Headache: A Merck Manual of Patient Symptoms podcast

Cluster headaches cause excruciating, unilateral periorbital or temporal pain, with ipsilateral autonomic symptoms (ptosis, lacrimation, rhinorrhea, nasal congestion). Diagnosis is clinical. Acute treatment is with parenteral triptans, dihydroergotamine, or O₂. Prevention is with verapamil, lithium, topiramate, divalproex, or a combination.

Cluster headache affects primarily men, typically beginning at age 20 to 40; prevalence in the US is 0.4%. Usually, cluster headache is episodic; for 1 to 3 mo, patients experience ≥ 1 attack/day, followed by remission for months to years. Some patients have cluster headaches without remission.

Pathophysiology is unknown, but the periodicity suggests hypothalamic dysfunction. Alcohol intake triggers cluster headache during the attack period but not during remission.

Symptoms and Signs

Symptoms are distinctive. Attacks usually occur at the same time each day, often awakening patients from sleep. Pain is always unilateral in an orbitotemporal distribution. It is excruciating, peaking within minutes; it usually subsides spontaneously within 30 min to 1 h. Patients are agitated, restlessly pacing the floor, unlike migraine patients who prefer to lie quietly in a darkened room.

Autonomic features, including nasal congestion, rhinorrhea, lacrimation, facial flushing, and Horner syndrome, are prominent and usually occur on the same side as the headache.

Diagnosis

• Clinical evaluation

Diagnosis is based on the distinctive symptom pattern and exclusion of intracranial abnormalities.

Other unilateral primary headache syndromes with autonomic symptoms should be excluded:

• SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing): Attacks are very brief (5 to 250 sec) and occur at high frequency (up to 200 attacks/day).
• Chronic paroxysmal hemicrania: Attacks are more frequent (> 5/day) and much briefer (usually just minutes) than in cluster headache.
• Hemicrania continua: Moderately severe continuous unilateral head pain occurs with superimposed brief episodes of more intense pain.

Chronic paroxysmal hemicrania and hemicrania continua, unlike SUNCT and cluster headache (and migraine), respond dramatically to indomethacinSome Trade Names
INDOCIN
Click for Drug Monograph
, but not to other NSAIDs.

Treatment

• For aborting attacks, parenteral triptans, dihydroergotamineSome Trade Names
  D.H.E. 45
  MIGRANAL
  Click for Drug Monograph
  , or 100% O₂
• For long-term prophylaxis, verapamilSome Trade Names
  CALAN
  ISOPTIN
  Click for Drug Monograph
  , lithiumSome Trade Names
  ESKALITH
  LITHOBID
  LITHONATE
  Click for Drug Monograph
  , topiramateSome Trade Names
  TOPAMAX
  Click for Drug Monograph
  , divalproexSome Trade Names
  DEPAKOTE
  Click for Drug Monograph
  , or a combination

Acute attacks of cluster headache can be aborted with either a parenteral triptan or dihydroergotamineSome Trade Names
D.H.E. 45
MIGRANAL
Click for Drug Monograph
(see see Headache: Drugs for Migraine and Cluster Headaches*) and/or 100% O₂ inhalation given by nonrebreathing face mask.

All patients require preventive drugs because cluster headache is frequent, severe, and incapacitating. PrednisoneSome Trade Names
DELTASONE
Click for Drug Monograph
(eg, 60 mg po once/day) or a greater occipital nerve block (with a local anesthetic and a corticosteroid) can provide prompt temporary prevention while preventive drugs with slower onset of action (eg, verapamilSome Trade Names
CALAN
ISOPTIN
Click for Drug Monograph
, lithiumSome Trade Names
ESKALITH
LITHOBID
LITHONATE
Click for Drug Monograph
, topiramateSome Trade Names
TOPAMAX
Click for Drug Monograph
, divalproexSome Trade Names
DEPAKOTE
Click for Drug Monograph
) are initiated.

