Cluster headache

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Cluster headache is a trigeminal autonomic cephalalgia defined by attack geometry. Pain is severe or very severe, always unilateral around the eye or temple for a given attack, and reaches full intensity quickly. Untreated attacks last 15–180 minutes and can occur up to eight times daily, frequently waking the patient from sleep. Ipsilateral cranial autonomic activation produces a red watering eye, nasal congestion or discharge, eyelid swelling, facial sweating, miosis or ptosis. Some patients show marked restlessness without an obvious autonomic sign. Alcohol can trigger attacks during an active bout but not necessarily in remission; this pattern is more useful than a universal trigger list. Episodic cluster headache has remission periods, whereas chronic cluster headache has no remission or only brief remission over the relevant classification period.

Differentiate migraine by duration, movement behaviour and autonomic prominence. Migraine usually lasts longer and activity worsens pain, encouraging stillness, although unilateral tearing can occur. Paroxysmal hemicrania produces shorter, more frequent attacks with an absolute indomethacin response; SUNCT or SUNA produces attacks lasting seconds to minutes. Trigeminal neuralgia causes electric-shock facial pain triggered by innocuous stimuli and usually lacks the longer orbital-autonomic attack. Acute angle closure causes eye signs and visual impairment requiring ophthalmic emergency care. A painful persistent partial Horner syndrome or neck pain raises arterial dissection. Pituitary and other structural lesions can mimic a trigeminal autonomic cephalalgia, so a first bout merits experienced review of imaging need rather than automatic reassurance.

Attack treatment must act within minutes. NICE recommends high-flow 100% oxygen and/or a nasal or subcutaneous triptan, chosen for access, contraindications and patient preference. Oral drugs are too slow. Oxygen needs correct equipment, fire and smoking counselling, and an arrangement that works outside the home; a concentrator unable to provide the required flow is not equivalent. Sumatriptan injection is rapid but daily attack frequency, dose limits and cardiovascular contraindications may constrain use. Preventive treatment begins promptly because bouts can generate multiple attacks daily. Verapamil is commonly first line, but doses used in cluster headache may exceed routine cardiovascular prescribing and can cause PR prolongation or heart block; specialist-led titration with baseline and repeat ECG is essential. A short transitional corticosteroid course or greater occipital nerve block may be used by an experienced service while prevention takes effect, with local regimens and contraindications guiding choice.

Key points

Cluster headache causes excruciating strictly unilateral orbital, supraorbital or temporal pain lasting 15–180 minutes when untreated, often at a strikingly similar time each day.
Attacks occur from one every other day up to eight daily and cluster into bouts lasting weeks or months, separated by remission in episodic disease.
At least one ipsilateral autonomic feature—tearing, conjunctival injection, nasal blockage, rhinorrhoea, eyelid oedema, sweating, miosis or ptosis—or marked restlessness accompanies the pain.
Patients tend to pace or rock and cannot keep still, unlike many people with migraine who withdraw from movement; this behavioural distinction is diagnostically valuable.
Offer 100% oxygen at a flow rate of at least 12 litres per minute through a non-rebreathing mask and/or a subcutaneous or nasal triptan for acute attacks.
Do not offer paracetamol, NSAIDs, opioids, ergots or oral triptans for acute cluster headache because onset is too rapid or the harm-benefit balance is unfavourable.
When oxygen is prescribed, arrange both stationary and ambulatory equipment where appropriate and ensure a non-rebreathing mask rather than ordinary nasal cannulae.
Consider verapamil during a cluster bout, seeking specialist advice for dose escalation and ECG monitoring; initial and serial conduction checks are central to safe use.
Discuss neuroimaging with a clinician experienced in headache for a first bout, and reassess established disease if side, duration, neurology or autonomic findings change.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Primary neurovascular susceptibility

Cluster headache is a primary trigeminal autonomic cephalalgia defined clinically by severe unilateral orbital or temporal attacks with autonomic features or marked restlessness.

Bout-related triggers

Alcohol can trigger attacks during an active cluster bout but not necessarily during remission, so exposure acts as a trigger rather than an underlying cause.

Secondary cluster-like syndromes

Pituitary, posterior-fossa, orbital and vascular lesions can rarely produce a similar phenotype, particularly at first presentation or when the pattern changes.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Circadian attack pattern
Attacks often occur at a strikingly similar time each day and cluster into bouts separated by remission in episodic disease.
2
Trigeminal pain activation
Activation of first-division trigeminal afferents produces severe unilateral orbital, supraorbital or temporal pain and sensitises cranial pain pathways.
3
Cranial autonomic reflex
Trigeminal input activates parasympathetic outflow and alters sympathetic tone, producing tearing, conjunctival injection, nasal symptoms, eyelid oedema, miosis or ptosis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Orbital clockwork pain

Very severe unilateral orbital, supraorbital or temporal pain recurring at similar circadian times for 15–180 minutes strongly suggests cluster headache.

