From the Guidelines
Recent studies suggest that galcanezumab is a promising treatment for preventing episodic cluster headaches, as evidenced by the 2024 clinical practice guideline for the management of headache 1.
Emerging Treatments
Emerging treatments for cluster headaches include:
- Non-invasive vagus nerve stimulation devices like gammaCore, which can abort attacks when used at onset
- CGRP monoclonal antibodies such as galcanezumab (Emgality) at 120mg monthly injections, which have shown effectiveness for both prevention and acute treatment 1
- Psilocybin and LSD microdosing, which are being investigated for their potential to interrupt cluster cycles, though these remain experimental
- Neuromodulation techniques including sphenopalatine ganglion stimulation and deep brain stimulation of the hypothalamus, which show promise for treatment-resistant cases
Current Recommendations
Current recommendations for the treatment of cluster headaches include:
- Subcutaneous sumatriptan (6 mg) or intranasal zolmitriptan (10 mg) for the short-term treatment of cluster headache 1
- Normobaric oxygen therapy for the short-term treatment of cluster headache 1
- Noninvasive vagus nerve stimulation for the short-term treatment of episodic cluster headache 1
Ongoing Research
Ongoing research is focused on understanding the genetic components of cluster headaches, with several gene variants identified that may contribute to susceptibility. Improved neuroimaging techniques are helping to visualize hypothalamic activity during attacks, enhancing our understanding of the condition's pathophysiology. These developments reflect our growing understanding that cluster headaches involve complex neurological pathways including the hypothalamus, trigeminal nerve, and autonomic nervous system, offering multiple targets for intervention and potentially more personalized treatment approaches in the future.
Key Considerations
When considering treatment options for cluster headaches, it is essential to prioritize morbidity, mortality, and quality of life. The most recent and highest-quality study available should guide treatment decisions, and in this case, galcanezumab is a promising option for preventing episodic cluster headaches 1.
From the FDA Drug Label
The efficacy of EMGALITY was evaluated for the treatment of episodic cluster headache in a randomized, 8-week, double-blind, placebo-controlled study (Study 4) EMGALITY 300 mg demonstrated statistically significant improvements for efficacy endpoints compared to placebo, as summarized in Table 4. Table 4: Efficacy Endpoints in Study 4 EMGALITY 300 mg N = 49Placebo N = 57 Mean Reduction in Weekly Cluster Headache Attack Frequency (over Weeks 1 to 3) Prospective Baseline Cluster Headache Attack Frequency 17.8 17. 3 Mean change from baseline -8.7 -5.2 Difference from placebo -3.5 p-value 0.036 ≥50% Weekly Cluster Headache Attack Frequency Responders (at Week 3) % Responders 71.4% 52.6% Difference from placebo 18.8% p-value 0. 046
The research around cluster headaches is emerging with galcanezumab (EMGALITY) showing statistically significant improvements in reducing weekly cluster headache attack frequency.
- The study found a mean reduction of 8.7 weekly cluster headache attacks with EMGALITY 300 mg compared to 5.2 with placebo.
- 71.4% of patients treated with EMGALITY 300 mg achieved a 50% or greater reduction in weekly cluster headache attack frequency at Week 3, compared to 52.6% with placebo 2.
From the Research
New and Emerging Research on Cluster Headaches
- Cluster headaches are a debilitating primary headache disorder affecting approximately 0.1% of the population worldwide 3.
- Recent studies have identified crucial neuropeptides and brain structures as emerging treatment targets, including calcitonin gene-related peptide antibodies, non-invasive vagus nerve stimulation, sphenopalatine ganglion stimulation, and somatostatin receptor agonists 3.
- Emerging treatment options are being investigated, such as ketamine, onabotulinumtoxinA, lysergic acid, and sodium oxybate 4.
- Monoclonal antibodies to the calcitonin gene-related peptide have shown efficacy for episodic cluster headache 4.
Current Treatment Options
- Acute treatments include triptans, high-flow oxygen, and interim treatment options such as corticosteroids and greater occipital nerve block 3, 5, 6, 7.
- Preventive treatments include verapamil, lithium, melatonin, and topiramate, with verapamil being the most effective 3, 6, 7, 4.
- Transitional prophylaxis using corticosteroids can help control attacks at the beginning of a cluster period 7.
Advances in Treatment
- Non-invasive vagus nerve stimulation and sphenopalatine ganglion stimulation are emerging as potential treatment options 3.
- Hypothalamic deep brain stimulation is a promising surgical procedure for chronic refractory cluster headache 6.
- Peripheral neural blockade is effective for short-term pain control 7.