Zolmitriptan is a 5-HT1B/1D receptor agonist for the acute treatment of 
migraine. This study examined the efficacy of a second dose of zolmitriptan for 
the treatment of persistent or recurrent headache. Part 1 was a randomised, 
placebo-controlled, double-blind evaluation of 2.5 mg and 5 mg zolmitriptan for 
the treatment of persistent migraine headache, two hours after an initial dose 
of 2.5 mg zolmitriptan. In part 2 (open-label), patients treated the first two 
attacks with 2.5 mg zolmitriptan, thereafter patients could treat any initial, 
persistent or recurrent migraine headache with 2.5 mg or 5 mg zolmitriptan. The 
unique design of this trial allowed patients to adjust their treatment to attain 
maximum headache relief and control of their disease. Of 2800 patients treating 
an initial migraine headache in Part 1, 989 patients took a second dose to treat 
persistent headache of moderate or severe intensity. Headache response rates 
were similar across the three treatment groups, but the pain-free response rate 
was significantly higher with 5 mg zolmitriptan than with placebo (p < 0.001). 
In Part 2, 2499 patients treated 49,784 migraine attacks (excluding the first 
two attacks, which had to be treated with 2.5 mg zolmitriptan), of which 66% 
required only a single dose of zolmitriptan. Patients treated 22% of attacks 
with a second dose of zolmitriptan for persistent headache. A headache response 
was achieved in 80% and 73% of persistent headaches treated with 2.5 mg or 5 mg 
zolmitriptan, respectively. Corresponding pain-free responses following 
treatment of persistent headaches of any intensity were 64% and 52%. Eight per 
cent of attacks were treated with a second dose of zolmitriptan for moderate or 
severe recurrent headache. A headache response was achieved in 90% and 86% of 
moderate/severe attacks, with a pain-free response in 78% and 70% of attacks of 
any intensity treated with 2.5 mg and 5 mg, respectively. Zolmitriptan was well 
tolerated. In conclusion, 2.5 mg and 5 mg zolmitriptan are highly effective in 
treating both persistent and recurrent migraine headache.