Q What are your abortive treatment options for chronic cluster headache? What are your preventive choices?
The abortive regimens used by our panelists for treatment of chronic cluster headache were similar all around. "In my opinion, abortive treatment should be chosen on a case-by-case basis according to efficacy and side effects profile," Armando Perrotta, MD says. "In my experience, subcutaneously or orally administered sumatriptan represents the most effective treatment." These are sentiments echoed by Paolo Rossi, MD, PhD and Alexander Mauskop, MD, who each say they administer up to 6mg sumatriptan; with as many as three injections per day, according to Dr. Rossi.

"However, eletriptan 40mg or 80mg represents an effective alternative therapy in several patients who failed to respond to sumatriptan," Dr. Perrotta says. Dr. Mauskop rounds out his catalog of abortive options with oxygen at 8-10 liters/min via mask and Zomig NS at 5mg.

The panel was also largely in lockstep over which preventive options they choose, though they differed in dosing. Because, "the preventive treatment needs to be drafted on a rapidly acting therapy," Dr. Perrotta says, it's based on a corticosteroid (he suggests prednisone 50mg daily), and on a long-lasting therapy usually based on verapamil (from 240-520mg daily, he says) or carbolithium (from 300-1200mg daily). "Recently, promising results are coming from topiramate 100mg daily as adjunctive treatment."

Dr. Rossi favors administering verapamil from 320-720mg per day, lithium carbonate from 600-900mg per day, and topiramate from 75-100mg as an adjunct. If the patient can tolerate high doses of verapamil, Dr. Mauskop advocates going as high 1200mg a day, "but before every increase an EKG needs to be checked [because] it can cause cardiac conduction block."

For some patients with chronic cluster headache, surgery is a last-resort for medication refractory patients, according to Stephen Landy, MD. These procedures can be divided between destructive and neuromodulatory options. Destructive options include trigeminal sensory rhizotomy, radiofrequency trigeminal gangliorhizolysis, gamma knife radiotherapy, and microvascular decompression of the nervus intermedius. Neuromodulatory options include posterior hypothalamic neurostimulation and occipitial nerve stimulation.

Q When do you consider pure oxygen therapy? What dosing would you recommend to patients? What are some problems that come with oxygen intake, be it therapeutically or device-oriented?
"Oxygen therapy should be always considered as alternative to acute treatment, also if the efficacy rate is lower when compared to triptans," Dr. Perrotta says. "I always try oxygen in every patient because it is well tolerated and allows to save Imigran [sumatriptan] doses," Dr. Rossi says. "I consider pure oxygen therapy for those patients responding to it and having attacks at the times they are at home (e.g nocturnal)." The dose most recommend by the panel was 7-10 liters/min 100% for maximum 15 minutes while seated and leaning forward.

While there are no large complaints of side effects, our panel members did make an issue over oxygen's efficacy. "Oxygen treatment," Dr. Perrotta says, "is frequently ineffective or only postpones the attack without a real abortive capacity."

Patients encounter difficulties with the devices that are not adequate to provide a 100% flux, Dr. Rossi says, and adds that a group of patients experiences an early recurrence of the attack after oxygen and it may increase, paradoxically, the frequency of CH attacks. Dr. Mauskop worries about a device-oriented side effect. "The only problem is the risk of explosion from an open fire, which is a real concern since many cluster patients smoke," he says.

Q Would you consider using Sansert? If so, when and under what circumstances? How can a patient obtain it, since it is FDA-approved but not for sale in the US?
Methysergide is an oral, synthetic ergot alkaloid, structurally related to the oxytocic agent methylergonovine and to the potent hallucinogen LSD.1 It is used prophylactically, and while methysergide is an ergot alkaloid, it is a weak vasoconstrictor and oxytocic. Methysergide is a more potent antagonist of peripheral serotonin receptors than other ergot alkaloids.

"Methysergide, as other preventive treatment (i.e. carbolithium), was not tested in controlled trials and data on its efficacy is, in general, anecdotal. It could be taken into account in case of intractable forms when other treatments are ineffective," Dr. Perrotta says. "We consider using Sansert primarily for refractory episodic cluster headache patients," Dr. Landy says, "because their cycles are usually less than four months and thus less likely to be associated with fibrotic complications. Patients can obtain it from Canada."

Dr. Mauskop chooses not to use the drug, since it's not available in the US and it carries serious side effect risks, notably retroperitoneal fibrosis. In their piece, Koehler and Tfelt-Hansen2 note the rise, fall, and subsequent use as a third-choice drug of the first effective migraine prophylactic was largely because of this serious side effect. "Based on the possible involvement of serotonin in migraine attacks, it was introduced in 1959 by Sicuteri as a preventive drug for migraine," they write. "The clinical effect was often excellent, but five years later it was found to cause retroperitoneal fibrosis after chronic intake. Consequently, the use of the drug in migraine declined considerably."

After administration, methysergide is rapidly absorbed and widely distributed throughout the body and possibly into breast milk with onset of action occuring within one to two days.1 Metabolism of the drug is mainly hepatic, producing methylergonovine and glucuronide metabolites. About 56 percent of a dose is excreted in the urine unchanged and as metabolites. The drug has a half-life of about 10 hours.

Dosing recommended in adults is 4-8mg PO daily for up to six months.1 A drug-free interval of three to four weeks should follow each six-month course of treatment. Dosage should be gradually reduced in the two to three week period before the start of the drug-free period. A 1965 study found that about 4mg of Sansert is equal to 25mcg of LSD.3

Q Medication overuse can become a problem in cluster headaches. What are your treatment options when this occurs?
Medication overuse headache in cluster patients is more likely to occur in cluster patients with a clear personal or family history of migraine, Dr. Landy says. Abortive treatment options for these patients include subcutaneous sumatriptan and oxygen and avoidance of acute treatments not supported by the evidence for cluster headache, including opiates, combination analgesics, and oral triptans. "Preventive therapy is also recommended to minimize the risk of development of medication overuse headache," he says.

In his experience, Dr. Perrotta says medication overuse headache, as recognized in migraine subjects, is very rare in patients with a pure form of cluster headache. It can occur in patients with concomitant diagnosis of cluster headache and migraine, in which the intake of triptans on a daily basis for cluster headache pain can lead to a typical medication overuse headache as a complication of the migraine condition, he says. In these patients, he feels, the withdrawal treatment could not be practicable during the cluster period, and a concomitant preventive treatment for migraine (valproate, topiramate or other) should be used.

Dr. Mauskop has seen medication overuse get out of hand: "I've had patients having rebound from Imitrex injections with several patients taking 10 injections a day. These patients often need to be hospitalized and given IV dihydroergotamine or histamine desensitization."

Stephen Landy, MD is at the Wesley Headache Clinic and Clinical Professor of Neurology at University of Tennessee School of Medicine.

Alexander Mauskop, MD is a specialist at the New York Headache Center.

Armando Perrotta, MD is a headache specialist in Pozzilli (Isernia), Italy.

Paolo Rossi, MD PhD is a headache specialist in Grottaferrata (Rome), Italy.