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Cluster Headache

VERSION: 1.0 CREATED: January 29, 2026 REVISED: January 29, 2026 STATUS: Approved

DIAGNOSIS: Cluster Headache

ICD-10: G44.009 (Cluster headache syndrome, unspecified, not intractable), G44.019 (Cluster headache syndrome, unspecified, intractable), G44.001 (Episodic cluster headache, not intractable), G44.011 (Episodic cluster headache, intractable), G44.021 (Chronic cluster headache, not intractable), G44.029 (Chronic cluster headache, not intractable, unspecified), G44.031 (Chronic cluster headache, intractable), G44.039 (Chronic cluster headache, intractable, unspecified)

CPT CODES: 85025 (CBC), 80053 (CMP), 84443 (TSH), 85652 (ESR), 70544 (MRA head), 70450 (CT head), 93000 (ECG), 96365 (DHE protocol (inpatient))

SYNONYMS: Cluster headache, CH, cluster headache syndrome, histamine headache, Horton's headache, Horton's neuralgia, alarm clock headache, suicide headache, trigeminal autonomic cephalalgia, TAC, episodic cluster headache, chronic cluster headache, cluster period, cluster bout, migrainous neuralgia, ciliary neuralgia, erythroprosopalgia, Sluder's neuralgia, sphenopalatine neuralgia, Bing-Horton syndrome, autonomic cephalalgia

SCOPE: Diagnosis and management of episodic and chronic cluster headache in adults. Covers acute abortive treatment, transitional therapy, and preventive medication. Excludes other trigeminal autonomic cephalalgias (paroxysmal hemicrania, SUNCT/SUNA, hemicrania continua), migraine, and secondary causes of headache.

DEFINITIONS: - Cluster Headache: Primary headache disorder with severe unilateral orbital/supraorbital/temporal pain lasting 15-180 minutes, occurring 1-8 times daily, with ipsilateral autonomic features - Episodic Cluster Headache: Cluster periods lasting 7 days to 1 year, separated by pain-free remissions of ≥3 months - Chronic Cluster Headache: Attacks occur for >1 year without remission, or remissions lasting <3 months - Cluster Period (Bout): Period of weeks to months during which attacks occur - Trigeminal Autonomic Cephalalgias (TACs): Group of primary headaches with trigeminal pain and autonomic features (cluster, paroxysmal hemicrania, SUNCT/SUNA, hemicrania continua)

DIAGNOSTIC CRITERIA (ICHD-3):

A. At least 5 attacks fulfilling criteria B-D B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15-180 minutes (untreated) C. Either or both: 1. At least one ipsilateral autonomic symptom: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead/facial sweating, miosis, ptosis, eyelid edema 2. Sense of restlessness or agitation D. Attacks occur between 1 every other day and 8 per day E. Not better accounted for by another diagnosis

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test ED HOSP OPD ICU Rationale Target Finding
CBC (CPT 85025) - ROUTINE ROUTINE - Baseline Normal
CMP (CPT 80053) - ROUTINE ROUTINE - Baseline; before starting verapamil Normal
TSH (CPT 84443) - ROUTINE ROUTINE - Thyroid dysfunction Normal

1B. Extended Workup (Second-line)

Test ED HOSP OPD ICU Rationale Target Finding
ESR (CPT 85652) / CRP (CPT 86140) URGENT ROUTINE ROUTINE - If GCA suspected (older patient, new onset) Normal
Pituitary hormone panel - - EXT - If pituitary lesion suspected Normal

1C. Rare/Specialized

Test ED HOSP OPD ICU Rationale Target Finding
Lumbar puncture - EXT - - Only if secondary cause suspected Normal

2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study ED HOSP OPD ICU Timing Target Finding Contraindications
MRI brain with pituitary protocol - ROUTINE ROUTINE - At diagnosis (once) Rule out secondary causes (pituitary lesion, cavernous sinus lesion) Pacemaker, metal
MRA head (CPT 70544) - ROUTINE ROUTINE - If vascular lesion suspected Normal vasculature Per MRI

