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Management of Cluster Headaches With Triptans

Route of administration can be the difference

Cluster headaches are headaches that are painful and produce symptoms unilaterally. The term cluster headache describes the frequency of attack, which can be anywhere from one to eight times a day. Each headache lasts 15 to 180 minutes.1

Cluster headaches are the second most common primary headache disorder seen by a neurologist or headache specialist. Other primary headache disorders include migraine with or without auras and tension type headaches. Ensuring the correct diagnosis of the primary headache disorder is important to ensuring that treatment therapy of the patient's headache is effective.

Cluster headaches occur in two forms: episodic attacks in which the patient is headache-free for a month or more without the need for therapy (80% of patients) and chronic cluster headaches in which the patient does not experience headache-free periods (20% of patients).2 The management of cluster headaches involves treatment of the acute attacks and prevention of the attacks.2 Several treatment options for cluster headaches have been explored, including oxygen, triptans and nasal sprays. Triptans are significantly more effective than placebo in the treatment of acute cluster headaches.3

Cluster headaches affect approximately 1% of the population, with a male:female ratio of about 2.7-7.1:1. First-degree relatives of cluster headache patients have a 14-fold to 39-fold increased risk of cluster headache.3 The average onset of the condition is mid-20s to early 30s, however, earlier or later onset is not uncommon.4 Five percent of patients with cluster headaches have an autosomal dominant condition.3 Therefore, cluster headaches have a lower degree of genetic inheritance.

The exact cause of cluster headaches is unknown. The unilateral nature of these headaches and the occurrence of the attacks, usually during sleep, have led researchers to believe the posterior hypothalamic grey matter could be the origin.4 Cluster headaches are more common in smokers, with triggers including alcohol use, nitroglycerin use, hypoxic conditions, changes in sleeping habits such as naps during the day, and strong smells.

Diagnostic Criteria
A diagnosis of cluster headache can only be made when the patient experiences attacks that meet the criteria developed by the International Headache Society:5 severe or very severe unilateral orbital, supraorbital or temporal pain that lasts for 15 to 180 minutes if untreated. This pain is accompanied by at least one of the following: ipsilateral symptoms (conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis or eyelid oedema); attacks with a frequency of once every other day to eight times a day; and symptoms that are not associated with any other disorder.

Treatment with Triptans
Triptans have been broadly studied for the acute treatment of migraines. Triptans are agonists of serotonin and 5-HT1D receptors. Serotonin receptors are found on blood vessels and 5-HT1D receptors are found on sensory nerves. Triptans are thought to work in three ways by preventing the release of CGRP and substance P from the trigeminal nerve, modeling of second-order neurons centrally in the trigeminal pathway, and vasoconstriction.6

SEE ALSO: The Functional and Emotional Effects of Migraine

Triptans, available in oral, intranasal and subcutaneous forms, have been studied for use in cluster headaches due to the relationship shared between the clinical features of migraines and cluster headaches.7 The use of triptans in the treatment of cluster headaches is a safe alternative for acute attacks.3 Another triptan delivery option is high-flow oxygen, however the method of choice is subcutaneous sumitriptan or zolmitriptan nasal spray, since these are more practical and convenient options. Triptans are also available as an orally disintegrating tablet. Subcutaneous sumitriptan provides patients with the fastest relief and 1- to 2-hour headache relief, making it the most effective route for patients who can tolerate an injection.6

Research Results of Triptan Use
A Cochrane review of triptan treatment for cluster headaches analyzed six research studies that satisfied the inclusion criteria set by the authors. The inclusion criteria were as follows: randomized, double-blind, placebo-controlled or active controlled studies that used a triptan medication to treat a cluster headache episode.7

The headache in all of the studies was described as at least moderate intensity, and all studies compared the triptan medication with a placebo. The studies looked at the use of zolmitriptan, sumatriptan and the placebo. The proportion of patients with cluster headache attacks that were pain free at 15 minutes with the use of zolmitriptan nasal spray 5 mg was 8%. The proportion of patients with cluster headache attacks that were pain-free with the placebo was 3%.

