Prevention and interruption of the cluster cycle
More important than aborting the acute headache is ending the cluster episode.
Verapamil. Ample evidence supports the effectiveness of verapamil (Calan) for this purpose (NNT=1.2).17 Larger doses than are typical for hypertensive therapy may be required.
Cluster headache demographics
Cluster headache, the most severe primary headache, is rare compared with other types of headache. Thus, despite severe head pain, the diagnosis may be overlooked.6 Studies in which the diagnosis was clinically confirmed reveal a prevalence ranging from 56 to 381 cases per 100,000 people.29 Cluster differs from migraine in that men are affected more commonly than women. Once believed to have a gender differential of 6:1, the ratio is now reported at 3.7:1.6
Age of onset also contrasts with migraine. Cluster headaches typically begin at around 30 years of age with a range of 20 to 50 years, but rarely as old as 80 years. Women are more likely than men to have onset in later years.
Most patients are smokers or former smokers (74%), but cessation of smoking does not appear to modify the pattern of headaches.
Inheritance plays a greater role than previously realized, suggesting a genetic cause. First-degree relatives have a 5- to 18-fold higher risk for cluster headache than the general population. Second-degree relatives have a 1- to 3-fold higher risk. The mode of inheritance is likely autosomal dominant with low penetrance in some families, and multifactoral inheritance or autosomal recessive in other families.29
A regimen of 40 mg in the morning, 80 mg at noon, and 80 mg at bedtime, allowing patients to titrate doses up by 40 mg on alternate days, relieved 94% of episodic cluster headaches and 55% of chronic cases (SOR: B).30 Most patients need 200 to 480 mg/d to achieve success, but some require up to 960 mg/d.30
If a patient is asymptomatic but has a history consistent with cluster headaches, and if your examination reveals no other cause of headache, a trial of verapamil is warranted to abort the cluster cycle or prevent additional cycles.
Other agents. Corticosteroids may act faster than verapamil, and the two can be used in combination (SOR: C). A typical regimen of prednisone starts with 40 mg/d and tapers over 3 weeks.28
Lithium (Lithobid, Eskalith) is effective, but acts slowly and causes more side effects than other agents.20
Other agents that have shown efficacy in small studies are gabapentin, baclofen, clonidine, twice daily eletriptan, and topiramate.31-34
Sodium valproate (Depakote) is also used prophylactically for both cluster and migraine headaches. One small study demonstrated efficacy, but a larger trial failed to show benefit due to a unexpectedly high placebo response rate.35,36
When to refer
Treatment for most cluster headache sufferers is adequately handled in the primary care setting. When medical therapy fails, consider referral to a headache specialist, particularly for those with chronic cluster headaches. In some cases, sympathetic nerve blockade might be a worthwhile consideration.37 Unfortunately, a small subset of patients will not find relief regardless of the regimen employed.
TABLE 2
Selected cluster headache trials
| DRUG | RESPONSE | # OF PTS | NNT |
|---|---|---|---|
| Sumatriptan 6 mg subcut. vs placebo12 | 74% response @ 15 min 26% placebo response | 39 | 2.1 |
| Sumatriptan nasal vs placebo13 | 57% response @ 30 min 26% placebo response | 118 | 3.2 |
| Sumatriptan subcut. vs sumatriptan nasal14 | 94% response to injection @ 15 min 13% response to nasal | 49 | 1.2 |
| Zolmitriptan 10 mg orally vs placebo15 | 47% response @ 30 min 29% placebo response | 124 | 5.6 |
| Octreotide 100 μg subcut. vs placebo16 | 52% response @ 30 min 36% placebo response | 46 | 6.3 |
| Verapamil 120 mg orally 3× daily vs placebo17 | 80% response in 2nd week | 15 each arm | 1.2 |
| Oxygen 100%18 | 75% with significant pain relief within 15 min | 52 | — |
| Dihydroergotamine IV19 | 73% relief refractory episodic cluster | 60 | — |
| 63% relief refractory chronic cluster | 37 | — | |
| Lithium 900 mg daily vs Verapamil 360 mg daily20 | Lithium: 37% improve in 1st week Verapamil: 58% improve in 1st week | 24 | 4.8 |
| Eletriptan 40 mg twice daily×6 days21 | 40% fewer attacks | 16 | — |
CORRESPONDENCE
Stephen Adams, MD, 1100 East Third Street, Chattanooga TN 37403. E-mail: stephen.adams@erlanger.org