What is the best prophylactic treatment for cluster headaches?

Best Prophylactic Treatment for Cluster Headaches

Galcanezumab 300 mg subcutaneously once monthly is the first-line prophylactic treatment for episodic cluster headache, as it has the strongest evidence among available prophylactic options according to the 2023 VA/DoD guidelines. 1, 2

Treatment Algorithm by Cluster Headache Type

For Episodic Cluster Headache (with remission periods)

• Galcanezumab 300 mg subcutaneously once monthly is the recommended first-line prophylactic agent 1, 2
• This represents a weak recommendation FOR use, but it is the strongest evidence available among all prophylactic options 1, 2
• In the pivotal trial, galcanezumab reduced weekly attack frequency by 3.5 attacks more than placebo (8.7 vs 5.2 attacks reduction) across weeks 1-3 3, 4
• 71% of patients achieved ≥50% reduction in attack frequency at week 3, compared to 53% with placebo 3, 4
• Monitor for injection site reactions and hypersensitivity 1

For Chronic Cluster Headache (attacks >1 year without remission)

• Do NOT use galcanezumab for chronic cluster headache - the VA/DoD guidelines provide a weak recommendation AGAINST its use in this population 1, 2
• Verapamil remains an option, though the 2023 VA/DoD guidelines note insufficient evidence to recommend for or against it for chronic cluster headache 1, 2
• If using verapamil, start at least 240 mg daily with dose titration based on efficacy and tolerability 2, 5

Verapamil Considerations (When Used)

• Obtain baseline ECG before initiating therapy 2
• Monitor PR interval with ECG when using doses >360 mg daily, as cluster headache often requires doses double those used in cardiology 2
• Contraindicated in patients with impaired ventricular function, heart failure, or wide-complex tachycardias 2
• Verapamil is commonly used in clinical practice, though recent guidelines note insufficient evidence to formally recommend for or against it 1, 2, 5

Bridging Therapy While Establishing Prophylaxis

• Use acute treatments during the prophylaxis initiation period 1, 2
• Subcutaneous sumatriptan 6 mg is first-line for acute attacks (70-82% efficacy within 15 minutes) 1, 2, 6
• 100% oxygen at 12 L/min for 15 minutes is equally effective and has no cardiovascular contraindications 1, 2, 6
• Intranasal zolmitriptan 10 mg is an alternative triptan option 1, 2, 6
• Oral corticosteroids (prednisolone) can serve as transitional prophylaxis until maintenance therapy becomes effective 5

Critical Pitfalls to Avoid

• Do not confuse episodic and chronic cluster headache - galcanezumab is only appropriate for episodic cluster headache and should be discontinued if the patient progresses to chronic cluster headache 1, 2
• Do not confuse acute and prophylactic treatments - oxygen and triptans treat individual attacks, not prevention 1, 6
• Do not use triptans in patients with ischemic heart disease, vasospastic coronary disease, or uncontrolled hypertension 6
• Do not combine triptans with ergotamine derivatives due to additive vasoconstrictive effects 6
• When using verapamil at high doses (>360 mg daily), failure to obtain ECG monitoring can miss dangerous PR interval prolongation 2

Emerging Evidence

• Some case series suggest galcanezumab may be effective in refractory chronic cluster headache (83% achieved >50% frequency reduction), though this contradicts guideline recommendations and requires further randomized controlled trial evidence 7
• Other agents with possible efficacy include lithium, topiramate, divalproex sodium, and melatonin, though evidence is limited 5, 8