To study the efficacy of intranasal (IN) ketamine as treatment for refractory headache. 

Ketamine infusion has been used for treatment of refractory headache. IN ketamine offers an alternative option beyond the inpatient setting for acute treatment. However, its clinical efficacy and safety in this patient population has not been reported.

We received International Review Board approval for our retrospective phone interview survey designed to assess the efficacy and adverse effects of IN ketamine, which was formulated at a local compounding pharmacy. Two hundred forty-five refractory headache patients prescribed IN ketamine from January 2019 through February 2020 were identified in our electronic medical records. 

We interviewed 168 subjects (134 female) with a mean age of 44.5±13.8 years old. One hundred forty-one (83.9%) had a primary headache diagnosis of chronic migraine, and 107 (63.7%) were current IN ketamine users. The mean usage was 11.8±8.9 days per month and 7.9±6.9 sprays per day. The mean headache intensity (0-10 numerical pain scale) pre- and post-IN ketamine was 7.6±1.7 and 4.7±2.2, respectively (p<0.01 by paired t-test). The mean time to experience headache relief was 74.1±262.9 minutes. IN ketamine offered relief 70.8% of the time. One hundred twenty (71.4%) subjects affirmed using less additional acute medication to treat pain attacks while using IN ketamine. Adverse events included diplopia or blurred vision (20.8%), fatigue (20.8%), nausea (15.5%), vivid dreams (10.1%), hallucinations (7.7%), vomiting (3%), tremor (2.4%), extreme fear (1.8%), and myoclonus (1.2%). Forty-four (26.2%) subjects denied any adverse effects. 

Based on our single-center retrospective study, IN ketamine can be a potential acute treatment for patients with refractory headache to reduce headache intensity with a few adverse effects.