FIRST CONSULT  

Cluster headache
Revised: October 14, 2013
Copyright Elsevier BV. All rights reserved.

Key points
Cluster headaches are recurrent episodes of excruciatingly severe, unilateral
headache/facial pain

Patients usually present with intense, penetrating or boring pain that is typically
localized in the periorbital area and temple. Cluster headaches are often associated
with ipsilateral autonomic nervous system dysfunction such as tearing, sweating, and
miosis

Temporal cyclicity is characteristic; each headache is short-lived (usually less than 1

hour) but may occur at the same time(s) each day for weeks or months at a time, then
abruptly stop

Diagnosis is largely based on history and clinical features; diagnostic tests are
performed to rule out alternate diagnoses

Patients should avoid known triggers such as alcohol, bright lights and glare, sleep
deprivation, and stress

Acute treatments such as triptans and ergotamines are available to shorten the
cluster period or prevent anticipated attacks but may not be effective in all patients.
In the clinic or hospital setting, 100% oxygen via face mask may abort the attack

Prophylactic treatments are also available; these are important because of the limited
usefulness of abortive agents and the intense nature of the pain

Cluster headache is a self-limiting condition; symptoms may eventually subside

spontaneously, usually after a number of years, with no long-lasting or serious effects

Background
Description
Recurrent episodes of excruciatingly severe unilateral headache/facial pain

Rapid onset of headache without warning; pain is often localized in periorbital

area and temple
 Unlike migraine, cluster headache sufferers do not lie flat or remain still. Instead,
they usually pace, rock, or walk outdoors during headaches. They may isolate
themselves

Can last 15 to 180 minutes, although most attacks are less than 1 hour's duration;
can occur up to eight times per day

During a cluster period, attacks often assume temporal cyclicity with attacks at
almost the same time each day. Headache typically begins a few hours after the
patient goes to bed or while relaxing after work in the late afternoon

Associated with one or more autonomic nervous system dysfunctions on the side
experiencing pain: tearing, red eye, puffy eyelid, stuffy/runny nose, facial
sweating, ptosis, miosis

Occurs in two forms:

Episodic
Approximately 80% of patients

Attack phases last 2 to 16 weeks, followed by a cluster-free interval of 6

months to several years

Chronic
Approximately 20% of patients

No sustained cluster-free intervals

The condition usually subsides with no long-term consequences

Epidemiology
Incidence and prevalence

Cluster headache affects approximately 200 persons per 100,000

Demographics

Age:

Cluster headaches occur predominantly in patients aged over 30 years

Gender:

The male-to-female ratio is 4:1

Genetics:

Higher frequency of cluster headache among families

To date no specific genes have been identified, but inheritance is likely to be

autosomal dominant with low penetrance; there might be autosomal recessive or
 multifactorial inheritance

Causes and risk factors

Causes:

Etiology unknown for the cause of cluster headache or its associated autonomic
dysfunction

Possible relationship to previous head trauma or surgery

Contributory or predisposing factors:

Alcohol

Vasodilators ( eg , nitroglycerin)

Sleep disorders such as insomnia, narcolepsy, and obstructive sleep apnea

Changes in barometric pressure

Chronic tobacco use

Male gender

Age over 30 years

Family history of cluster headaches. Genetic factors may contribute, but to date no
specific gene has been identified

Screening
Summary approach
Not applicable.

Primary prevention
Summary approach
Not applicable.

Diagnosis
Summary approach
Sudden onset of severe headache, reaching a crescendo within 15 minutes and
lasting 30 to 180 minutes (although most attacks are less than 1 hour's duration);
can occur one to eight times per day

Attacks may occur at the same time on consecutive days; frequently an attack
occurs within 90 minutes of falling asleep, corresponding to first rapid eye
 movement (REM) sleep

Headache may be episodic (with attack phases lasting 2 to 16 weeks followed by a

cluster-free interval of 6 months to several years) or, less commonly, chronic (with
no sustained cluster-free interval)

Diagnosis is largely based on history and clinical features

Patients usually present with intense, penetrating or boring pain that is typically
localized in the periorbital area and temple

Diagnostic tests are performed to rule out alternative diagnoses

The physical examination and diagnostic tests are often normal

Clinical presentation
Symptoms

Episodes of intense, penetrating or boring pain, less often throbbing, that is

typically localized in the periorbital area and temple

Pain is unilateral, oculotemporal, or oculofrontal

Often associated with ipsilateral autonomic nervous system dysfunction:

Lacrimation

Rhinorrhea and nasal congestion

Perspiration

Facial flushing

Nausea, but not usually associated with vomiting

Patients may be restless and agitated during attacks

Other historical information

History of alcohol use; small amounts of alcohol may trigger cluster headache

Smoking history; smoking may also contribute to cluster headaches

Patients who do not see a dentist for regular checkups are more likely to have
active dental disease, which might be the cause of acute facial pain rather than
cluster headaches

Determine if there is a family history of headaches. Studies of patient relatives

have found a frequency 13 times higher than expected by chance

Signs
 Bradycardia

Tenderness of the frontotemporal region

Avoidance of immobility with pacing, stomping, or running

Ipsilateral autonomic dysfunction:

Ipsilateral partial Horner syndrome with ptosis and miosis

Conjunctival injection

Facial sweating

Eyelid edema

Other physical examination factors

Between headaches the examination is normal, although residual Horner syndrome can
be seen when the patient is examined during the headache:

If the patient looks unwell, check for localized infection and neck stiffness; exclude
serious conditions such as meningitis and subarachnoid hemorrhage

Check the patient's blood pressure and temperature. Raised blood pressure may
suggest hypertensive headache or pheochromocytoma . Raised intracranial pressure may
also present with raised blood pressure and a slow pulse

Check pupils for loss of reactivity, which suggests Horner syndrome, and corneas
for clouding, which is indicative of acute glaucoma

Papilledema suggests any cause of increased intracranial pressure, including

tumor, pseudotumor cerebri, and venous sinus thrombosis

Proptosis and orbital edema suggest cavernous sinus thrombosis

Tender swollen temporal artery suggests temporal arteritis

Acute tenderness of scalp and face is common in migraine

Facial tenderness is seen in sinusitis

Check for purulent nasal discharge. Feel the temporomandibular joint as the
patient opens and closes jaw. Crepitus is a suspicious feature; some clicking is not
unusual, but if marked it may be suggestive of dysfunction

Look at teeth for signs of bruxism

Conduct a careful and complete neurologic examination to rule out a fixed focal deficit,
which may indicate intracranial pathology:
 Test cranial nerves and check that power, tone, sensation, coordination, and
reflexes are normal in all four limbs

Look for ataxia, alteration of mental status, focal deficits, and meningeal signs

Diagnostic testing
Diagnostic tests are performed to rule out alternative diagnoses:

New onset of headache in a patient aged over 50 years, especially if accompanied

by cranial artery or scalp tenderness, requires determination of erythrocyte
sedimentation rate (ESR) (178027210_866)to check for giant cell arteritis

Complete blood count (178198746_531)is performed to exclude anemia and

hyperviscosity states

Temporal artery biopsy (178027210_405)should be considered in cases of new onset

headache in the elderly, especially if accompanied by cranial artery, scalp
tenderness, and/or elevated ESR. Biopsy is useful if within 48 hours of starting
steroids

Computed tomography (CT) scan (178027210_618)is the test of choice for emergent
detection of potentially life-threatening lesions

