Cluster Headache Treatment
For acute cluster headache attacks, use 100% oxygen at ≥12 L/min via non-rebreather mask for 15 minutes as first-line therapy, or subcutaneous sumatriptan 6 mg; for prevention, verapamil at ≥240 mg/day is the mainstay, with corticosteroids as bridge therapy until verapamil takes effect.
Acute Treatment of Cluster Headache Attacks
First-Line Acute Therapies
100% oxygen inhalation at a flow rate of at least 12 L/min via non-rebreather mask for 15 minutes is strongly recommended as first-line acute treatment, providing rapid relief in the majority of patients 1.
Subcutaneous sumatriptan 6 mg is strongly recommended as first-line acute therapy, with onset of action within 10–15 minutes and efficacy in approximately 75% of attacks 1, 2.
Subcutaneous sumatriptan should not be used in patients with ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, or within 24 hours of ergotamine derivatives 1, 3.
Alternative Acute Options
Intranasal sumatriptan 20 mg or intranasal zolmitriptan 5–10 mg are effective alternatives when subcutaneous administration is not feasible, though onset is slower (15–30 minutes) 1, 3.
Non-invasive vagus nerve stimulation (nVNS) is efficacious for acute treatment of episodic cluster headache but not for chronic cluster headache 1, 2.
Acute Therapies to Avoid
Oral triptans are not recommended for cluster headache due to slow onset relative to the brief attack duration (typically 15–180 minutes) 1, 2.
Opioids and butalbital-containing compounds should not be used for cluster headache due to lack of efficacy and risk of medication-overuse headache 1, 2.
Preventive (Prophylactic) Treatment
Bridge Therapy (Transitional Prophylaxis)
Bridge therapy is initiated immediately to provide rapid relief while waiting for maintenance prophylaxis to become effective (typically 2–4 weeks for verapamil).
Oral corticosteroids: prednisone 100 mg/day (or equivalent) for 5 days, then taper over 2–3 weeks, or intravenous methylprednisolone up to 500 mg/day for 5 days 1, 4, 3.
Greater occipital nerve block with local anesthetic (1–2% lidocaine or bupivacaine) is recommended as an alternative bridge therapy, particularly when corticosteroids are contraindicated 1, 2, 5.
Corticosteroids should be tapered gradually to avoid rebound attacks; abrupt discontinuation increases the risk of cluster recurrence 4, 3.
First-Line Maintenance Prophylaxis
Verapamil at a daily dose of at least 240 mg (titrated up to 480–960 mg/day based on efficacy and tolerability) is the mainstay of cluster headache prevention 1, 2, 3.
Verapamil requires baseline and follow-up electrocardiograms (ECG) to monitor for PR-interval prolongation and heart block, particularly at doses >480 mg/day 1, 3, 5.
Verapamil typically requires 2–4 weeks to reach full efficacy; bridge therapy with corticosteroids or occipital nerve block is used during this period 4, 2, 5.
Dose escalation of verapamil should occur in 80–120 mg increments every 1–2 weeks with ECG monitoring after each increase 3, 5.
Second-Line Maintenance Prophylaxis
Lithium carbonate 600–1200 mg/day (target serum level 0.6–1.2 mEq/L) is recommended as an alternative preventive, particularly for chronic cluster headache 1, 3, 5.
Lithium requires baseline and periodic monitoring of serum lithium levels, renal function, and thyroid function due to narrow therapeutic index and risk of toxicity 3, 5.
Topiramate 100–200 mg/day is recommended as an alternative preventive when verapamil is ineffective or contraindicated 1, 3, 5.
Galcanezumab 300 mg subcutaneous monthly (loading dose 300 mg, then 300 mg monthly) is recommended specifically for episodic cluster headache but has not demonstrated efficacy in chronic cluster headache 1, 2, 3.
Third-Line and Refractory Options
Occipital nerve stimulation (ONS) is reserved for medically refractory chronic cluster headache after failure of multiple preventive medications, but carries significant surgical risks and is not recommended as routine therapy due to side effect profile 1, 2, 5.
Deep brain stimulation (DBS) of the posterior hypothalamus is considered only for severe, treatment-refractory chronic cluster headache in specialized centers 2, 5.
Divalproex sodium 500–1500 mg/day may be useful when verapamil fails, but evidence is limited and it is contraindicated in women of childbearing potential due to teratogenicity 3, 5.
