Cluster Headache—Acute and Prophylactic Therapy

Avi Ashkenazi, MD; Todd Schwedt, MD


Headache. 2011;51(2):272-286. 

In This Article

Abstract and Introduction


Cluster headache (CH) pain is the most severe of the primary headache syndromes. It is characterized by periodic attacks of strictly unilateral pain associated with ipsilateral cranial autonomic symptoms. The majority of patients have episodic CH, with cluster periods that typically occur in a circannual rhythm, while 10% suffer from the chronic form, with no significant remissions between cluster periods. Sumatriptan injection or oxygen inhalation is the first-line therapy for acute CH attacks, with the majority of patients responding to either treatment. The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen. Transitional prophylaxis, most commonly using corticosteroids, helps to control the attacks at the beginning of a cluster period. Peripheral neural blockade is effective for short-term pain control. Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation. With the emergence of these novel treatments, the role of ablative surgery in CH has declined.


Cluster headache (CH) pain is considered the most severe of the primary headache syndromes and is arguably one of the most severe pain syndromes that afflict humans.[1] The disorder is characterized by attacks of severe, strictly unilateral pain, typically in the retro-orbital and fronto-temporal areas, associated with symptoms and signs of cranial autonomic dysfunction (tearing, conjunctival injection, rhinorrhea/nasal congestion, and Horner's syndrome) ipsilateral to the pain. Patients typically pace restlessly during an acute attack. The hallmark of CH is the circadian periodicity of the attacks. Also, in episodic CH (ECH), the cluster periods often occur at predictable times of the year (circannual periodicity). Recent imaging studies confirm activation of the hypothalamus during CH attacks.[2] These findings may explain the characteristic periodicity of CH. Activation of the trigeminovascular system has also been shown during acute attacks.

The management of CH includes: (1) patient education about the nature of the disorder; (2) advice on lifestyle changes (eg, avoiding alcohol during an active cluster period); (3) prompt treatment of the acute attack; and (4) prophylactic treatment. Most patients can be managed with medical therapy. Rarely, surgical treatment is indicated. Recently, neurostimulation has emerged as a therapeutic option for select patients.

We performed a PubMed search of the English literature to find studies on the acute and prophylactic treatment of CH. Search terms were CH and each of the following: acute treatment, prophylactic (or preventive) treatment, triptans, oxygen, ergotamine, dihydroergotamine, lidocaine, somatostatin, octreotide, verapamil, lithium, topiramate, valproic acid, methysergide, gabapentin, baclofen, melatonin, botulinum toxin, corticosteroids, neurostimulation, occipital nerve block/stimulation, sphenopalatine ganglion block/stimulation, hypothalamic stimulation, radiofrequency, trigeminal rhizotomy, gamma knife surgery, microvascular decompression. We did not limit our search to a specific time period. We focused on clinical efficacy and tolerability of the various drugs and procedures based on data from human studies. We included the best available studies for each discussed drug or procedure. These ranged from randomized controlled trials for some treatments, to small case series for others.


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