In patients with signs of meningeal irritation or sudden, severe headache, lumbar

puncture (178027211_896)with examination and culture of cerebrospinal fluid (CSF)
should follow CT to rule out an infectious cause or subarachnoid hemorrhage
(provided the CT scan reveals no contraindication)

Magnetic resonance imaging (MRI) (178200078_172)should be performed in cases of new

onset headache when tumor is suspected; it is less sensitive for emergent causes
such as meningitis or subarachnoid hemorrhage

Erythrocyte sedimentation rate

 

Description

The amount of sedimentation of blood diluted with sodium citrate during a 1-

hour period

Normal results

<20 mm/h in men

<25 mm/h in women

Comments

ESR increases with age; rarely, values above 50 mm/h may be normal in patients
aged over 70 years
 Marker of inflammation in the serum; measures the acute phase response to
inflammation

Used to screen for giant cell arteritis

Normal in primary headache

If results are negative, checking C-reactive protein can increase sensitivity when
temporal arteritis is suspected

May be raised in inflammation, infection, infarction, malignancy, and thyroid

disease

May be lowered in polycythemia, sickle cell disease, steroid use, and

hyperviscosity

Results can be affected by long-term steroid use and chronic inflammatory

states such as arthritis, autoimmune disease, and renal failure

Complete blood count

 

Description

Venous blood sample for quantitative and morphologic evaluation of formed

blood elements

Normal results

Leukocyte count: 4,500 to 11,000/µL

Differential count:
Neutrophils—segmented: 1,800 to 7,800/µL

Neutrophils—bands: 0 to 700/µL

Lymphocytes: 1,000 to 4,800/µL

Monocytes: 0 to 800/µL

Eosinophils: 0 to 450/µL

Basophils: 0 to 200/µL

Erythrocyte count: 3.9 to 5.5 × 106/µL

Hemoglobin: 14.0 to 17.5 g/dL

Hematocrit: 41% to 50%

Platelet count: 150 to 350 × 103/µL

Comments
 Normal in cluster headache

Levels may be depressed in anemia due to iron deficiency, chronic blood loss,
chronic hemolysis, or marrow failure

May be elevated in polycythemia due to myelodysplasia, smoking, chest disease,

abuse of erythropoietin, or physical training, especially at altitude

Temporal artery biopsy

 

Description

Biopsy of the superficial temporal artery; it is performed on patients when

temporal arteritis is suspected

Normal results

Normal temporal artery architecture

Comments

Temporal arteritis should be suspected in middle-aged or elderly patients with

temporal pain and a thickened, tender temporal artery. Not all features will be
present in all patients

Abnormal results include segmental inflammation of the superficial temporal

artery, which may be due to an inflammatory infiltrate

Corticosteroids may reduce inflammation such that it is no longer visible on the

biopsy

Biopsy can confirm the diagnosis of giant cell arteritis; however, it is invasive
and cannot definitively rule out temporal arteritis since the area of biopsy may
miss the zone of inflammation

Computed tomography scan

 

Description

Imaging modality in which a large series of radiographic images, taken around a

single axis of rotation, are subjected to digital processing; the result is a three-
dimensional image of the subject

Normal results

No evidence of subarachnoid or other types of hemorrhage, no evidence of mass

effect

Comments

CT scan can identify most common structural causes of headache; however, it is

 less sensitive than MRI for detection of infiltrating lesions

Abnormal results can include mass lesion, hydrocephalus, infarction,

hemorrhage, and cerebral edema

Lumbar puncture
 

Description

A needle is placed in the lumbar cistern to measure CSF pressure and to collect
CSF for analysis

Normal results

No signs of increased pressure or infection

Comments

Performed when there is clinical suspicion of hemorrhage, infection, or

increased intracranial pressure in the absence of demonstrated structural lesion
on imaging

Usually performed after brain imaging to ensure there is no mass lesion

Lumbar puncture identifies many cases of viral and bacterial meningitis and is
very sensitive for the detection of small amounts of subarachnoid blood
(xanthochromia)

Able to identify increased intracranial pressure, which may be seen with

pseudotumor cerebri, some infections, and venous thrombosis

Has a small potential for serious adverse effects, including herniation, if there is
a structural cause for increased intracranial pressure. Imaging should be
performed before the lumbar puncture in most circumstances

Small risk of bleeding, infection, paralysis, or death from lumbar puncture

Up to 10% of patients may develop a low-pressure headache after the procedure,

which is qualitatively different from their cluster headache. The low-pressure
headache usually responds to conservative therapy

Some medications, including selected nonsteroidal anti-inflammatory drugs

(NSAIDs), can cause a leukocytosis in the CSF, and some drugs can produce
increased intracranial pressure

Abnormal results:
Increased CSF pressure is seen in patients with pseudotumor cerebri, some
infections, and venous thrombosis

Inflammatory change: An increased leukocyte count is seen in most

 patients with infection, with the CSF profile suggesting bacterial, fungal, or
viral infection

Xanthochromia is a sign of subarachnoid hemorrhage

Magnetic resonance imaging

 

Description

Uses magnetic imaging and computer reconstruction to image brain tissues

Normal results

No evidence of mass or mass effect

Comments

MRI provides a sensitive evaluation for many serious causes of headache, such
as infiltrating brain masses

MRI is sensitive for intracranial structural lesions

Does not usually show meningitis and some causes of encephalitis that may
present with headaches

Abnormal results include mass lesion, hydrocephalus, infarction, hemorrhage,

and cerebral edema

Differential diagnosis
Migraine
 

Migraine headache falls into two major categories:

Common migraine: migraine without an aura

Classic migraine: migraine with an aura

Migraine aura consists of transient episodes of focal neurologic dysfunction

minutes to hours before onset of migraine headache

Aura symptoms typically include visual disturbance, unilateral paresthesias or

numbness, unilateral weakness, dysphasia, or other language disturbances

Dizziness is frequently a feature of migraine without aura

Prodromal symptoms begin 24 to 48 hours before an attack and can include:

hyperactivity, mild euphoria, lethargy, depression, craving for certain foods,
fluid retention, or frequent yawning

Headache phase of an attack is similar in migraine with or without aura: 4 to 72

hours of unilateral throbbing head pain of moderate to severe intensity that is
worsened by routine physical exertion and associated with nausea,
 photophobia, and phonophobia

Allodynia of the scalp and face is often a feature

Migraine may coexist with and is commonly triggered by other primary

headaches

Dental disease
 

Dental caries and abscess

Root canal infections

Parotid gland disease; inflammation, stone, tumor

Tooth impaction, particularly wisdom teeth

Pain is frequently felt in jaw or front of auricle

Temporomandibular joint dysfunction

 

The key features of temporomandibular joint dysfunction are as follows:

Chronic dull, aching, unilateral discomfort over the jaw, behind the eyes and
ears, and possibly down the neck and into the shoulders

Jaw with clicking sounds and difficulty opening mouth in the morning

Chewing may exacerbate symptoms; locking of the jaw is common

Molar prominences may be flat from chronic teeth grinding

Middle ear disease

 

Painful lesions of the middle ear, including otitis media , cholesteatoma , and
mastoiditis , may cause headache

Most commonly, ear pain refers to the throat and in front of the auricle

Abnormal appearance of the tympanic membrane

Giant cell arteritis

 

Giant cell arteritis , or temporal arteritis, is an inflammatory vasculitis that affects

medium and large arteries, and can cause blindness if it spreads to the
ophthalmic artery

All patients with suspected temporal arteritis should be started on corticosteroid

treatment immediately, before biopsy

Orbital or frontotemporal headache may begin as throbbing discomfort and

progress to dull and constant pain with superimposed jabbing sensations; some
 patients describe burning and others bouts of lancinating pain