2B. Extended

Study ED HOSP OPD ICU Timing Target Finding Contraindications
CT head (CPT 70450) STAT STAT - - If acute concern (thunderclap, first presentation) Rule out hemorrhage None
ECG (CPT 93000) STAT STAT ROUTINE - Before verapamil; baseline Normal rhythm, PR interval None

3. TREATMENT

3A. Acute/Abortive Treatment (During Attack)

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
High-flow oxygen INH - 100% :: INH :: - :: 100% O2 at 12-15 L/min via non-rebreather mask × 15-20 min; can repeat None; safe in COPD for acute use O2 sat; usually aborts attack in 15 min STAT STAT ROUTINE -
Sumatriptan SC SC - 6 mg :: SC :: - :: 6 mg SC; may use up to 2 doses/24h (minimum 1h apart); max 12 mg/24h CAD, uncontrolled HTN, recent stroke/TIA, hemiplegic migraine Chest tightness, BP STAT STAT ROUTINE -
Sumatriptan nasal IN - 20 mg :: SC :: - :: 20 mg intranasal; less effective than SC Same as SC Same STAT STAT ROUTINE -
Zolmitriptan nasal IN - 5 mg :: IN :: - :: 5 mg intranasal; may repeat in 2h; max 10 mg/24h Same as sumatriptan Same STAT STAT ROUTINE -
Lidocaine intranasal IN - 1 mL :: - :: - :: 4% lidocaine 1 mL applied to ipsilateral nostril (head tilted back); can repeat Local anesthetic allergy May provide partial/temporary relief URGENT URGENT ROUTINE -
Octreotide SC SC - 100 mcg :: SC :: - :: 100 mcg SC; second-line if triptans contraindicated None significant GI upset - EXT EXT -

3B. Transitional (Bridge) Therapy

Purpose: Rapid suppression of attacks while preventive medication takes effect (2-3 weeks)

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Prednisone - - 60-80 mg :: - :: daily :: 60-80 mg daily × 5 days, then taper by 10 mg q3 days; OR 1 mg/kg × 5 days then rapid taper; total course ~2-3 weeks Uncontrolled DM, active infection Glucose, GI prophylaxis - STAT ROUTINE -
Dexamethasone PO - 4-8 mg :: PO :: BID :: 4-8 mg BID × 1-2 weeks, then taper Same Same - STAT ROUTINE -
Greater occipital nerve block (GON block) - - 2 mL :: - :: - :: Lidocaine 2% (2 mL) + triamcinolone 40 mg or methylprednisolone 40 mg; inject ipsilateral or bilateral Anticoagulation, local infection May provide 2-4 weeks relief - ROUTINE ROUTINE -
Suboccipital steroid injection - - N/A :: - :: once :: Similar to GON block; ipsilateral Same Same - ROUTINE ROUTINE -
DHE protocol (inpatient) (CPT 96365) IV - 0.5-1 mg :: IV :: q8h :: DHE 0.5-1 mg IV q8h × 3-5 days (with antiemetic pretreatment) CAD, CVA, uncontrolled HTN, triptans <24h BP, nausea, peripheral vasoconstriction - STAT - -

3C. Preventive Therapy - First-Line

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Verapamil PO - 80 mg :: PO :: TID :: Start 80 mg TID; increase by 80 mg q1-2 weeks to 240-960 mg/day in divided doses (some patients need >480 mg/day) Heart block (2nd/3rd degree), sick sinus, severe LV dysfunction, WPW ECG at baseline, after each dose increase; PR interval (hold if >280 ms) - ROUTINE ROUTINE -
Lithium PO - 300 mg :: PO :: BID :: Start 300 mg BID-TID; target serum level 0.6-1.0 mEq/L; usual dose 600-1200 mg/day Renal impairment, thyroid disease, dehydration, sodium depletion Lithium level, renal function, TSH q3-6 months - ROUTINE ROUTINE -

