Abstract
Dear sir We wish to comment on the recent article in which Klapper and O'Connor performed a blinded study to evaluate anecdotal reports that sublingual administration of rizatriptan wafer has increased effectiveness and greater speed of onset (1). A fundamental issue in this very small trial which found no treatment difference, is that it used a sample size of only 15 patients per group and was thus not powered to detect treatment differences. A previous study by Ahrens et al. (2) found that almost 45% of 188 patients who treated a moderate or severe headache with rizatriptan wafer placed on the tongue (as per the product label) experienced headache relief by 1 h, compared with 21% of 185 patients randomized to placebo (P < 0.01). A parallel design study using 15 patients per group has only 15% power to detect a 24% difference between groups. This low power provides ample opportunity to conclude that no difference exists between treatments when in fact one does exist.
Klapper and O'Connor suggest that their results should be replicated in further trials involving a larger number of patients and utilizing standard clinical trial methodology. We do not think that such trials are necessary. Our pharmacokinetic data on file indicate that no appreciable absorption of rizatriptan takes place via the oral mucosa. We therefore anticipate that there should be no efficacy benefit (or decrement) when administering rizatriptan sublingually vs. on the tongue. In an appropriately sized study, rizatriptan 10 mg wafer was more effective than placebo at relieving moderate or severe headache from 30 min after dosing (2).
We agree with Klapper and O'Connor that it can be useful to investigate the ‘real life’ efficacy of triptans, where patients are likely to treat at the onset of migraine pain rather than waiting until the pain is moderate or severe. A recent open-label study in 1919 migraineurs who treated with rizatriptan 10 mg tablets or wafers suggested that response rates within 1 h were greater in attacks that were treated at the onset of pain compared with attacks that were treated only when pain was moderate or severe (3). Thus, there may be an advantage to treating early in the attack.