Scalp tenderness, especially when the hair is combed, localized to the involved
vessel(s)

Inflamed artery may not always be tender or palpable; temporal artery is

commonly involved

Jaw/masticatory muscle claudication

Constitutional or musculoskeletal symptoms such as weight loss and anemia

Associated with polymyalgia rheumatica

ESR is elevated in 95% of cases

Onset usually after age 50

Substance-induced headache
 

Occurs with acute exposure to substances such as alcohol , carbon monoxide , and
indomethacin

Occurs with withdrawal from chronic use of substances such as alcohol,

barbiturates, caffeine, and cocaine

Over-the-counter medications may be involved

Trigeminal neuralgia
 

Trigeminal neuralgia ('tic douloureux') is one of the most severe pain syndromes.
This is a prototypical neuropathic pain syndrome

Paroxysms of lancinating, electric shock-like facial or cranial pain; these may

last only a few seconds but can be excruciating and recurrent

Jaw, gums, lips, or maxillary region may be involved

Trigger zone is located within the region of pain, and pain may be provoked by
stimulation of areas on the face quite discrete from the site of pain

Usually occurs in older patients

Sinusitis
 

The key features of sinusitis are as follows:

Headache is acute in onset; it is worse on awakening, gets better on rising, and

worsens again as the day progresses

Usually, headache occurs daily until it resolves

 Purulent nasal discharge, pain, and skin sensitivity are predominant over the
involved sinus

'Heavy-headed' feeling

Headache may be seasonal

Low-grade fever, toothache, and halitosis are common

Most self-diagnosed sinus headaches are actually migraine

Acute closed-angle glaucoma

 

The key features of acute glaucoma are as follows:

Severe pain, often behind the eye

Affected eye may feel rock hard

Halos seen around lights

Hazy cornea with a fixed, partially dilated pupil

Reduced vision

Red eye

Subarachnoid hemorrhage
 

The key features of subarachnoid hemorrhage are as follows:

Sudden onset of a severe, excruciating headache

May be accompanied by loss of consciousness and a neurologic deficit

The diagnosis is often made by means of an urgent CT scan, but a lumbar

puncture may be needed to rule out the diagnosis when clinical suspicion is
present

The patient needs to be referred to a specialized unit immediately

Intracranial tumor leading to increased intracranial pressure

 

Headache is a common presenting symptom of intracranial tumors (both benign

and malignant)

Usually dull and bifrontal pain, although pain tends to be worse on the side with
the tumor

Often qualitatively similar to tension-type headache: tends to be intermittent

and of moderate intensity
 Headache remains in the same location but is progressive; it increases in
duration and severity over several months in conjunction with subtle changes in
mental status or development of focal neurologic deficits

Accompanied by nausea in 50% of cases

Usually resistant to common analgesics

Factors that increase suspicion of an intracranial tumor include: papilledema,

new neurologic deficits, initial attack of prolonged headache after the age of 45,
previous malignancy, cognitive abnormality, or altered mental status

As intracranial pressure increases, lying down, straining at stool, coughing, or

bending over may exacerbate headache; a more generalized headache may
develop

Nocturnal awakening

Projectile vomiting can be a late complication

Pheochromocytoma
 

Pheochromocytoma is a rare disorder in which daily headache can be a symptom

Usually bioccipital pain that is exacerbated in the supine position

Often similar to cluster headache in that they recur daily, last less than 1 hour,
and have associated autonomic symptoms such as tachycardia, sweating, and
blood pressure changes. However, autonomic symptoms such as sweating
should be diffuse, not just on the side with the headache

Consultation
Dentistry consultation may be needed to ascertain that pain does not originate
from an impacted wisdom tooth

Consultation with an ear, nose, and throat specialist may be required for diagnosis
and treatment of sinusitis

Consultation with a neurosurgeon may be required to diagnose and treat certain

conditions such as pituitary tumors, cervical syringomyelia, Chiari malformation,
and idiopathic intracranial hypertension

Treatment
Summary approach
Acute treatments are available to shorten the cluster period or prevent anticipated
attacks

Prophylactic treatments are also available; these are important because of the
 limited usefulness of abortive agents and the intense nature of the pain

Avoid analgesic therapy for acute attacks, especially narcotic analgesics. Some
experts believe that narcotic analgesia changes the nature of the headache from
episodic to chronic cluster headache

Assess cardiovascular risk before instituting vasoactive medication

Abortive (symptomatic) treatments:

Oxygen (179851208851): sometimes used but is often not a convenient or practicable

therapy

Triptans (178027211_694): particularly sumatriptan ; zolmitriptan and naratriptan may also be

effective

Prednisone : often initiated while another long-term agent, such as verapamil or

lithium, is being employed

Dihydroergotamine : rapid onset of action, but frequency of headaches limits use for
cluster

Ergotamine : relatively slow onset of action when given orally often limits usefulness

Lidocaine : can be administered intranasally on the same side as the symptoms and
is occasionally helpful. Should only be performed by those trained in its
administration

Prophylactic treatments:

Prophylaxis with verapamil , lithium carbonate , or topiramate is sometimes helpful,

although combination therapy is often required with either two medications ( eg ,
verapamil and lithium carbonate, or verapamil and topiramate) or three
medications ( eg , verapamil, lithium, and ergotamine)

Second-line medications for prophylaxis include gabapentin , valproic acid , and β-

blockers (178212076_536)and are typically used as either monotherapy or in
combination as a long-term prophylactic agent

Amitriptyline , selective serotonin reuptake inhibitors (SSRIs) (178214281_686), and clonidine have
all been used with some success in the prevention of cluster headaches; however,
their role in therapy is yet to be defined

Civamide (1425059): One small study demonstrated limited efficacy for preventing the
development of cluster headaches. A pharmaceutical company-sponsored trial
(http://clinicaltrials.gov/ct2/show/NCT01341548)is currently underway

Trigeminal ganglion procedures (178027212_51): Electric currents or glycerol injection into

 the trigeminal cistern gives significant pain relief in patients with intractable
cluster headache but should be reserved for patients whose headaches are
refractory to all medical therapies

Acupuncture has been used as an alternative therapy for headaches of various

types and may have a role in the treatment of patients with cluster headache.
Clinical improvement has been reported by headache patients who underwent
acupuncture, but there is no quality data on the use of acupuncture for cluster
headaches

Melatonin has been suggested for preventing the development of cluster

headaches, but there is no quality evidence to support its efficacy

Psychologic therapies (178027215_851), such as relaxation, hypnosis, coping skills

training, biofeedback, and cognitive behavior therapy, may help patients manage
severe pain, but their effectiveness for cluster headache is unproven

Neuromodulation by targeted electrical stimulation or intrathecal medications is

currently under research for pain relief, including in cluster headache. Functional
imaging utilizing positron emission tomography (PET) scan has raised the
possibility that activation in the area of the posterior hypothalamus during attacks
of cluster headache may mitigate this form of headache
Deep brain stimulation of the posterior hypothalamus has shown efficacy in
one study in up to 60% of patients with medically-refractory cluster
headaches, but other studies failed to support this finding, and death has
been reported as a complication of this procedure

Stimulation of the sphenopalatine ganglion is well tolerated and safe, although

with localized loss of sensation in the distribution of the maxillary nerve as an
adverse effect

Medications
Oxygen
 

Indication

Abortive treatment for acute attacks

Dose information

Adults:

