Evidence-based treatments for cluster headache

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Abstract

Cluster headache (CH), one of the most painful syndromes known to man, is managed with acute and preventive medications. The brief duration and severity of the attacks command the use of rapid-acting pain relievers. Inhalation of oxygen and subcutaneous sumatriptan are the two most effective acute therapeutic options for sufferers of CH. Several preventive medications are available, the most effective of which is verapamil. However, most of these agents are not backed by strong clinical evidence. In some patients, these options can be ineffective, especially in those who develop chronic CH. Surgical procedures for the chronic refractory form of the disorder should then be contemplated, the most promising of which is hypothalamic deep brain stimulation. We hereby review the pathogenesis of CH and the evidence behind the treatment options for this debilitating condition.

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Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies.

Peter J Goadsby, Lars Edvinsson (1994)

Cluster headache is a rare very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. In this study patients with episodic cluster headache fulfilling the criteria of the International Headache Society were examined during an acute spontaneous attack of headache to determine the local cranial release of neuropeptides. Blood was sampled from the external jugular vein ipsilateral to the pain before and after treatment of the attack. Samples were assayed for calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P and neuropeptide Y. Attacks were treated with either oxygen inhalation, sumatriptan or an opiate. Thirteen patients were studied of whom 10 were male and three female. All had well-established typical attacks of cluster headache when blood was sampled. During the attacks external jugular vein blood levels of CGRP and VIP were raised while there was no change in neuropeptide Y or substance P. Calcitonin gene-related peptide levels rose to 110 +/- 7 pmol/l (normal: < 40) while VIP levels rose to 20 +/- 3 pmol/l (normal: < 7). Treatment with both oxygen and subcutaneous sumatriptan reduced the CGRP level to normal, while opiate administration did not alter the peptide levels. These data demonstrate for the first time in vivo human evidence for activation of the trigeminovascular system and the cranial parasympathetic nervous system in an acute attack of cluster headache. Furthermore, it is shown that both oxygen and sumatriptan abort the attacks and terminate activity in the trigeminovascular system.

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EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias.

P Sándor, Massimo Leone, M Linde … (2006)

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.

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High-flow oxygen for treatment of cluster headache: a randomized trial.

Anna Cohen, Brian Burns, Peter J Goadsby (2009)

Cluster headache is an excruciatingly painful primary headache syndrome, with attacks of unilateral pain and cranial autonomic symptoms. The current licensed treatment for acute attacks is subcutaneous sumatriptan. To ascertain whether high-flow inhaled oxygen was superior to placebo in the acute treatment of cluster headache. A double-blind, randomized, placebo-controlled crossover trial of 109 adults (aged 18-70 years) with cluster headache as defined by the International Headache Society. Patients treated 4 headache episodes with high-flow inhaled oxygen or placebo, alternately. Patients were randomized to the order in which they received the active treatment or placebo. Patients were recruited and followed up between 2002 and 2007 at the National Hospital for Neurology and Neurosurgery, London, England. Inhaled oxygen at 100%, 12 L/min, delivered by face mask, for 15 minutes at the start of an attack of cluster headache or high-flow air placebo delivered alternately for 4 attacks. The primary end point was to render the patient pain free, or in the absence of a diary to have adequate relief, at 15 minutes. Secondary end points included rendering the patient pain free at 30 minutes, reduction in pain up to 60 minutes, need for rescue medication 15 minutes after treatment, overall response to the treatment and overall functional disability, and effect on associated symptoms. Fifty-seven patients with episodic cluster headache and 19 with chronic cluster headache were available for the analysis. For the primary end point the difference between oxygen, 78% (95% confidence interval, 71%-85% for 150 attacks) and air, 20% (95% confidence interval, 14%-26%; for 148 attacks) was significant (Wald test, chi(5)(2) = 66.7, P < .001). There were no important adverse events. Treatment of patients with cluster headache at symptom onset using inhaled high-flow oxygen compared with placebo was more likely to result in being pain-free at 15 minutes. isrctn.org Identifier: ISRCTN94092997.