effective" in 49.1% and quality of life (QOL) was considered "much better" in 35.5%. However, 74.0% reported at least one adverse event (AE). In this retrospective study, IN ketamine can serve as an acute treatment for rCM by reducing headache intensity and improving QOL with relatively tolerable AEs. Most patients found IN ketamine effective and continued to use it despite these AEs. The study is limited by its single-center design and selection/recall biases. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of IN ketamine in patients with migraine.

IntroductionSubanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.MethodsA retrospective study was conducted at a single tertiary headache center to assess the clinical effectiveness and tolerability of intranasal ketamine in patients with refractory chronic migraine. Candidates who received intranasal ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured telephone interviews were conducted on obtaining informed consent.ResultsOf 242 subjects screened, 169 (79.9% women) of median (IQR) age 44 (22) years were interviewed. They reported a median (IQR) of 30 (9) monthly headache days and tried 4 (1) classes of preventive medications. Overall, they used 6 (6) sprays per day, with a median (IQR) of spray use of 10 (11) days per month. Intranasal ketamine was reported as ‘very effective’ in 49.1% and the quality of life was considered ‘much better’ in 35.5%. At the time of the interview, 65.1% remained current intranasal ketamine users and 74.0% reported at least one adverse event.ConclusionIn this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events. Given the potential for overuse, it should be reserved for those clearly in need of more effective rescue treatment with appropriate safety precautions. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of intranasal ketamine in patients with migraine.