100% at 7 to 10 L for 10 to 15 minutes, inhaled through a tight-fitting face mask

Patient should be in a sitting position and breathing at normal respiratory rate

Major contraindications

Chronic obstructive pulmonary disease

 Naked flames

Comments

Can be of benefit in patients experiencing nausea

Evidence
A double-blind crossover study compared oxygen versus air inhalation at 6
L/min via nonrebreathing face masks for 15 minutes or less, for up to six
headaches. Oxygen-treated patients showed a significantly higher pain-relief
score. [1] Level of evidence: 2

In a randomized, controlled trial (RCT) crossover study to assess the

superiority of high-flow oxygen for the treatment of cluster headache to
placebo, 109 adult subjects treated four bouts of cluster headache with
inhaled high-flow oxygen or placebo, alternately. The treatment regimen with
oxygen included inhaled oxygen at 100%, 12 L/min, which was delivered by
face mask for 15 minutes at the start of an attack of cluster headache, or high-
flow air placebo, which was delivered alternately for four bouts of headache.
The aims of this study included rendering the study subjects pain free,
rendering them pain free at 30 minutes, pain reduction up to 30 minutes,
decreased use of rescue therapy, and reduction of functional disability. Only
57 subjects with episodic cluster headache and 19 subjects with chronic
cluster headache were available for the data analysis. Assessment of the data
demonstrated that the difference for the primary end point between oxygen
therapy (78%) and inhalation of air (20%) was statistically significant. The
treatment was not associated with any significant adverse events. [2] Level of
evidence: 1

This systematic review of nine studies compared normobaric and hyperbaric

oxygen therapy for the treatment of patients with migraine and cluster
headaches. Hyperbaric oxygen therapy includes utilization of 100% oxygen at
environmental pressures more than one atmosphere, while normobaric
oxygen treatment involves use of oxygen at one atmosphere pressure. Based
on the review of the results, a trend to better outcome in a single trial
evaluating hyperbaric oxygen therapy for cessation of an acute attack of
cluster headache (relative risk [RR] 11.38; 95% confidence interval [CI], 0.77-
167.85; P = .08) was detected, but this clinical trial had low power. On the
other hand, normobaric oxygen therapy was effective in ceasing cluster
headache compared to sham in one single small study (RR 7.88; 95% CI, 1.13-
54.66; P = .04); however, such effect was not superior to ergotamine
administration in another small trial (RR 1.17; 95% CI, 0.94-1.46; P = .16). The
reviewers reported that 66% of the study subjects responded to normobaric
oxygen therapy in these two clinical trials, and no serious adverse effects of
either hyperbaric oxygen therapy or normobaric oxygen therapy were
 reported. [3] Level of evidence: 1

References
Triptans
 

Indication

Triptans are used for abortive treatment of several types of headaches,

including cluster headaches

Dose information

Adults

Eletriptan :

20 to 40 mg orally at onset, may be repeated at 2-hour interval

Maximum: 80 mg/d

Naratriptan :

2.5 mg orally at onset, may be repeated at 4-hour interval

Maximum: 5 mg/d

Rizatriptan :

5 to 10 mg orally at onset, may be repeated at 2-hour interval

Maximum: 20 mg/d

Sumatriptan :

Either 25 to 100 mg orally at onset, may be repeated at 2-hour interval

Maximum: 200 mg/d

Or 6 mg intramuscularly at onset, may be repeated at 1-hour interval

Maximum: 12 mg/d

Zolmitriptan :

2.5 to 5 mg orally at onset, may be repeated at 2-hour interval

Maximum: 10 mg/d

Major contraindications

Acute myocardial infarction

Angina
 Arteriosclerosis

Basilar/hemiplegic migraine

Cardiac disease

Cerebrovascular disease (eletriptan, naratriptan, sumatriptan, zolmitriptan)

Coronary artery disease

Hepatic disease (naratriptan, sumatriptan)

Hypertension

Monoamine oxidase inhibitor (MAOI) therapy (rizatriptan, sumatriptan,

zolmitriptan)

Myocardial infarction (naratriptan, zolmitriptan)

Peripheral vascular disease (eletriptan, naratriptan, sumatriptan, zolmitriptan)

Renal disease (naratriptan)

Renal failure (naratriptan)

Stroke (eletriptan, naratriptan, sumatriptan, zolmitriptan)

Sumatriptan hypersensitivity (sumatriptan)

Vasospastic angina

Comments

Triptans can have a dramatic effect in curtailing a cluster headache and are the
mainstay in acute treatment if oxygen fails to produce an adequate response

Serious adverse effects, including myocardial infarction, stroke, and death, limit
their use

Drowsiness has implications for driving

Clinical trials of triptans did not include patients over 65 years of age, so clinical
information is not available for patients above this age group. In general, the
use of triptans in elderly patients is not recommended since these patients have
a higher incidence of declined hepatic activity, which may lead to a higher risk
of coronary artery disease and sudden surges in blood pressure

Significant elevations in blood pressure, including hypertensive crisis, have

been observed and were more significant in patients with renal impairment

Evidence
 A randomized, double-blind, placebo-controlled crossover trial of
subcutaneous sumatriptan found a significant increase in pain-free rates 10
to 15 minutes after administration of sumatriptan compared with placebo. [4]
Level of evidence: 2

A double-blind, placebo-controlled, randomized trial of intranasal

sumatriptan found a significant benefit in favor of sumatriptan over placebo
in response rates and pain-free rates at 30 minutes, with benefits also seen in
initial response, meaningful relief, and relief of associated symptoms. [5] Level
of evidence: 2

A systematic review of six trials with a total of 999 study subjects determined
the efficacy and tolerability of a single dose of triptan for the treatment of
acute attacks of cluster headache. In total, 231 patients were treated with
zolmitriptan 5 mg, 223 patients with zolmitriptan 10 mg, 131 patients with
sumatriptan 6 mg, 88 patients with sumatriptan 12 mg, and 326 patients were
on placebo. Zolmitriptan was given orally or intranasally, and sumatriptan
was administered either subcutaneously or intranasally. In general, the
triptans used in these trials demonstrated superiority over placebo for
headache relief and pain-free responses, with a number needed to treat
(NNT) of 2.4 for 15-minute pain relief with subcutaneous sumatriptan 6 mg
(75% with sumatriptan and 32% with placebo), and an NNT of 2.8 for 30-
minute pain relief with intranasal zolmitriptan 10 mg (62% with zolmitriptan
and 26% with placebo). Smaller numbers of patients who were treated with
triptans required rescue therapy compared to the placebo group; however,
adverse events were more frequent in the treatment group. The authors
concluded that both zolmitriptan and sumatriptan were effective in the
treatment of acute bouts of cluster headache, were more convenient than
oxygen treatment, and demonstrated better safety and tolerability profiles
than ergotamine. Administration of the medication via non-oral routes was
associated with faster therapeutic response and relief. [6] Level of evidence: 1

References
Prednisone
 

Indication

Prednisone is a corticosteroid used for acute and prophylactic treatment of cluster

headaches

Dose information

Adults

Acute treatment:

20 mg orally three times a day initially, then gradually reduced

 Treatment course: 14 days

Prophylactic treatment:

