STAMFORD, Conn. -- For cluster headaches with their intractable pain, intranasal zolmitriptan (Zomig) may be an effective addition to the slim armamentarium against the condition, researchers said.
STAMFORD, Conn., Aug 27 -- For cluster headaches with their intractable pain, intranasal zolmitriptan (Zomig) may be an effective addition to the slim armamentarium against the condition, researchers said.
In a 52-patient randomized crossover trial, a 10-mg dose relieved headaches better than placebo starting within 10 minutes of dosage (P<0.05), reported Alan M. Rapoport, M.D., of the New England Center for Headache here, and colleagues.
By 20 minutes a 5-mg dose was superior to placebo (P<0.01), they added, in the Aug. 28 issue of Neurology.
The findings demonstrated "that a fast onset of efficacy is possible with a drug that is not delivered parenterally," they wrote, adding that the nasal spray "could be considered as first-line therapy in appropriate patients for the acute treatment of this disease."
Cluster headache, though relatively rare, is considered the most intense primary headache disorder. Pain typically peaks within five minutes and remains severe for 30 to 180 minutes.
But, the only FDA-approved acute treatment for cluster headache is subcutaneous sumatriptan (Imitrex) and few medications have been systematically tested for the disorder, leaving "enormous unmet treatment needs," Dr. Rapoport and colleagues wrote.
So following a European study that found zolmitriptan nasal spray effective for cluster headaches, the researchers conducted a double-blind, crossover study comparing 5 and 10 mg doses.
The four-center study included 52 patients (14 women) with episodic or chronic cluster headaches. Five milligrams of zolmitriptan was given for 52 attacks, 10 mg zolmitriptan for 49, and placebo for 50.
Once pain reached at least a moderate severity, participants were to record headache pain intensity and immediately spray the medication once in each nostril. They were allowed escape medication (oxygen, lidocaine, or a non-triptan analgesic) after an hour.
For the primary endpoint, 63.3% of patients with attacks treated with 10 mg of zolmitriptan reported their pain faded to mild or moderate levels at 30 minutes (P<0.01 versus placebo), compared with 50% of patients receiving the 5-mg dose (P<0.05 versus placebo) and 30% of those receiving placebo.
Neither dose relieved headaches better than placebo at five minutes, but the higher zolmitriptan dose was more effective than placebo at 10 minutes (24.5% versus 10%, P<0.05) and 15 minutes (38.8% versus 14%, P<0.05).
By 20 minutes, the lower dose had improved on placebo for headache relief as well (38.5% versus 20%, P<0.01).
By one hour, only the higher dose remained better at headache relief than placebo (79.6% versus 56%, P<0.05).
"This in part is expected because the median duration of cluster headache attacks is shorter than 60 minutes," the researchers said, and partly because the study lost statistical power by a smaller than anticipated number of patients completing the study.
For a secondary outcome of the percent of patients pain free, the same pattern was seen. The higher dose was better than placebo at 15 minutes (P<0.05), both doses were superior at 20 minutes (P<0.05) and at 30 minutes (P<0.01), and only the high dose was better than placebo at one hour (P<0.05).
Rescue medication use was no different between groups, and adverse events were as expected for a triptan medication.
The study was limited by loss of more patients than expected to follow-up or withdrawn consent. Also, generalizability may be limited because all patients were recruited from headache specialty centers, which are more likely to have treatment refractory patients.
The researchers also warned that zolmitriptan is not FDA approved for 10-mg as a single dose for any indication, and is approved only for acute treatment of migraine in adults.
Nevertheless, for physicians considering using intranasal zolmitriptan for cluster headache, Dr. Rapoport and colleagues suggested, "the initial dose should be based on the attack-related disability, number of cluster attacks per day, and the patient's history of triptan tolerability."
"For those with very severe attacks occurring only once per day or every other day, 10 mg may be the optimal initial dose," they added. "For those with more frequent attacks or poor tolerability, 5 mg should be the initial dose."