Intranasal ketamine for acute cluster headache attacks—Results from a proof‐of‐concept open‐label trial

Objective To investigate the safety and efficacy of intranasal ketamine for the treatment of a single cluster headache (CH) attack. Background Acute treatment options for patients with CH who have an insufficient response to oxygen and triptans are limited. Intranasal ketamine has anecdotally been successful in treating a CH attack. Methods We conducted an open‐label pilot study enrolling 23 patients with chronic CH (International Classification of Headache Disorders, 3rd edition), and of these, 20 patients treated a single CH attack with intranasal ketamine. Under in‐hospital observation, patients received 15 mg of intranasal ketamine every 6 min a maximum of five times. The primary endpoint was a 50% reduction in pain intensity within 15 min after initiating treatment. Results The primary endpoint was not met; 15 min after the first ketamine administration, the mean reduction in pain intensity was 1.1 (95% confidence interval [CI]: −0.6 to 2.7, p = 0.188) on the numeric rating scale (NRS), equivalent to a 15% reduction in pain intensity. However, 30 min after the first application, the pain intensity was reduced by 59% on an 11‐point NRS (mean difference: 4.3, 95% CI: 2.4–6.2, p