3D. Preventive Therapy - Second-Line

Treatment Route Indication Dosing Pre-Treatment Requirements Contraindications Monitoring ED HOSP OPD ICU
Topiramate PO - 25 mg :: PO :: daily :: Start 25 mg daily; titrate to 100-200 mg/day - Kidney stones, glaucoma, pregnancy Cognitive effects, paresthesias, metabolic acidosis - ROUTINE ROUTINE -
Melatonin PO - 9-10 mg :: PO :: QHS :: 9-10 mg QHS (higher than sleep doses) - None significant Sedation - - ROUTINE -
Galcanezumab (CGRP mAb) SC - 300 mg :: SC :: monthly :: 300 mg SC monthly (FDA approved for episodic CH) - Hypersensitivity Injection site reactions - - ROUTINE -
Valproate PO - 500-2000 mg/day :: PO :: - :: 500-2000 mg/day in divided doses - Pregnancy, hepatic disease LFTs, ammonia - ROUTINE ROUTINE -
Gabapentin PO - 900-3600 mg/day :: PO :: - :: 900-3600 mg/day; limited evidence - Renal impairment Sedation - ROUTINE ROUTINE -
Ergotamine (prophylactic) - - 1-2 mg :: PO :: - :: 1-2 mg at bedtime if nocturnal attacks - Same as DHE Limited to <2 weeks to avoid overuse - - ROUTINE -

3E. Refractory Chronic Cluster Headache

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Combination verapamil + lithium - - N/A :: - :: per protocol :: Use both at therapeutic doses Per individual agents Per individual agents - ROUTINE ROUTINE -
OnabotulinumtoxinA - - N/A :: - :: per protocol :: Off-label; pericranial injections Infection at site Limited evidence - - EXT -
Occipital nerve stimulation (ONS) - - N/A :: - :: continuous :: Implantable device; for refractory cases Poor surgical candidate Specialist decision - - EXT -
Sphenopalatine ganglion stimulation - - N/A :: - :: continuous :: Implantable device (Pulsante) Poor surgical candidate Specialist decision - - EXT -
Deep brain stimulation (hypothalamus) - - N/A :: - :: continuous :: Research settings; highly refractory Multiple Specialist decision - - EXT -

4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation ED HOSP OPD ICU Indication
Headache specialist/Neurology - ROUTINE ROUTINE - All patients; diagnosis confirmation and management
Cardiology - ROUTINE ROUTINE - Before high-dose verapamil if cardiac history
Pain management - - ROUTINE - Refractory cases, nerve block expertise
Neurosurgery - - EXT - Neuromodulation candidacy (ONS, DBS)
Home oxygen supply - ROUTINE ROUTINE - Arrange high-flow O2 for home use
Psychiatry - - ROUTINE - Depression, suicide risk (cluster headache has high depression rate)

4B. Patient/Family Instructions

Recommendation ED HOSP OPD
Oxygen therapy is FIRST-LINE for acute attacks - keep tank accessible ROUTINE ROUTINE ROUTINE
Sumatriptan SC auto-injector for breakthrough attacks; do not exceed 2/day ROUTINE ROUTINE ROUTINE
Avoid alcohol during cluster periods (potent trigger) ROUTINE ROUTINE ROUTINE
Avoid napping or irregular sleep schedules (can trigger attacks) - ROUTINE ROUTINE
Attacks often occur at same time daily (circadian pattern) - prepare - ROUTINE ROUTINE
Do NOT use over-the-counter pain medications (ineffective, risk of MOH) ROUTINE ROUTINE ROUTINE
Cluster periods may be seasonal - anticipate and start preventive early - - ROUTINE
Depression is common; seek help if mood changes - ROUTINE ROUTINE
Clusterbusters.org and headache support groups for resources - - ROUTINE

4C. Lifestyle & Prevention

Recommendation ED HOSP OPD
Complete alcohol abstinence during cluster periods ROUTINE ROUTINE ROUTINE
Maintain regular sleep schedule; avoid naps - ROUTINE ROUTINE
Avoid high altitudes during cluster periods - - ROUTINE
Avoid vasodilators (nitroglycerin, sildenafil) during cluster periods - ROUTINE ROUTINE
Avoid strong smells (perfumes, solvents) during cluster periods - ROUTINE ROUTINE
Smoking cessation (association with cluster headache) - ROUTINE ROUTINE
Keep headache diary to identify patterns and triggers - ROUTINE ROUTINE