Table 4
PrintOpen table in new window
Drugs for Migraine and Cluster Headaches* Drug Dosage Comments Prevention AmitriptylineSome Trade Names ELAVIL ENDEP Click for Drug Monograph 10–100 mg po at bedtime Used only for migraines Has anticholinergic effects; causes weight gain Helpful for patients with insomnia Small doses often effective β-Blockers AtenololSome Trade Names TENORMIN Click for Drug Monograph 25–100 mg po once/day MetoprololSome Trade Names LOPRESSOR TOPROL Click for Drug Monograph 50–200 mg po once/day NadololSome Trade Names CORGARD Click for Drug Monograph 20–160 mg po once/day PropranololSome Trade Names INDERAL Click for Drug Monograph 20–160 mg po bid TimololSome Trade Names BLOCADREN TIMOPTIC Click for Drug Monograph 5–20 mg po once/day Used only for migraines Only β-blockers without intrinsic sympathomimetic activity used Avoided in patients with bradycardia, hypotension, or asthma DivalproexSome Trade Names DEPAKOTE Click for Drug Monograph Regular-release: 250–500 mg po bid Extended-release: 500–1000 mg po once/day Can cause alopecia, GI upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph 300 mg po bid to qid Used only for cluster headaches May cause weakness, thirst, tremor, and polyuria Periodic checking of drug levels required OnabotulinumtoxinA — Considered 2nd-line treatment TopiramateSome Trade Names TOPAMAX Click for Drug Monograph 50–200 mg po usually once/day Can cause weight loss and CNS adverse effects (eg, confusion, depression) VerapamilSome Trade Names CALAN ISOPTIN Click for Drug Monograph † 240 mg once/day to tid Most useful for patients with cluster headache Can cause hypotension and constipation Treatment DihydroergotamineSome Trade Names D.H.E. 45 MIGRANAL Click for Drug Monograph 0.5–1 mg sc or IV 4 mg/mL nasal spray Can cause nausea Contraindicated in patients with hypertension or coronary artery disease Cannot be used concurrently with triptans Pulmonary-inhaled formulation under development Triptans‡ AlmotriptanSome Trade Names AXERT Click for Drug Monograph 12.5 mg po EletriptanSome Trade Names RELPAX Click for Drug Monograph 20–40 mg po FrovatriptanSome Trade Names FROVA Click for Drug Monograph 2.5 mg po NaratriptanSome Trade Names AMERGE Click for Drug Monograph 2.5 mg po RizatriptanSome Trade Names MAXALT Click for Drug Monograph 10 mg po SumatriptanSome Trade Names IMITREX Click for Drug Monograph 50–100 mg po, 5–20 mg nasal spray, or 6 mg sc ZolmitriptanSome Trade Names ZOMIG Click for Drug Monograph 2.5–5 mg po or 5 mg nasal spray Can cause flushing, paresthesias, and sense of pressure in chest or throat Can repeat doses up to 3 times/day if headache recurs Contraindicated in patients with coronary artery disease, uncontrolled hypertension, hemiplegic migraine, or intracranial vascular disease Injections or nasal spray used for cluster headache ValproateSome Trade Names DEPAKENE Click for Drug Monograph 500–1000 mg IV Usually for patients who cannot tolerate triptans or vasoconstrictors With long-term use, can cause alopecia, GI upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain *Drugs can be used for either type of headache unless specified otherwise. †The regular-release formulation is usually used. ‡Triptans are given once, then repeated as needed. Drugs for Migraine and Cluster Headaches* Drug Dosage Comments Prevention AmitriptylineSome Trade Names ELAVIL ENDEP Click for Drug Monograph 10–100 mg po at bedtime Used only for migraines Has anticholinergic effects; causes weight gain Helpful for patients with insomnia Small doses often effective β-Blockers AtenololSome Trade Names TENORMIN Click for Drug Monograph 25–100 mg po once/day MetoprololSome Trade Names LOPRESSOR TOPROL Click for Drug Monograph 50–200 mg po once/day NadololSome Trade Names CORGARD Click for Drug Monograph 20–160 mg po once/day PropranololSome Trade Names INDERAL Click for Drug Monograph 20–160 mg po bid TimololSome Trade Names BLOCADREN TIMOPTIC Click for Drug Monograph 5–20 mg po once/day Used only for migraines Only β-blockers without intrinsic sympathomimetic activity used Avoided in patients with bradycardia, hypotension, or asthma DivalproexSome Trade Names DEPAKOTE Click for Drug Monograph Regular-release: 250–500 mg po bid Extended-release: 500–1000 mg po once/day Can cause alopecia, GI upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph 300 mg po bid to qid Used only for cluster headaches May cause weakness, thirst, tremor, and polyuria Periodic checking of drug levels required OnabotulinumtoxinA — Considered 2nd-line treatment TopiramateSome Trade Names TOPAMAX Click for Drug Monograph 50–200 mg po usually once/day Can cause weight loss and CNS adverse effects (eg, confusion, depression) VerapamilSome Trade Names CALAN ISOPTIN Click for Drug Monograph † 240 mg once/day to tid Most useful for patients with cluster headache Can cause hypotension and constipation Treatment DihydroergotamineSome Trade Names D.H.E. 45 MIGRANAL Click for Drug Monograph 0.5–1 mg sc or IV 4 mg/mL nasal spray Can cause nausea Contraindicated in patients with hypertension or coronary artery disease Cannot be used concurrently with triptans Pulmonary-inhaled formulation under development Triptans‡ AlmotriptanSome Trade Names AXERT Click for Drug Monograph 12.5 mg po EletriptanSome Trade Names RELPAX Click for Drug Monograph 20–40 mg po FrovatriptanSome Trade Names FROVA Click for Drug Monograph 2.5 mg po NaratriptanSome Trade Names AMERGE Click for Drug Monograph 2.5 mg po RizatriptanSome Trade Names MAXALT Click for Drug Monograph 10 mg po SumatriptanSome Trade Names IMITREX Click for Drug Monograph 50–100 mg po, 5–20 mg nasal spray, or 6 mg sc ZolmitriptanSome Trade Names ZOMIG Click for Drug Monograph 2.5–5 mg po or 5 mg nasal spray Can cause flushing, paresthesias, and sense of pressure in chest or throat Can repeat doses up to 3 times/day if headache recurs Contraindicated in patients with coronary artery disease, uncontrolled hypertension, hemiplegic migraine, or intracranial vascular disease Injections or nasal spray used for cluster headache ValproateSome Trade Names DEPAKENE Click for Drug Monograph 500–1000 mg IV Usually for patients who cannot tolerate triptans or vasoconstrictors With long-term use, can cause alopecia, GI upset, hepatic dysfunction, thrombocytopenia, tremor, and weight gain *Drugs can be used for either type of headache unless specified otherwise. †The regular-release formulation is usually used. ‡Triptans are given once, then repeated as needed.

