Triptans for acute cluster headache Stable (no update expected for reasons given in 'What's new')
This is an updated version of the original Cochrane review published in Issue 4, 2010 (Law 2010). Cluster headache is an uncommon, severely painful, and disabling condition, with rapid onset. Validated treatment options are limited; first‐line therapy includes inhaled oxygen. Other therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and they may also be useful for cluster headache.
To assess the efficacy and tolerability of the triptan class of drugs compared to placebo and other active interventions in the acute treatment of episodic and chronic cluster headache in adult patients.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, and reference lists for studies from inception to 22 January 2010 for the original review, and from 2009 to 4 April 2013 for this update.
Randomised, double‐blind, placebo‐controlled studies of triptans for acute treatment of cluster headache episodes.
Data collection and analysis
Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief, requiring rescue medication, and experiencing adverse events and headache‐associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat for benefit (NNT) and harm (NNH).
New searches in 2013 did not identify any relevant new studies.
All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. Subcutaneous sumatriptan was given to 131 participants at a 6 mg dose, and 88 at a 12 mg dose. Oral or intranasal zolmitriptan was given to 231 participants at a 5 mg dose, and 223 at a 10 mg dose. Placebo was given to 326 participants.
Triptans were more effective than placebo for headache relief and pain‐free responses. By 15 minutes after treatment with subcutaneous sumatriptan 6 mg, 48% of participants were pain‐free and 75% had no pain or mild pain (17% and 32% respectively with placebo). NNTs for subcutaneous sumatriptan 6 mg were 3.3 (95% CI 2.4 to 5.0) and 2.4 (1.9 to 3.2) respectively. Intranasal zolmitriptan 10 mg was of less benefit, with 12% of participants pain‐free and 28% with no or mild pain (3% and 7% respectively with placebo). NNTs for intranasal zolmitriptan 10 mg were 11 (6.4 to 49) and 4.9 (3.3 to 9.2) respectively.
Based on limited data, subcutaneous sumatriptan 6 mg was superior to intranasal zolmitriptan 5 mg or 10 mg for rapid (15 minute) responses, which are important in this condition. Oral routes of administration are not appropriate.
Simon Law, Sheena Derry, R Andrew Moore
Plain language summary
Triptans for acute cluster headache
Cluster headaches are excruciating headaches of extreme intensity. They can last for several hours, are usually on one side of the head only, and affect men more than women. Multiple headaches can occur over several days. Fast pain relief is important because of the intense nature of the pain with cluster headache.
Triptans are a type of drug used to treat migraine. Although migraine is different from cluster headache, there are reasons to believe that some forms of these drugs could be useful in cluster headache. Triptans can be given by injection under the skin (subcutaneously) or by a spray into the nose (intranasally) to produce fast pain relief.
The review found six studies examining two different triptans. The number of people in the studies was limited. Within 15 minutes of using subcutaneous sumatriptan 6 mg, almost 8 in 10 participants had no worse than mild pain, and 5 in 10 were pain‐free. Within 15 minutes of using intranasal zolmitriptan 5 mg, about 3 in 10 had no worse than mild pain, and 1 in 10 was pain‐free. Adverse events were more common with a triptan than with placebo but they were generally of mild to moderate severity.
Cluster headache is an awful thing to have. More research on how to get better pain relief faster, and to more patients, would be welcome.
Simon Law, Sheena Derry, R Andrew Moore
Implications for practice
Subcutaneous sumatriptan 6 mg provided headache relief and pain‐free outcomes within 15 minutes to many patients with cluster headache causing moderate or severe pain. Intranasal zolmitriptan 10 mg was distinguished from placebo but provided pain relief for few patients at early times. The need for fast delivery to deliver rapid relief in this condition effectively rules out oral administration.
Implications for research
The crucial factor in treating cluster headache is rapid delivery of the intervention or medicine. The methodological requirements are measurement of pain relief over a short time period, within 30 minutes, good methodological quality, and adequate size. Subcutaneous sumatriptan almost certainly be the standard active comparator because use of placebo is probably unethical in this severe condition.
Improvements in the formulation of triptans are unlikely to make a substantial difference to their early efficacy, given a history of formulation research over several decades. Studies comparing triptans with alternative therapy, such as inhaled oxygen, might be useful to determine relative benefits and harms. Combining optimum doses of triptan with oxygen, or with fast‐acting non‐steroidal anti‐inflammatory drug (NSAID) formulations (lysine, arginine, or sodium salts) (Derry 2009) might also be a useful line of research.
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