Ipsilateral autonomic activation

Tearing, red eye, rhinorrhoea, nasal blockage, eyelid oedema, facial sweating, miosis or ptosis occurs on the pain side during attacks.

Restless behaviour

Pacing, rocking or pressing the head while unable to lie still is characteristic and contrasts with the movement avoidance common during migraine.

Bout periodicity

Daily attacks over weeks with later remission support episodic cluster headache, while absent or very short remissions suggest a chronic pattern needing specialist care.

Painful persistent Horner syndromeRed flag

Ptosis and miosis persisting outside attacks, especially with new neck pain, should prompt urgent assessment for carotid dissection or another sympathetic-pathway lesion.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Attack-duration and frequency diaryFirst step
Why
Demonstrate the stereotyped timing, autonomic accompaniments, triggers, treatment response and bout boundaries.
Interpretation and limitations
Repeated 15–180-minute attacks with ipsilateral signs fit cluster; consistently shorter attacks should reopen the wider trigeminal-autonomic differential.
02
Neurological, pupillary and ocular examination
Why
Confirm that transient autonomic findings resolve and identify persistent deficit, Horner syndrome or an eye emergency.
Interpretation and limitations
Examination may be normal between attacks; fixed anisocoria, reduced vision, ophthalmoplegia or focal neurology requires urgent secondary investigation.
03
Specialist-directed MRI brain and pituitary region
Why
Exclude a structural mimic in a first bout or atypical trigeminal-autonomic presentation.
Interpretation and limitations
Imaging choice follows specialist assessment; a lesion's relevance must be judged against phenotype rather than assuming every incidental pituitary finding is causal.
04
Baseline and serial 12-lead ECG
Why
Detect PR prolongation, bradycardia or conduction block before and during verapamil titration.
Interpretation and limitations
Do not escalate through a conduction abnormality; repeat timing follows the specialist protocol, particularly after dose increments and with interacting medicines.
05
Blood pressure and cardiovascular history
Why
Assess suitability for triptan rescue and monitor verapamil-related hypotension or bradycardia.
Interpretation and limitations
Established arterial disease or uncontrolled hypertension may exclude triptans, while low pressure or conduction disease can narrow preventive choices.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Migraine

Longer attacks with nausea, sensory sensitivity and preference for stillness favour migraine; marked pacing, short stereotyped episodes and ipsilateral autonomic signs support cluster headache.

Other trigeminal autonomic cephalalgias

Much shorter frequent attacks or a continuous unilateral background and a specific indometacin response suggest paroxysmal hemicrania, SUNCT, SUNA or hemicrania continua.

Trigeminal neuralgia

Brief electric-shock pain triggered by touch or chewing, with little sustained restlessness, favours neuralgia; prominent autonomic signs can nevertheless cause overlap.

Secondary orbital, pituitary or vascular disease

New neurological or endocrine signs, atypical duration, changing side or persistent background pain should prompt specialist-directed imaging rather than reliance on phenotype alone.

Additional chapter-specific clues

Ocular mimicRed flag

A persistently red painful eye, reduced acuity, cloudy cornea, fixed pupil or ongoing vomiting is not safely attributed to cluster headache and needs urgent ophthalmic assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01AttackDeliver treatment within minutesFirst stepA typical cluster attack begins in a person with a secure diagnosis.

1Use 100% oxygen at at least 12 litres per minute through a reservoir non-rebreathing mask and/or the prescribed subcutaneous or nasal triptan immediately.
2Continue the agreed oxygen session and triptan limits exactly, documenting response time and avoiding repeat doses beyond the formulation maximum.
3If the attack differs in duration, eye findings, neurology or recovery, stop treating by pattern alone and arrange urgent reassessment.
4After repeated rescue use, confirm equipment function, attack frequency and preventive progress rather than substituting oral analgesics or opioids.

02New boutStart rescue and prevention togetherStereotyped attacks recur after remission or a first cluster bout is suspected.

1Confirm the attack geometry and red-flag screen, discuss first-bout imaging with a headache-experienced clinician and record baseline cardiovascular status.
2Arrange usable home and ambulatory oxygen plus an appropriate rapid triptan, including device teaching, fire safety and daily dose limits.
3Seek specialist advice to start and titrate verapamil with baseline and repeat ECG monitoring, considering a specialist transitional treatment if burden is extreme.
4Set early review because attack frequency and suicidal distress can change quickly during a bout, and prevention should not await its natural end.

03Refractory or atypicalEscalate beyond routine cluster careEscalationCorrect rescue fails, verapamil is unsafe, attacks become continuous or the phenotype no longer fits.