The pain from the cluster headache was evaluated again at 30 minutes. Of the participants who received zolmitriptan, 32% reported being pain-free and 18% of patients who received the placebo reported being pain-free. The percentage of participants reporting headache relief at 15 minutes was 15% in the zolmitriptan group and 7% in the placebo group. The headache relief reported at 30 minutes was 50% in the zolmitriptan group and 35% in the placebo group.

The proportion of cluster headache patients who were pain-free at 15 minutes with the use of sumatriptan (subcutaneous) 6 mg was 48%; 17% of placebo patients were pain-free at 15 minutes. The proportion of headache relief reported at 15 minutes was 75% in the sumatriptan group and 32% in the placebo group.7

Alternative Treatments
Several studies have been completed on the use of botulinum toxin as treatment for chronic headaches not relieved by oral therapies. One study looked at men and women ages 18 to 65 who experienced episodic and chronic migraine. Patients were excluded if they had medical conditions that would not allow exposure to botulinum toxin. The treatment types researched were BoNTA injections, a placebo BoNTA and divaproex sodium (DVPX) therapy. BoNTA and placebo BoNTA were injected at a concentration of 25 U/mL. The participants not receiving the BoNTA injections received the DVPX treatment. The participants were evaluated 1 month and 3 months after the first injection, and the participants were evaluated again 3 months and 6 months after the second injection (6 months and 9 months after receiving the initial treatment).

Participants who received the BoNTA injections had significant reduction in their headaches at the 1-, 3-, 6- and 9-month evaluations. Patients who received placebo BoNTA and DVPX therapy also had significant reduction in their headaches at months 1, 3, 6 and 9.8 This study was one of the first studies to examine BoNTA and the FDA-approved DVPX. The main limitation of the study was the small sample size. However, the findings suggest that prophylactic treatment with BoNTA and DVPX for patients with chronic and episodic migraine is effective in reducing the disability associated with migraines.8

Deciding on Treatment
The first step in diagnosing a patient with cluster headaches is to obtain a thorough health history and a complete history of symptoms to ensure the headaches are in fact cluster headaches. Determine if the patient has previously been treated for cluster headaches and the treatment choices and outcomes. Based on the information gathered, start the patient with the least invasive treatment, such as a triptan, to determine whether it will provide relief during an episodic attack. Advise the patient to stop smoking if he or she is a smoker, to avoid alcohol use, to avoid changes in sleep patterns (i.e., napping during the day), and to avoid strong odors when possible. These lifestyle factors are triggers of cluster headaches, and eliminating these triggers can help reduce the occurrence of an attack.

At follow-up, if triptan use is unsuccessful, look to alternative routes of administration for the triptan medication. If the patient was started on an oral triptan, try an intranasal route or suggest a subcutaneous injection. If these alternative routes are still not effective in relieving the headache episode, look into treatment with other alternative therapies such as botulinum toxin injections.

Natasha Lamach is a family nurse practitioner at Avecina Medical in Jacksonville, Fla.

1. Edwards J. Diagnosis and management of cluster headache. Nurse Prescribing. 2012;10(12):590-596.

2. Goadsby P. Treatment of cluster headache. American Headache Society.

3. Pageler L, Limmroth V. Oral triptans in the preventive management of cluster headache. Curr Pain Headache Rep. 2012;16(2):180-184.

4. Braine ME. Cluster headache. Brit J Neurosci Nurs. 2013;9(1):8-9.

5. International Headache Society. HIS Classification the Primary Headaches.

6. Johnston MM, Rapoport AM. Triptans for the management of migraine. Drugs. 2010;70(12):1505-1518.

7. Law S, et al. Triptans for acute cluster headache. Cochrane Database Syst Rev. 2013;7:CD008042.

8. Blumenfeld AM, et al. Botulinum toxin type a and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache. 2008;48(2):210-220.

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