What is the best treatment approach for a patient with cluster headaches?

Cluster Headache Treatment

Acute Treatment: First-Line Options

For acute cluster headache attacks, use subcutaneous sumatriptan 6 mg OR 100% oxygen at ≥12 L/min for 15 minutes as first-line therapy. 1, 2, 3

Subcutaneous Sumatriptan

• Delivers relief in 70% of patients within 1 hour and 82% within 2 hours 3
• Onset of relief occurs in less than 10 minutes 3
• For cluster headache specifically, 49% achieve relief at 10 minutes and 74-75% at 15 minutes 3
• Dose: 6 mg subcutaneous (the 12 mg dose showed no additional benefit) 3

High-Flow Oxygen

• Administer 100% oxygen (normobaric) at flow rates of at least 12 L/min for 15 minutes 1, 2, 4
• This is a strong recommendation from multiple guideline societies including the American Academy of Neurology 4, 5

Alternative Acute Options

• Intranasal zolmitriptan 10 mg is an alternative if subcutaneous sumatriptan is contraindicated 1, 2
• Noninvasive vagus nerve stimulation is suggested for episodic cluster headache 2, 5

---

Prophylactic Treatment: Episodic vs Chronic Cluster Headache

For Episodic Cluster Headache

Galcanezumab is the first-line prophylactic treatment for episodic cluster headache, representing the strongest evidence among available options. 1, 2

• The 2023 VA/DoD guidelines provide a weak recommendation FOR galcanezumab specifically for episodic cluster headache 1, 2
• Monitor for injection site reactions and hypersensitivity 1
• Critical pitfall: Do NOT use galcanezumab for chronic cluster headache (weak recommendation AGAINST) 1, 2

For Chronic Cluster Headache

Verapamil remains the mainstay for chronic cluster headache prophylaxis, despite insufficient evidence in recent guidelines. 2, 4

• Start at 240 mg daily minimum; maximum dose depends on efficacy and tolerability 2, 4, 5
• Cardiac monitoring is mandatory: Obtain baseline ECG before initiating therapy and monitor PR interval with ECG when using doses >360 mg daily 2, 4
• Doses used in cluster headache are substantially higher than typical cardiovascular doses 4

Verapamil Contraindications (American Heart Association)

• Impaired ventricular function or heart failure 2, 4
• AV block greater than first degree or SA node dysfunction (without pacemaker) 2
• Decompensated systolic heart failure or severe LV dysfunction 2
• Hypotension 2
• Wide-complex tachycardias 4

Verapamil Drug Interactions

• Verapamil is a moderate CYP3A4 inhibitor and P-glycoprotein inhibitor 2
• Contraindicated with dofetilide 2
• Requires careful monitoring with dabigatran, edoxaban, rivaroxaban, flecainide, simvastatin, and digoxin 2
• Avoid grapefruit juice 2

---

Bridge Therapy

Use corticosteroids or occipital nerve blocks as bridge therapy while establishing prophylaxis. 1, 5

Corticosteroid Options

• Oral prednisone: at least 100 mg daily (or equivalent corticosteroid) 5
• IV corticosteroids: up to 500 mg per day over 5 days 5
• Suboccipital steroid injections have Level A evidence (the only prophylactic treatment with this designation) 6

Greater Occipital Nerve Block

• Recommended as bridge therapy 5
• Provides rapid onset while waiting for oral prophylaxis to become effective 5

---

Alternative Prophylactic Options

When first-line treatments fail or are contraindicated:

• Lithium is recommended as an alternative 5, 7
• Topiramate is recommended as an alternative 5, 7
• Gabapentin may be useful 8, 7
• Divalproex sodium may be useful 8, 7

---

Treatment Algorithm Summary

Step 1: Acute Attack Management

• Subcutaneous sumatriptan 6 mg OR 100% oxygen ≥12 L/min × 15 minutes 1, 3

Step 2: Determine Cluster Type

• Episodic (remission periods >1 month): Use galcanezumab 1, 2
• Chronic (attacks >1 year without remission): Use verapamil with cardiac monitoring 2, 4

Step 3: Bridge Therapy

• Corticosteroids (prednisone ≥100 mg daily) OR occipital nerve block while establishing prophylaxis 5, 6

Step 4: If First-Line Prophylaxis Fails

• Consider lithium, topiramate, or gabapentin 5, 7

---

Common Pitfalls to Avoid

• Do not confuse acute and prophylactic treatments—oxygen and sumatriptan are for attacks, not prevention 1
• Do not use galcanezumab for chronic cluster headache (it has a weak recommendation against) 1, 2
• Do not start verapamil without baseline ECG and plan for cardiac monitoring at doses >360 mg daily 2, 4
• Do not use implantable sphenopalatine ganglion stimulator (weak recommendation against) 2
• Do not overlook verapamil's extensive drug interaction profile, particularly the contraindication with dofetilide 2