Either 60 to 80 mg orally once a day initially, then gradually reduced

Treatment course: 7 days

Or 40 mg orally once a day initially, then gradually reduced

Treatment course: 5 days tapered over 3 days

Major contraindications

Fungal infection

Comments

Prednisone is reported to be very effective in the prevention of refractory

cluster headache

Patients should be cautioned about adverse effects of corticosteroid therapy and

counseled that the potential benefits outweigh these risks in the short-term

Evidence
In a study of 19 patients with cluster headaches whose pain was not mitigated
by standard treatment, a double-blind control study with single crossover
showed sustained improvement on oral prednisone compared with placebo
in 17 cases. [7] Level of evidence: 3

References
Ergotamines
 

Indication

Abortive treatment

Dose information

Adults

Dihydroergotamine :

1 mg intramuscularly at onset, may be repeated at 1-hour interval

Maximum: 3 mg/d or 6 mg/wk

Ergotamine :

2 mg orally at onset, may be repeated at 1-hour interval, then not repeated for 4
days
 Maximum: 6 mg/d or 10 mg/wk

Major contraindications

Angina (dihydroergotamine)

Basilar/hemiplegic migraine (dihydroergotamine)

Breastfeeding (dihydroergotamine)

Coronary artery disease (ergotamine)

Eclampsia

Ergot alkaloid hypersensitivity

Hepatic disease (ergotamine)

Hypertension

Labor

Malnutrition (ergotamine)

Myocardial infarction (dihydroergotamine)

Obstetric delivery

Peripheral vascular disease

Preeclampsia

Pregnancy

Renal failure (ergotamine)

Renal impairment (ergotamine)

Sepsis

Surgery (dihydroergotamine)

Comments

Ergotamine preparations are usually combined with caffeine

All ergotamines have a poor adverse effect profile, extensive serious

interactions, and numerous contraindications. Risk of ergotism limits their use
and patient acceptability

Evidence
A small double-blind, placebo-controlled trial showed a significant effect on
 the intensity of single pain attacks with dihydroergotamine nasal spray. [8]
Level of evidence: 2

References
Lidocaine
 

Indication

Lidocaine is a local anesthetic used for abortive treatment of cluster headaches

This is an off-label indication

Dose information

Adults, 4% topical solution:

1 mL intranasally twice per headache, may be repeated at 15-minute interval

Maximum: 8 mL/d

Major contraindications

Amide local anesthetic hypersensitivity

Sepsis

Comments

Lidocaine will be absorbed very rapidly if there is sepsis or extremely

traumatized mucosa in the area of application; hypersensitivity reactions,
including anaphylaxis, can occur

Can be very effective in treating cluster headache

Viscous solution is for topical use only and must not be used for injection

Evidence
Nitroglycerin-induced pain in cluster headache showed a prompt response
with cessation of pain after local application of cocaine hydrochloride or
lidocaine in the area corresponding to the sphenopalatine fossa, under
anterior rhinoscopy. [9] Level of evidence: 2

References
Verapamil
 

Indication

Verapamil is a calcium-channel blocker used for prophylactic treatment of cluster

headaches
 This is an off-label indication

Dose information

Adults:

Immediate-release: 80 to 160 mg orally three times a day

Sustained-release: 120 to 480 mg/d orally

Major contraindications

Atrioventricular block

Cardiogenic shock

Heart failure

Hypotension

Lown-Ganong-Levine syndrome

Sick sinus syndrome

Ventricular dysfunction

Ventricular tachycardia

Wolff-Parkinson-White syndrome

Comments

Some experts consider verapamil first-line therapy for cluster headache

prophylaxis

Can cause a fall in blood pressure and should be used with caution in patients
with existing cardiac complications

Patients who are treated with doses more than 120 mg need electrocardiogram
monitoring because of the risk of dysrhythmias

Evidence
A small RCT compared the efficacy of verapamil versus placebo in the
prophylaxis of episodic cluster headache. There was a significant reduction in
the frequency of attacks and in the consumption of abortive agents in the
verapamil-treated group, suggesting that verapamil is effective in episodic
cluster headache prophylaxis. [10] Level of evidence: 2

In a double-dummy, double-blind, crossover comparison of verapamil with

lithium carbonate in preventing chronic cluster headache attacks, both
 agents were found to be effective in preventing chronic cluster headache
attacks, but verapamil caused fewer adverse effects and had a shorter latency
period. [11] Level of evidence: 2

References
Lithium
 

Indication

Lithium carbonate is an antimania agent used for prophylactic treatment of patients

with chronic cluster headaches

This is an off-label indication

Dose information

Adults:

300 mg orally four times a day

Maximum: 1,200 mg/d

Comments

The narrow therapeutic index increases the risk of toxicity associated with the
use of lithium, especially at the higher doses given for cluster headache
prophylaxis

The adverse effect profile and toxicity problems limit its use and patient
acceptability

Evidence
In a double-dummy, double-blind, crossover comparison of verapamil with
lithium carbonate in preventing chronic cluster headache attacks, both
agents were found to be effective in preventing chronic cluster headache
attacks, but verapamil caused fewer adverse effects and had a shorter latency
period. [11] Level of evidence: 2

References
Topiramate
 

Indication

Topiramate is an anticonvulsant used for prophylactic treatment of cluster

headaches

This is an off-label indication

Dose information
Adults:

Initially 25 to 50 mg orally once or twice a day

Maximum: 200 mg/d

Comments

Drowsiness and changes to seizure threshold limit its acceptability to patients

Gabapentin
 

Indication

Gabapentin is an anticonvulsant used for prophylactic treatment of cluster

headaches

This is an off-label indication

Dose information

Adults:

Initially 300 mg orally twice a day, increased up to 2,400 mg/d in equally divided
doses

Maximum: 3,600 mg/d

Comments

There is evidence to support its use in neuropathic pain; however, this has not
been extended to cluster headaches

Drowsiness and changes to seizure threshold limit its acceptability to patients

Valproic acid
 

Indication

Valproic acid is an anticonvulsant used for prophylactic treatment of cluster

headaches

This is an off-label indication

Dose information

Adults, extended-release:

Initially 500 mg/d orally, increased until therapeutic response is achieved

Major contraindications

Hepatic disease
 Mitochondrial disease

Comments

Valproate can cause serious or fatal adverse effects

Beta-blockers
 

Indication

Used for prophylactic treatment of cluster headaches

This is an off-label indication

Dose information

Adults

Atenolol :

50 to 100 mg orally once a day

Maximum: 100 mg/d

Nadolol :

40 mg orally once a day

Propranolol :

Initially 80 mg/d orally, can increase to 160 to 240 mg/d

Maximum: 240 mg/d

Major contraindications

Asthma (nadolol, propranolol)

Atrioventricular block

Bradycardia

Cardiogenic shock

Heart failure (atenolol, nadolol)

Sick sinus syndrome (propranolol)

Comments

β-blockers can precipitate or exacerbate cardiac failure; however, they are

effective in the prevention of cluster headache
 Amitriptyline

 
Indication

Amitriptyline is a tricyclic antidepressant used for prophylactic treatment of cluster

headaches

This is an off-label indication

Dose information

Adults:

10 to 25 mg orally at night

Maximum: 150 to 200 mg/d

Major contraindications

Acute myocardial infarction

Carbamazepine hypersensitivity

MAOI therapy

Comments

A poor adverse effect profile, including anticholinergic effects, limits its

acceptability to patients

Reports of increased risk of suicidality with tricyclic antidepressant use

Selective serotonin reuptake inhibitors

 

Indication

Used for prophylactic treatment of cluster headaches

This is an off-label indication

Dose information

Adults

Citalopram :

20 mg orally once a day

Maximum: 60 mg/d

Fluoxetine :

20 mg orally once a day

 Maximum: 80 mg/d

Paroxetine :

