What are the treatment options for a patient presenting with cluster headaches?

Cluster Headache Treatment

For acute cluster headache attacks, use subcutaneous sumatriptan 6 mg or 100% oxygen at ≥12 L/min for 15 minutes as first-line therapy; for episodic cluster headache prevention, galcanezumab has the strongest evidence, while verapamil (≥240 mg daily) remains a commonly used alternative despite insufficient formal evidence. 1, 2, 3

Acute Treatment Algorithm

First-Line Acute Options (choose based on availability and patient factors):

• Subcutaneous sumatriptan 6 mg provides relief in 70% of patients within 1 hour and 49% are pain-free within 1 hour 4, 3

  • Onset of relief occurs in less than 10 minutes 4
  • For cluster headache specifically, 49% achieve relief at 10 minutes and 75% at 15 minutes 4

• 100% oxygen at flow rate of at least 12 L/min for 15 minutes (normobaric oxygen therapy) 1, 2, 3

  • Must use non-rebreather mask with adequate flow rate (≥12 L/min is critical) 1, 5

Alternative Acute Options:

• Intranasal zolmitriptan 10 mg if subcutaneous route is not feasible 1, 2

• Non-invasive vagus nerve stimulation for episodic cluster headache (short-term treatment) 1

Preventive Treatment Algorithm

For Episodic Cluster Headache:

First-line: Galcanezumab has the strongest evidence among prophylactic options per 2023 VA/DoD guidelines 1, 2

• This represents a weak recommendation FOR galcanezumab specifically for episodic (not chronic) cluster headache 1, 2
• Monitor for injection site reactions and hypersensitivity 2

Alternative: Verapamil at daily dose of at least 240 mg (maximum dose depends on efficacy and tolerability) 1, 3

• Note: VA/DoD guidelines state insufficient evidence to recommend for or against verapamil, though it remains commonly used 1, 5
• Critical cardiac monitoring required: Obtain baseline ECG before initiating therapy 1, 5
• Monitor PR interval with ECG when using doses >360 mg daily (doses in cluster headache may be double those used in cardiology) 1
• Contraindications: Impaired ventricular function, heart failure, wide-complex tachycardias, AV block greater than first degree, SA node dysfunction without pacemaker, decompensated systolic heart failure, severe LV dysfunction, hypotension 1
• Drug interactions: Verapamil is a moderate CYP3A4 and P-glycoprotein inhibitor; contraindicated with dofetilide; requires careful monitoring with dabigatran, edoxaban, rivaroxaban, flecainide, simvastatin, digoxin; avoid grapefruit juice 1

Other alternatives: Lithium, topiramate 3

For Chronic Cluster Headache:

Do NOT use galcanezumab (weak recommendation against for chronic cluster headache) 1, 2

Consider verapamil despite insufficient evidence, as it remains commonly used 1

• Same cardiac monitoring and contraindications apply as above 1, 5

Bridge Therapy (transitional prophylaxis while waiting for preventive to take effect):

• Corticosteroids: At least 100 mg prednisone (or equivalent) orally OR up to 500 mg IV per day over 5 days 3

• Greater occipital nerve block 3

Diagnostic Criteria to Confirm Before Treatment

Cluster headache requires five attacks with frequency of 1-8 attacks per day, featuring: 6

• Severe unilateral orbital, supraorbital, or temporal pain lasting 15-180 minutes (untreated) 6

• At least one ipsilateral autonomic feature: lacrimation, nasal congestion, rhinorrhea, forehead/facial sweating, ptosis, miosis, or eyelid edema 6

Critical Pitfalls to Avoid

• Do not confuse episodic vs. chronic cluster headache when selecting galcanezumab—it is only appropriate for episodic cluster headache 1, 2

• Do not use inadequate oxygen flow rates—must be ≥12 L/min, not the typical 2-6 L/min used for other conditions 1, 5, 3

• Do not skip cardiac monitoring with verapamil—baseline ECG is mandatory, and ongoing monitoring is required at higher doses due to substantially higher doses used in cluster headache compared to cardiovascular indications 1, 5

• Do not use implantable sphenopalatine ganglion stimulator (weak recommendation against) 1

• Do not confuse acute vs. preventive treatments—oxygen and sumatriptan are for individual attacks, not prevention 2

Treatment Selection Based on Clinical Scenario

Episodic cluster headache with frequent attacks:

• Acute: Subcutaneous sumatriptan 6 mg + home oxygen setup 1, 4, 3
• Preventive: Galcanezumab first-line 1, 2
• Bridge: Prednisone ≥100 mg daily while establishing prophylaxis 3

Chronic cluster headache (attacks >1 year without remission):

• Acute: Same as episodic 1, 4, 3
• Preventive: Verapamil with cardiac monitoring (galcanezumab not recommended) 1

Contraindication to triptans or verapamil:

• Acute: 100% oxygen at ≥12 L/min 1, 3
• Preventive: Consider lithium or topiramate 3