1Check oxygen flow and mask, injection or nasal technique, timing, triptan quantity and adherence before declaring pharmacological failure.
2Reclassify attack duration and frequency against paroxysmal hemicrania, SUNCT or SUNA, migraine, neuralgia and structural mimics.
3AlternativeArrange headache-neurology review for alternative preventives, nerve block, transitional therapy or advanced options under the commissioned pathway.
4EscalationAssess mood, sleep loss, work impact and immediate self-harm risk, offering crisis support alongside headache escalation.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides rapid non-vasoconstrictive acute treatment and can be repeated for multiple attacks when prescribed equipment is available.

High-flow medical oxygen

Use 100% oxygen at a flow of at least 12 litres per minute through a reservoir non-rebreathing mask during the attack.

Prescribe the correct cylinder, regulator and mask, arrange ambulatory supply when needed, and give strict fire and smoking safety advice; nasal cannulae are inadequate.

A very rapid triptan rescue option suited to the short time course and extreme severity of cluster attacks.

Sumatriptan subcutaneous

Usually 6 mg at attack onset; a second 6 mg dose may be used for a subsequent attack after at least 1 hour, maximum two doses in 24 hours.

Avoid with relevant coronary, cerebrovascular or peripheral arterial disease and uncontrolled hypertension; severe hepatic impairment is contraindicated, and renal or mild-to-moderate hepatic impairment requires product-specific caution. Check interacting triptans or ergots and daily attack burden.

A rapid non-oral alternative when injection is unacceptable and the nasal route can be used correctly.

Sumatriptan nasal

Usually 20 mg into one nostril at onset; one further dose may be used for a subsequent attack after at least 2 hours, maximum 40 mg in 24 hours.

Shares triptan vascular contraindications and severe hepatic impairment is contraindicated; use product-specific caution in mild-to-moderate hepatic or renal impairment. It may be too slow for some attacks, and high-frequency bouts must not drive exposure beyond the formulation limit.

The principal bout preventive considered by NICE, reducing attack frequency while the active cluster period continues.

Verapamil

Initiate and titrate only with specialist advice using the local cluster-headache regimen, baseline ECG and repeat ECG after dose increases.

Can cause bradycardia, PR prolongation, heart block, hypotension, constipation and interactions; cluster doses demand structured cardiac surveillance and pregnancy-specific advice.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Severe psychological distress

Repeated excruciating attacks can cause panic, depression and suicidal thinking, making direct risk assessment and rapid access to effective rescue treatment important.

Sleep and occupational disruption

Nocturnal and repeated daytime attacks fragment sleep, impair concentration and can make driving or hazardous work unsafe during a bout.

Treatment-related harm

Frequent triptan exposure and preventive medicines can create cardiovascular, conduction or interaction risks, while unsuitable oral analgesics delay useful care without controlling attacks.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record daily attack count, untreated duration, autonomic signs, rescue used and time to relief so bout trajectory and treatment performance remain visible.
Obtain baseline and protocol-timed ECGs during verapamil titration, and ask about syncope, dizziness, bradycardia, breathlessness and constipation.
Review oxygen equipment, prescribed flow, mask seal, cylinder capacity, portability and fire safety rather than asking only whether oxygen was tried.
Track subcutaneous and nasal triptan doses across each 24-hour period, especially when attacks occur several times daily.
Ask directly about sleep deprivation, depression, unbearable distress and suicidal thinking during active bouts, escalating mental-health risk immediately.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Behaviour separates phenotypes

The patient pacing in desperation contrasts with migraine-related stillness; observing what movement does to the person can be as useful as pain adjectives.

Equipment is part of the prescription

Writing 'oxygen' without flow, regulator, reservoir mask and practical supply can create an ineffective treatment despite the correct drug concept.

Ptosis should switch off

Autonomic signs generally accompany the attack. A new Horner syndrome persisting between episodes deserves assessment for carotid or cavernous-pathway disease.

ECG surveillance is dynamic

A normal baseline trace does not license unrestricted verapamil escalation because conduction delay may appear after dose increases or with interacting medicines.

First bout deserves reflection

A compelling cluster phenotype remains clinical, but structural mimics justify headache-experienced consideration of imaging at first presentation or when features become atypical.

11Common pitfallsFrequent interpretation and management errors.

01
Treating cluster headache with oral paracetamol, NSAIDs or oral triptans that cannot match the speed and severity of the attack.
02
Prescribing low-flow oxygen through nasal cannulae or an unsuitable concentrator and recording the resulting failure as oxygen resistance.
03
Starting or escalating verapamil without specialist dosing advice and serial ECG monitoring for potentially dangerous conduction effects.
04
Assuming every red watering eye with headache is cluster and missing acute glaucoma, inflammation, infection or a fixed neurological lesion.
05
Overlooking persistent Horner syndrome outside the attack because transient ptosis and miosis can be part of cluster headache.
06
Focusing only on pain frequency while failing to assess severe sleep loss, occupational collapse and suicidal distress during a bout.