20 mg orally once a day

Maximum: 50 mg/d

Major contraindications

Citalopram hypersensitivity (citalopram)

MAOI therapy (citalopram, paroxetine)

Pregnancy (paroxetine)

Comments

SSRIs are effective in the prevention of cluster headache

Fewer anticholinergic effects than tricyclic antidepressants, and also safer in

overdose

Reports of increased risk of suicidality associated with the use of these

medications

Clonidine
 

Indication

Clonidine is an α-agonist used for prophylactic treatment of cluster headaches

This is an off-label indication

Dose information

Adults:

Initially 50 μg orally twice a day

Maximum: 150 μg/d

Comments

Clonidine is effective in the prevention of cluster headaches; however, it can

cause a dramatic drop in blood pressure, exacerbating or precipitating
cardiovascular problems

Civamide
 

Indication

Used for prophylactic treatment of cluster headaches

 Dose information

25 μg/d

Major contraindications

Known history of hypersensitivity to utilization of civamide or capsaicin

Comments

Civamide is a synthetic isomer of capsaicin and works as a vanilloid receptor

agonist and a neuronal calcium-channel blocker, which suppresses the neuronal
release of excitatory neurotransmitters

Limited evidence indicates that intranasal civamide 100 μg of 0.025% (25 μg) is
effective in improving headache responses in patients with cluster headache

Evidence
A multi-center, double-blind, randomized study assessed the safety and
efficacy of intranasal civamide solution for prevention treatment in patients
with an episodic cluster headache period. A group of 28 patients with cluster
headache were treated with either 100 μL (25 μg) of 0.025% civamide or its
vehicle into each nostril daily for 1 week. The study subjects were followed-
up for 20 days after the initial treatment. Patients who received civamide
showed a greater decline in the number of headaches compared to the
placebo-treated group during days 1 through 7 (−55.5% vs −25.9%; P = .03).
There was only a trend toward significant improvement during days 8
through 14 (−66.9% vs −32.3%; P = .07) and days 15 through 20 (−70.6% vs
−34.9%; P = .07) compared to the vehicle group. The number of headaches per
week during the posttreatment period in the civamide-treated group
decreased more, with trends toward significance during posttreatment days 8
through 14 (−8.6 vs −3.6; P = .09) and days 15 through 20 (−8.9 vs −3.6; P = .07).
The most frequent adverse effects included nasal burning, lacrimation,
pharyngitis, and rhinorrhea. [12] Level of evidence: 3

References
Non-drug treatments
Trigeminal ganglion procedures
 

Description

Radiofrequency trigeminal gangliolysis and percutaneous stereotactic

rhizotomy are outpatient procedures where the surgeon passes an electrode
introducer into the trigeminal nerve. A heating current is then usually passed
through the electrode, destroying selected nerve fibers

Some experts inject glycerol rather than pass a current

Indications

Used to treat carefully selected refractory patients with strictly unilateral

attacks

Reserved for patients whose headaches are completely refractory to all medical
therapies

Blockade of second and third divisions of trigeminal nerve is useful in the

management of pain syndromes in selected patients

Complications

Potential for ipsilateral corneal injury secondary to corneal anesthesia that

results from the procedure

Hematoma formation secondary to maxillary nerve block

Temporary blindness secondary to the spread of the local anesthetic to the optic
nerve

Infection in infratemporal fossa if the needle is advanced past the pterygoid

plate

Brainstem anesthesia secondary to the spread of local anesthetic into the

subarachnoid space

Comments

Glycerol injection into trigeminal cistern gives significant pain relief in patients
with intractable cluster headache

Relaxation and related psychotherapies

 

Description

Psychologic therapies such as relaxation, hypnosis, coping skills training,

biofeedback, and cognitive behavior therapy

Indications

These treatments may help people manage severe pain and cope better with
disabilities associated with chronic or recurrent pain

Complications

No risks have been described

Comments

Cognitive behavior therapy is the treatment that helps people test and revise
 their thoughts and actions

Persons properly trained and certified in the techniques being offered should be
sought for these therapies

Special circumstances
Comorbidities
Special populations:

Pregnant patients with cluster headache should be treated with oxygen

In many patients, pregnancy may significantly improve cluster headache

Consultation
Patients with intractable bouts of cluster headache who have failed medical treatment
should be referred to a neurosurgeon for surgical treatment of pain.

Follow-up
Monitoring:

Provide supportive relationship and follow-up

Follow-up is needed to determine response to treatment and the natural history of

the condition in the individual patient

Patients should be reviewed regularly (monthly or quarterly) to ensure that the

headache is well controlled, and that they are not overdosing to control their pain

Prognosis:

Cluster headache is a self-limiting condition, and the symptoms may eventually

subside spontaneously, usually after a number of years, with no long-lasting or
serious effects

Clusters are interspersed by epochs with little or no headache

Most patients with cluster headache respond to abortive and preventive medication

Complications:

Rarely, patients move from an acute to chronic pattern of cluster headaches

Self-injury during attack

Adverse effects of medication, including unmasking of coronary heart disease

Potential for opiate abuse

Secondary prevention:

Prophylactic medicines can be effective in preventing attacks

Improve sleep cycle; disruption common due to anticipation and occurrence of

nocturnal attacks

Avoid narcotic analgesics, especially oral preparations, which may expedite

transformation of episodic cluster to chronic cluster

During cluster periods, avoid alcohol, bright lights and glare, excessive emotion, and
stress as these may precipitate attacks

Avoid tobacco as it may make the patient more refractory to therapy

Avoid high altitudes

Vigorous physical activity at first symptom may abort an attack

Encourage patient to focus on validity, natural history, and pathology of the condition

Assist the patient with learning self-treatment methods

Patient education
Recurrence of the headaches is possible; patients should contact their physician and
start treatment if this happens

Avoiding trigger factors will decrease cluster headaches

This is a self-limiting condition, and the symptoms will eventually subside

spontaneously with no long-lasting or serious effects

Online information for patients

American Headache Society: Cluster headache
(http://www.achenet.org/resources/cluster_headache/)

Mayo Clinic: Cluster headache (http://www.mayoclinic.com/health/cluster-headache/DS00487)

Cleveland Clinic: Cluster headaches

(http://my.clevelandclinic.org/disorders/cluster_headaches/hic_cluster_headaches.aspx)

Resources
Summary of evidence
Evidence
Oxygen:

A double-blind crossover study compared oxygen versus air inhalation at 6

 L/min via nonrebreathing face masks for 15 minutes or less, for up to six
headaches. Oxygen-treated patients showed a significantly higher pain-relief
score. [1] Level of evidence: 2

In an RCT crossover study to assess the superiority of high-flow oxygen for the
treatment of cluster headache to placebo, 109 adult subjects treated four bouts
of cluster headache with inhaled high-flow oxygen or placebo, alternately. The
treatment regimen with oxygen included inhaled oxygen at 100%, 12 L/min,
which was delivered by face mask for 15 minutes at the start of an attack of
cluster headache, or high-flow air placebo, which was delivered alternately for
four bouts of headache. The aims of this study included rendering the study
subjects pain free, rendering them pain free at 30 minutes, pain reduction up to
30 minutes, decreased use of rescue therapy, and reduction of functional
disability. Only 57 subjects with episodic cluster headache and 19 subjects with
chronic cluster headache were available for the data analysis. Assessment of the
data demonstrated that the difference for the primary end point between
oxygen therapy (78%) and inhalation of air (20%) was statistically significant.
The treatment was not associated with any significant adverse events. [2] Level of
evidence: 1

