Intranasal ketamine for acute cluster headache attacks-Results from a proof-of-concept open-label trial
In an open‑label pilot in chronic cluster headache, intranasal ketamine did not meet the predefined 50% pain reduction at 15 minutes but produced a significant mean 59% reduction at 30 minutes (69% of evaluable patients ≤4/10) with no serious adverse events. These results indicate intranasal ketamine may be an effective acute treatment at 30 minutes and warrant larger controlled trials, with caution regarding ketamine’s abuse potential.
Authors
- Petersen, A. S.
- Pedersen, A. S.
- Pedersen, O.
Published
Abstract
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 < 0.001, N = 16) and 11 out of 16 (69%) scored 4 or below on the NRS. Four patients received rescue medication 15 min after the first ketamine application and were therefore excluded from the analysis at 30 min. Half of the patients preferred ketamine to oxygen and/or sumatriptan injection. No serious adverse events were identified during the trial.
Conclusion
Intranasal ketamine may be an effective acute treatment for CH at 30 min but should be tested in a larger controlled design. Patients and physicians should be conscious of the abuse potential of ketamine.
Research Summary of 'Intranasal ketamine for acute cluster headache attacks-Results from a proof-of-concept open-label trial'
Introduction
Cluster headache (CH) attacks are typically treated acutely with triptans (subcutaneous or intranasal) and high-flow oxygen, but an estimated 20%–30% of patients gain insufficient relief from these first-line options. Previous trials concentrated mainly on episodic CH, and patients with chronic cluster headache (cCH) often respond less well to triptans and oxygen. A few alternative acute modalities exist (for example intranasal lidocaine, octreotide, or neurostimulation) but each has practical or safety limitations and some are unavailable, leaving a treatment gap for severely affected, refractory patients. Petersen and colleagues conducted a proof-of-concept, open-label pilot study to evaluate whether intranasal racemic ketamine could be an effective and safe acute treatment for single CH attacks in people with cCH. The stated aim was to assess effect and tolerability under supervised, in-hospital conditions with an emphasis on short-term pain reduction after administration.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Petersen, A. S., Pedersen, A. S., Barloese, M. C. J., Holm, P., Pedersen, O., Jensen, R. H., & Snoer, A. H. (2022). Intranasal ketamine for acute cluster headache attacks-Results from a proof-of-concept open-label trial. Headache: The Journal of Head and Face Pain, 62(1), 26-35. https://doi.org/10.1111/head.14220
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