Triptans in migraine - A comparative review of pharmacology, pharmacokinetics and efficacy

Triptans are a new class of compounds developed for the treatment of migrai ne attacks. The first of the class, sumatriptan, and the newer triptans (zo lmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan and frovatrip tan) display high agonist activity at mainly the serotonin 5-HT1B and 5-HT1 D receptor subtypes. As expected for a class of compounds developed for aff inity at a specific receptor, there are minor pharmacodynamic differences b etween the triptans. Sumatriptan has a low oral bioavailability (14 %) and all the newer triptan s have an improved oral bioavailability and for one, risatriptan, the rate of absorption is faster. The half-lives of naratriptan, eletriptan and, in particular, frovatriptan (26 to 30 h) are longer than that of sumatriptan ( 2 h). These pharmacokinetic improvements of the newer triptans so far seem to have only resulted in minor differences in their efficacy in migraine. Double-blind, randomised clinical trials (RCTs) comparing the different tri ptans and triptans with other medication should ideally be the basis for ju dging their place in migraine therapy. In only 15 of the 83 reported RCTs w ere 2 triptans compared, and in ll trials triptans were compared with other drugs. Therefore, in all placebo-controlled randomised clinical trials, th e relative efficacy of the triptans was also judged by calculating the ther apeutic gain (i.e. percentage response for active minus percentage response for placebo). The mean therapeutic gain with subcutaneous sumatriptan 6 mg (51 %) was more than that for all other dosage forms of triptans (oral sum atriptan 100 mg 32 %; oral sumatriptan 50 mg 29 %; intranasal sumatriptan 2 0 mg 30 %; rectal sumatriptan 25 mg 31 %; oral zolmitriptan 2.5 mg 32 %; or al rizatriptan 10 mg 37 %; oral eletriptan 40 mg 37 %; oral almotriptan 12. 5 mg 26 %). Compared with oral sumatriptan 100 mg (32 %), the mean therapeu tic gain was higher with oral eletriptan 80 mg (42 %) but lower with oral n aratriptan 2.5 mg (22 %) or oral frovatriptan 2.5 mg (16 %). The few direct comparative randomised clinical trials with oral triptans reveal the same picture. Recurrence of headache within 24 hours after an initial successful response occurs in 30 to 40 % of sumatriptan-treated patients. Apart from naratriptan, which has a tendency towards less recurrence, there appears to be no consistent difference in recurrence rates between the newer triptans and sumatriptan. Rizatriptan with its shorter time to maximum concentratio n (t(max)) tended to produce a quicker onset of headache relief than sumatr iptan and zolmitriptan. The place of triptans compared with non-triptan drugs in migraine therapy r emains to be established and further RCTs are required.