Key Points

• Typically, cluster headache causes excruciating unilateral periorbital or temporal pain, with ipsilateral ptosis, lacrimation, rhinorrhea, and/or nasal congestion, in men aged 20 to 40 yr.
• Usually, patients experience ≥ 1 attack/day for 1 to 3 mo, followed by remission for months to years.
• Diagnose cluster headache based on clinical findings.
• To abort attacks, give a parenteral triptan or dihydroergotamineSome Trade Names
  D.H.E. 45
  MIGRANAL
  Click for Drug Monograph
  (see Table 4: Headache: Drugs for Migraine and Cluster Headaches*) and/or 100% O₂ inhalation by a nonrebreathing face mask.
• To prevent attacks, use prednisoneSome Trade Names
  DELTASONE
  Click for Drug Monograph
  or a greater occipital nerve block for short-term relief and verapamilSome Trade Names
  CALAN
  ISOPTIN
  Click for Drug Monograph
  , lithiumSome Trade Names
  ESKALITH
  LITHOBID
  LITHONATE
  Click for Drug Monograph
  , topiramateSome Trade Names
  TOPAMAX
  Click for Drug Monograph
  , and/or divalproexSome Trade Names
  DEPAKOTE
  Click for Drug Monograph
  for long-term relief.

short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare headache disorder characterized by extremely frequent attacks of unilateral head pain and autonomic activation.

SUNCT, like cluster headache, is a primary headache disorder characterized by unilateral pain in the trigeminal nerve distribution and by autonomic manifestations. As such, SUNCT and cluster headaches are sometimes grouped together as trigeminal autonomic cephalgias.

In SUNCT, pain paroxysms are typically periorbital, are extremely frequent (up to 200/day), and last from 5 to 250 sec. Conjunctival injection is often the most prominent autonomic feature; tearing may also be obvious.

Diagnosis

Diagnosis is clinical. SUNCT should be distinguished from trigeminal neuralgia, which causes similar symptoms; SUNCT differs in that

• It has no refractory period.
• Pain occurs predominantly in the ophthalmic division of the trigeminal nerve.
• Attacks are not triggered by cutaneous stimuli.
• IndomethacinSome Trade Names
  INDOCIN
  Click for Drug Monograph
  does not relieve symptoms, as it does in some other headache disorders.

Treatment

Treatment can include IV lidocaineSome Trade Names
XYLOCAINE
Click for Drug Monograph
for acute attacks and, for prevention, anticonvulsants (eg, lamotrigineSome Trade Names
LAMICTAL
Click for Drug Monograph
, topiramateSome Trade Names
TOPAMAX
Click for Drug Monograph
, gabapentinSome Trade Names
NEURONTIN
Click for Drug Monograph
) and occipital nerve stimulation or blockade.

Last full review/revision November 2012 by Stephen D. Silberstein, MD

Content last modified December 2012