This systematic review of nine studies compared normobaric and hyperbaric

oxygen therapy for the treatment of patients with migraine and cluster
headaches. Hyperbaric oxygen therapy includes utilization of 100% oxygen at
environmental pressures more than one atmosphere, while normobaric oxygen
treatment involves use of oxygen at one atmosphere pressure. Based on the
review of the results, a trend to better outcome in a single trial evaluating
hyperbaric oxygen therapy for cessation of an acute attack of cluster headache
(RR 11.38; 95% CI, 0.77-167.85; P = .08) was detected, but this clinical trial had
low power. On the other hand, normobaric oxygen therapy was effective in
ceasing cluster headache compared to sham in one single small study (RR 7.88;
95% CI, 1.13-54.66; P = .04); however, such effect was not superior to ergotamine
administration in another small trial (RR 1.17; 95% CI, 0.94-1.46; P = .16). The
reviewers reported that 66% of the study subjects responded to normobaric
oxygen therapy in these two clinical trials, and no serious adverse effects of
either hyperbaric oxygen therapy or normobaric oxygen therapy were reported.
[3] Level of evidence: 1

Triptans:

A randomized, double-blind, placebo-controlled crossover trial of subcutaneous

sumatriptan found a significant increase in pain-free rates 10 to 15 minutes
after administration of sumatriptan compared with placebo. [4] Level of evidence:
2

A double-blind, placebo-controlled, randomized trial of intranasal sumatriptan

found a significant benefit in favor of sumatriptan over placebo in response
 rates and pain-free rates at 30 minutes, with benefits also seen in initial
response, meaningful relief, and relief of associated symptoms. [5] Level of
evidence: 2

A systematic review of six trials with a total of 999 study subjects determined
the efficacy and tolerability of a single dose of triptan for the treatment of acute
attacks of cluster headache. In total, 231 patients were treated with zolmitriptan
5 mg, 223 patients with zolmitriptan 10 mg, 131 patients with sumatriptan 6 mg,
88 patients with sumatriptan 12 mg, and 326 patients were on placebo.
Zolmitriptan was given orally or intranasally, and sumatriptan was
administered either subcutaneously or intranasally. In general, the triptans
used in these trials demonstrated superiority over placebo for headache relief
and pain-free responses, with an NNT of 2.4 for 15-minute pain relief with
subcutaneous sumatriptan 6 mg (75% with sumatriptan and 32% with placebo),
and an NNT of 2.8 for 30-minute pain relief with intranasal zolmitriptan 10 mg
(62% with zolmitriptan and 26% with placebo). Smaller numbers of patients
who were treated with triptans required rescue therapy compared to the
placebo group; however, adverse events were more frequent in the treatment
group. The authors concluded that both zolmitriptan and sumatriptan were
effective in the treatment of acute bouts of cluster headache, were more
convenient than oxygen treatment, and demonstrated better safety and
tolerability profiles than ergotamine. Administration of the medication via non-
oral routes was associated with faster therapeutic response and relief. [6] Level of
evidence: 1

Prednisone:

In a study of 19 patients with cluster headaches whose pain was not mitigated
by standard treatment, a double-blind control study with single crossover
showed sustained improvement on oral prednisone compared with placebo in
17 cases. [7] Level of evidence: 3

Dihydroergotamine:

A small double-blind, placebo-controlled trial showed a significant effect on the

intensity of single pain attacks with dihydroergotamine nasal spray. [8] Level of
evidence: 2

Lidocaine:

Nitroglycerin-induced pain in cluster headache showed a prompt response with

cessation of pain after local application of cocaine hydrochloride or lidocaine in
the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy.
[9] Level of evidence: 2

Verapamil:
 A small RCT compared the efficacy of verapamil versus placebo in the
prophylaxis of episodic cluster headache. There was a significant reduction in
the frequency of attacks and in the consumption of abortive agents in the
verapamil-treated group, suggesting that verapamil is effective in episodic
cluster headache prophylaxis. [10] Level of evidence: 2

In a double-dummy, double-blind, crossover comparison of verapamil with

lithium carbonate in preventing chronic cluster headache attacks, both agents
were found to be effective in preventing chronic cluster headache attacks, but
verapamil caused fewer adverse effects and had a shorter latency period. [11]
Level of evidence: 2

Lithium:

In a double-dummy, double-blind, crossover comparison of verapamil with

lithium carbonate in preventing chronic cluster headache attacks, both agents
were found to be effective in preventing chronic cluster headache attacks, but
verapamil caused fewer adverse effects and had a shorter latency period. [11]
Level of evidence: 2

Civamide:

A multi-center, double-blind, randomized study assessed the safety and efficacy

of intranasal civamide solution for prevention treatment in patients with an
episodic cluster headache period. A group of 28 patients with cluster headache
were treated with either 100 μL (25 μg) of 0.025% civamide or its vehicle into
each nostril daily for 1 week. The study subjects were followed-up for 20 days
after the initial treatment. Patients who received civamide showed a greater
decline in the number of headaches compared to the placebo-treated group
during days 1 through 7 (−55.5% vs −25.9%; P = .03). There was only a trend
toward significant improvement during days 8 through 14 (−66.9% vs −32.3%; P
= .07) and days 15 through 20 (−70.6% vs −34.9%; P = .07) compared to the
vehicle group. The number of headaches per week during the posttreatment
period in the civamide-treated group decreased more, with trends toward
significance during posttreatment days 8 through 14 (−8.6 vs −3.6; P = .09) and
days 15 through 20 (−8.9 vs −3.6; P = .07). The most frequent adverse effects
included nasal burning, lacrimation, pharyngitis, and rhinorrhea. [12] Level of
evidence: 3

References
References
Evidence references
1. Fogan L. Treatment of cluster headache. A double-blind comparison of oxygen v
air inhalation. Arch Neurol. 1985;42:362-3
View In Article (refInSitucid_04531)
2. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster
headache: a randomized trial. JAMA. 2009;302:2451-7
View In Article (refInSitu53551) | CrossRef (http://dx.doi.org/10.1001%2Fjama.2009.1855)

3. Bennett MH, French C, Schnabel A, Wasiak J, Kranke P. Normobaric and

hyperbaric oxygen therapy for migraine and cluster headache. Cochrane Database
Syst Rev. 2008:CD005219
View In Article (refInSitu53552) | CrossRef (http://dx.doi.org/10.1002%2F14651858.CD005219.pub2)

4. Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache

with sumatriptan. The Sumatriptan Cluster Headache Study Group. N Engl J Med.
1991;325:322-6
View In Article (refInSitucid_04537)

5. van Vliet JA, Bahra A, Martin V, et al. Intranasal sumatriptan in cluster headache:
randomized placebo-controlled double-blind study. Neurology. 2003;60:630-3
View In Article (refInSitucid_04538)

6. Law S, Derry S, Moore RA. Triptans for acute cluster headache. Cochrane Database
Syst Rev. 2010:CD008042
View In Article (refInSitu53553) | CrossRef (http://dx.doi.org/10.1002%2F14651858.CD008042.pub2)

7. Jammes JL. The treatment of cluster headaches with prednisone. Dis Nerv Syst.
1975;36:375-6
View In Article (refInSitucid_04532)

8. Andersson PG, Jespersen LT. Dihydroergotamine nasal spray in the treatment of

attacks of cluster headache. A double-blind trial versus placebo. Cephalalgia.
1986;6:51-4
View In Article (refInSitucid_04528)

