A new subclassification of primary headache, trigeminal autonomic cephalgia, incorporates cluster headache with several other rarer types of headache that can be difficult to distinguish from primary cluster headache.8 Differentiation is important because the non-cluster types respond dramatically to indomethacin, whereas cluster headaches do not (TABLE 1).9
TABLE 1
Source of cluster headaches
| FEATURE | CLUSTER | MIGRAINE | PAROXYSMAL HEMICRANIA | SUNCT* | HEMICRANIA CONTINUA |
|---|---|---|---|---|---|
| Duration | 15–180 min | 4–72 hrs | 2–30 min | 5–240 sec | Continuous |
| Autonomic dysfunction | Yes | Unusual | Yes | Yes | Sometimes |
| Pain quality | Sharp, boring | Often pulsatile | Stabbing or Stabbing | Stabbing or pulsatile | Stabbing or pulsatile |
| Severity | Severe | Mod–severe | Severe | Severe | Mod–severe |
| Frequency | Predictable | Varies | >5/day | 3–200/day | Continuous |
| Laterality | Unilateral | Varies | Unilateral | Unilateral | Unilateral |
| Response to Indomethacin | Not usually | Not usually | Always | Always | Always |
| *SUNCT, short-lasting neuralgiform headache attacks with conjunctival injection and tearing. | |||||
| Source: Lipton et al, Neurology 2004.4 | |||||
The 2 goals of treatment
Terminating acute headache is the first goal; shortening or aborting the cluster cycle is the second.
Research in the treatment of cluster headaches has been hampered by the relative infrequency of the condition, the short duration of each episode, and a robust placebo response.10 Much of the available evidence for the efficacy of various treatments comes from small controlled studies and case series.
Episodic cluster headaches respond much more readily to therapy than do chronic cluster headaches. Remember that no single intervention will work for every patient, and that some options are highly effective only for a small percentage of patients.
Of the drugs discussed in this section, injectable sumatriptan for acute attacks and oral verapamil for prophylaxis of attacks have the best evidence of efficacy based on controlled clinical trials.11
Terminating acute headaches
100% oxygen. One hundred percent oxygen, delivered by face mask at high flow rates, has been shown to reduce the severity of cluster headaches or terminate acute attacks (TABLE 2). Absence of side effects is the real advantage of this therapy; the major drawback is the lack of portability of an adequate oxygen supply (strength of recommendation [SOR]: B). 22
Triptans. Subcutaneous sumatriptan has been shown to provide relief for 88% of users (number needed to treat [NNT]=2.1), and its effectiveness seems not to wane with repeated use. The preferred dose is 6 mg; higher doses have been studied and are no more effective (SOR: A).23 Intranasal sumatriptan is also effective, although less so than the parenteral form (NNT=3.2).13 Oral zolmitriptan (Zomig) has shown benefit in approximately 60% of cases with both the 5- and 10-mg doses in episodic cluster headaches (NNT=5.6), but is no more effective than placebo in chronic cluster patients.15
Side effects. Most patients report side effects with triptans,24 the most common being “atypical sensations” such as tingling, heat, pressure, tightness, numbness, or flushing. Dizziness and sedation can also occur, and, with injectable sumatriptan, reactions at the injection site are common. Before prescribing injectable sumatriptan, supervise administration of the first dose.
Caveats. Triptans are contraindicated for patients with vascular disease (coronary artery disease, stroke, peripheral vascular disease), renal, or liver dysfunction. Triptans should be used with caution by persons with multiple risk factors for coronary disease. They cannot be used in combination with other triptans or within 24 hours of the use of dihydroergotamine (DHE 45).25
Dihydroergotamine. DHE can be used to terminate acute attacks using intravenous, subcutaneous, or intramuscular routes of administration (SOR: B). The usual dose is 1 mg, and many clinicians administer 10 mg of metoclopramide (Reglan) simultaneously to counter nausea (SOR: C). Complete familiarity with the proper use and potential adverse effects of injectable DHE is critical before using it in the outpatient setting.
Like triptans, DHE is contraindicated for those with vascular disease or severe liver or kidney impairment. Side effects include numbness or tingling in the extremities, muscle cramps, palpitations, and pain or tightness in the chest. Pleural and retroperitoneal fibrosis has occurred following prolonged daily use of ergots, and the use of DHE in patients with unrecognized coronary artery disease has caused death.
DHE levels are elevated by concurrent use of cytochrome P450 3A4 inhibitors such as macrolide antibiotics, protease inhibitors, ketoconazole, and itraconazole.26
Other abortive agents. There is little evidence for the use of other abortive agents. This poses a significant problem for the patient with cluster headaches who cannot take vasoconstrictors. A study of 5 patients showed olanzapine (Zyprexa), 2.5 to 10 mg, is a potentially effective abortive agent,27 and a larger study showed that octreotide (Sandostatin), 100 μg subcutaneously, relieved 52% of cluster headaches (NNT=6.3).16 Intranasal lidocaine has been shown to provide relief for 55% of migraine headaches, and some recommend its use in cluster headache.28