Melatonin 10 mg at bedtime has limited evidence but may be considered as adjunctive therapy 3.
Treatment Algorithm for Episodic Cluster Headache
Acute attack: 100% oxygen ≥12 L/min for 15 minutes or subcutaneous sumatriptan 6 mg 1, 2.
Initiate bridge therapy immediately: Prednisone 100 mg/day for 5 days, then taper over 2–3 weeks or greater occipital nerve block 1, 4.
Start verapamil 240 mg/day and titrate upward in 80–120 mg increments every 1–2 weeks (with ECG monitoring) until attacks are controlled or maximum tolerated dose is reached 1, 3, 5.
If verapamil fails or is contraindicated: Add or switch to lithium 600–1200 mg/day (with serum level monitoring) or topiramate 100–200 mg/day 1, 3, 5.
If episodic cluster headache persists despite verapamil and second-line agents: Consider galcanezumab 300 mg subcutaneous monthly 1, 2.
Treatment Algorithm for Chronic Cluster Headache
Acute attack: 100% oxygen ≥12 L/min for 15 minutes or subcutaneous sumatriptan 6 mg 1, 2.
Initiate bridge therapy: Prednisone 100 mg/day for 5 days, then taper or greater occipital nerve block 1, 4.
Start verapamil 240 mg/day and titrate upward (with ECG monitoring) to maximum tolerated dose (often 480–960 mg/day) 1, 3, 5.
If verapamil monotherapy fails: Add lithium 600–1200 mg/day (with serum level monitoring) to verapamil 1, 3, 5.
If combination verapamil + lithium fails: Add or switch to topiramate 100–200 mg/day 3, 5.
If medically refractory after trials of verapamil, lithium, and topiramate: Refer to headache specialist for consideration of occipital nerve stimulation or deep brain stimulation 1, 2, 5.
Dosing Summary Table
| Medication | Dose | Route | Indication |
|---|---|---|---|
| Oxygen | 100% at ≥12 L/min for 15 min | Inhalation (non-rebreather mask) | Acute attack (first-line) [1] |
| Sumatriptan | 6 mg | Subcutaneous | Acute attack (first-line) [1,2] |
| Sumatriptan | 20 mg | Intranasal | Acute attack (alternative) [1,3] |
| Zolmitriptan | 5–10 mg | Intranasal | Acute attack (alternative) [1,3] |
| Prednisone | 100 mg/day × 5 days, then taper over 2–3 weeks | Oral | Bridge therapy [1,4] |
| Verapamil | Start 240 mg/day, titrate to 480–960 mg/day | Oral | Maintenance prophylaxis (first-line) [1,3,5] |
| Lithium | 600–1200 mg/day (target level 0.6–1.2 mEq/L) | Oral | Maintenance prophylaxis (second-line) [1,3,5] |
| Topiramate | 100–200 mg/day | Oral | Maintenance prophylaxis (second-line) [1,3,5] |
| Galcanezumab | 300 mg loading, then 300 mg monthly | Subcutaneous | Episodic cluster headache only [1,2] |
Critical Monitoring and Safety Considerations
Verapamil: Obtain baseline ECG and repeat ECG after each dose increase above 240 mg/day; monitor for PR-interval prolongation, heart block, and hypotension 1, 3, 5.
Lithium: Monitor serum lithium levels every 3–6 months (target 0.6–1.2 mEq/L), renal function (creatinine, BUN), and thyroid function (TSH) every 6–12 months 3, 5.
Corticosteroids: Taper gradually over 2–3 weeks to avoid rebound attacks; monitor for hyperglycemia, hypertension, and mood changes during short-term use 4, 3.
Sumatriptan: Contraindicated in ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, and within 24 hours of ergotamine use 1, 3.
Common Pitfalls to Avoid
Do not use oral triptans for cluster headache; the attack duration (15–180 minutes) is too brief for oral absorption to provide meaningful relief 1, 2.
Do not delay bridge therapy while waiting for verapamil to take effect; patients will experience unnecessary suffering during the 2–4 week onset period 4, 2, 5.
Do not abruptly discontinue corticosteroids; taper over 2–3 weeks to prevent rebound cluster attacks 4, 3.
Do not prescribe galcanezumab for chronic cluster headache; it is efficacious only for episodic cluster headache 1, 2.
Do not escalate verapamil without ECG monitoring; high doses (>480 mg/day) carry significant risk of heart block 1, 3, 5.