9. Costa A, Pucci E, Antonaci F, et al. The effect of intranasal cocaine and lidocaine
on nitroglycerin-induced attacks in cluster headache. Cephalalgia. 2000;20:85-91
View In Article (refInSitucid_04530) | CrossRef (http://dx.doi.org/10.1046%2Fj.1468-
2982.2000.00026.x)

10. Leone M, D'Amico D, Frediani F, et al. Verapamil in the prophylaxis of episodic

cluster headache: a double-blind study versus placebo. Neurology. 2000;54:1382-5
View In Article (refInSitucid_04533)

11. Bussone G, Leone M, Peccarisi C, et al. Double blind comparison of lithium and
verapamil in cluster headache prophylaxis. Headache. 1990;30:411-7
View In Article (refInSitucid_04529) | CrossRef (http://dx.doi.org/10.1111%2Fj.1526-
4610.1990.hed3007411.x)

12. Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, Bernstein JE. Intranasal
civamide for the treatment of episodic cluster headaches. Arch Neurol. 2002;59:990-
 4
View In Article (refInSitu53554)

Guidelines
The American Academy of Neurology (http://www.aan.com/)has produced the following:

Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacologic treatment of
cluster headache (http://www.neurology.org/content/75/5/463.full.pdf). Neurology.
2010;75:463-73 (registration required)

The National Clinical Guideline Centre (http://www.ncgc.ac.uk/), UK, has produced the following:

Underwood M, Bhola R, Davies B, et al. Headaches: diagnosis and management of

headaches in young people and adults. Clinical guideline 150: methods, evidence and
recommendations (http://www.nice.org.uk/nicemedia/live/13901/60854/60854.pdf).
Commissioned by the National Institute for Health and Clinical Excellence.
London: The Royal College of Physicians; 2012

The American College of Emergency Physicians (http://www.acep.org/)has produced the

following:

Edlow JA, Panagos PD, Godwin SA, Thomas TL, Decker WW. Clinical policy: critical
issues in the evaluation and management of adult patients presenting to the emergency
department with acute headache (http://www.annemergmed.com/article/S0196-
0644%2808%2901463-7/fulltext). Ann Emerg Med. 2008;52:407-36

The European Federation of Neurological Societies (http://www.efns.org/)has produced the

following:

May A, Leone M, Afra J, et al, and the EFNS Task Force. EFNS guidelines on the
treatment of cluster headache and other trigeminal-autonomic cephalalgias
(http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2006.01566.x/full). Eur J Neurol.
2006;13:1066-77 (registration required)

Further reading
Walker RA, Wadman MC. Headache in the elderly. Clin Geriatr Med.
2007;23:291-305

McConaghy JR. Headache in primary care. Prim Care. 2007;34:83-97

Russell MB. Epidemiology and genetics of cluster headache. Lancet Neurol.

2004;3:279-83

Gladstein J. Headache. Med Clin North Am. 2006;90:275-90

Silberstein SD. Headaches in pregnancy. Neurol Clin. 2004;22:727-56

Krusz JC. Tension-type headaches: what they are and how to treat them. Prim
Care. 2004;31:293-311

Hutchinson S. Chronic daily headache. Prim Care. 2004;31:353-67

Lipton RB, Bigal ME, Steiner TJ, Silberstein SD, Olesen J. Classification of primary
headaches. Neurology. 2004;63:427-35

Friedman BW, Hochberg ML, Esses D, et al. Applying the International

Classification of Headache Disorders to the emergency department: an
assessment of reproducibility and the frequency with which a unique diagnosis
can be assigned to every acute headache presentation. Ann Emerg Med.
2007;49:409-19

Beck E, Sieber WJ, Trejo R. Management of cluster headache. Am Fam Physician.

2005;71:717-24

Clinch CR. Evaluation of acute headaches in adults. Am Fam Physician.

2001;63:685-92

Lewis DW. Headaches in children and adolescents. Am Fam Physician.

2002;65:625-32

Evers S, Fischera M, May A, Berger K. Prevalence of cluster headache in

Germany: results of the epidemiological DMKG study. J Neurol Neurosurg
Psychiatry. 2007;78:1289-90

Weintraub JR. Cluster headaches and sleep disorders. Curr Pain Headache Rep.
2003;7:150-6

Nesbitt AD, Goadsby PJ. Cluster headache. BMJ. 2012;344:e2407

Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster
headache: a randomized trial. JAMA. 2009;302:2451-7

May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation

in cluster headache attacks. Lancet. 1998;352:275-8

Brittain JS, Green AL, Jenkinson N, et al. Local field potentials reveal a
distinctive neural signature of cluster headache in the hypothalamus.
Cephalalgia. 2009;29:1165-73

Leone M. Deep brain stimulation in headache. Lancet Neurol. 2006;5:873-7

Fontaine D, Lazorthes Y, Mertens P, et al. Safety and efficacy of deep brain

stimulation in refractory cluster headache: a randomized placebo-controlled
double-blind trial followed by a 1-year open extension. J Headache Pain.
2010;11:23-31
 Schoenen J, Di Clemente L, Vandenheede M, et al. Hypothalamic stimulation in
chronic cluster headache: a pilot study of efficacy and mode of action. Brain.
2005;128:940-7

Schoenen J, Jensen RH, Lantéri-Minet M, et al. Stimulation of the sphenopalatine

ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized,
sham-controlled study. Cephalalgia. 2013;33:816-30

Goadsby PJ. Sphenopalatine (pterygopalatine) ganglion stimulation and cluster

headache: new hope for ye who enter here. Cephalalgia. 2013;33:813-5

Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus

placebo in the prophylaxis of cluster headache: a double-blind pilot study with
parallel groups. Cephalalgia. 1996;16:494-6

Codes
ICD-9 code
339.00 Cluster headache syndrome, unspecified

339.01 Episodic cluster headache

339.02 Chronic cluster headache

ICD-10 code
G44.00 Cluster headache syndrome, unspecified

G44.01 Episodic cluster headache

G44.02 Chronic cluster headache

FAQ
What are the headaches classified under trigeminal autonomic cephalgias?
Cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform
headache attacks with conjunctival injection and tearing (SUNCT), and hemicrania
continua. These headaches are primary headache syndromes, which are
recognized by the presence of headache along with autonomic features

What is the relationship between the cluster headache and the patient's stage
of sleep? Cluster headaches possess a preference for the first REM sleep phase;
therefore, the patient wakes up with a severe headache within 60 to 90 minutes of
falling asleep

What are the autonomic manifestations of cluster headache? These

manifestations include lacrimation, rhinorrhea, conjunctival injection, ptosis,
miosis (Horner syndrome), and facial or periorbital swelling

What are the common triggers associated with cluster headache? Chronic
 tobacco use, obstructive sleep apnea, and alcohol overuse

What treatments are available to patients who do not respond to medical

treatment? Surgical treatment should be considered for patients who have
exhausted medical treatment with oxygen 100%, sumatriptan, zolmitriptan, and
intranasal lidocaine. Surgical procedures, which usually target the sensory portion
of the trigeminal nerve, include radiofrequency thermocoagulation, trigeminal
root section, and alcohol injection into the supraorbital and infraorbital nerves.
Recently, hypothalamic stimulation has been suggested. The major complications
of these procedures include sensory loss beyond the area affected, keratitis, and
corneal anesthesia

Current contributors
Alireza Minagar, MD, FAAN, FANA, Professor, Department of Neurology, Louisiana State
University Health Sciences Center, Shreveport, Louisiana

Copyright © 2016 Elsevier, Inc. All rights reserved.