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis Key Distinguishing Features Tests to Differentiate
Migraine Longer duration (4-72h), bilateral possible, photophobia/phonophobia, prefers rest vs restlessness Clinical criteria (ICHD-3)
Paroxysmal hemicrania Shorter attacks (2-30 min), higher frequency (>5/day), ABSOLUTE response to indomethacin Indomethacin trial (completely responsive)
SUNCT/SUNA Very short attacks (1-600 sec), very high frequency, conjunctival injection/tearing Clinical criteria; shorter duration
Hemicrania continua Continuous baseline pain with exacerbations, responds to indomethacin Indomethacin trial
Trigeminal neuralgia Electric shock-like, seconds duration, triggered by touch/chewing MRI for neurovascular compression; much shorter attacks
Pituitary tumor Visual field deficits, hormonal abnormalities, progressive MRI pituitary
Cavernous sinus lesion Persistent symptoms, cranial nerve palsies MRI/MRA
Giant cell arteritis Age >50, jaw claudication, scalp tenderness, elevated ESR ESR/CRP, temporal artery biopsy
Primary stabbing headache Brief (seconds), random location, no autonomic features Clinical

6. MONITORING PARAMETERS

Parameter ED HOSP OPD ICU Frequency Target/Threshold Action if Abnormal
Attack frequency/severity diary ROUTINE ROUTINE ROUTINE - Daily during bout Decreasing frequency Adjust preventive
ECG (verapamil patients) - STAT ROUTINE - Baseline, after each dose increase PR <280 ms, no AV block Hold/reduce verapamil
Lithium level - ROUTINE ROUTINE - Weekly until stable, then q3 months 0.6-1.0 mEq/L Adjust dose
Renal function (lithium) - ROUTINE ROUTINE - q3-6 months Stable May need to discontinue
TSH (lithium) - - ROUTINE - q6 months Normal Lithium-induced hypothyroidism
Blood pressure ROUTINE ROUTINE ROUTINE - Each visit Normal Adjust verapamil
Depression screening - ROUTINE ROUTINE - Each visit Negative Refer psychiatry

7. DISPOSITION CRITERIA

Disposition Criteria
Discharge from ED Attack aborted with O2/triptan, preventive medication initiated or adjusted, home O2 arranged, follow-up planned
Admit to hospital Severe refractory attacks, need for IV DHE protocol, unable to manage at home, new diagnosis requiring workup
Headache specialist referral All patients; chronic cluster, refractory cases, neuromodulation consideration
Urgent follow-up Within 1-2 weeks if in active cluster period

8. EVIDENCE & REFERENCES

Recommendation Evidence Level Source
High-flow oxygen effective for acute cluster Class I, Level A Multiple RCTs; Cochrane Reviews
Sumatriptan SC effective for acute cluster Class I, Level A Multiple RCTs
Verapamil effective for prevention Class I, Level A Multiple RCTs
Lithium effective for chronic cluster Class II, Level B RCTs with limitations
Corticosteroids effective for transitional therapy Class II, Level B Multiple studies
Greater occipital nerve block effective Class II, Level B Multiple studies
Galcanezumab approved for episodic CH Class I, Level A FDA approved 2019; GAAIN trial (Goadsby et al., NEJM 2019)
Indomethacin response distinguishes paroxysmal hemicrania Class I Diagnostic criterion

NOTES

  • Cluster headache is one of the most severe pain conditions known ("suicide headache")
  • Attacks have striking circadian and circannual periodicity
  • Oxygen is FIRST-LINE abortive - very effective, no cardiovascular contraindications
  • Sumatriptan SC is preferred over oral (onset too slow for short attacks)
  • Verapamil is mainstay preventive; requires ECG monitoring for PR prolongation at higher doses
  • Alcohol is a potent trigger DURING cluster period but not during remission
  • Depression and suicidal ideation are common - screen actively
  • Transitional therapy (steroids/GON block) provides bridge while preventive takes effect
  • Galcanezumab (CGRP mAb) is FDA-approved for episodic cluster headache
  • Distinguish from paroxysmal hemicrania (absolute indomethacin response) - trial if uncertain

CHANGE LOG

v1.0 (January 29, 2026) - Initial template creation - ICHD-3 diagnostic criteria included - Acute, transitional, and preventive treatment tiers - Galcanezumab (FDA-approved CGRP mAb) included - Oxygen emphasized as first-line abortive - Depression screening emphasized