Key words: Migraine; clinical trials; neurotherapeutics; triptans; allodynia; placebo effects; responder rates.

Introduction

Migraine is a common neurovascular disorder characterised by recurrent attacks of moderate to severe headache with nausea and/or photo- and phonophobia. Triptans, selective serotonin 5-HT1B/1D agonists, are specific acute migraine drugs of which efficacy and safety are well established in numerous clinical trials (Goadsby et al., 2002; Ferrari et al., 2001). Efficacy is usually presented as the response rate, the proportion of patients whose headache improved from severe or moderate pain at baseline to mild or no pain at 2-h post-dose (Figure 1) (Tfelt-Hansen et al., 2000). Consequently, in clinical trials of triptans in acute migraine, patients have traditionally been required to take their medication only when their pain had reached a moderate or severe intensity. There are good methodological reasons for this somewhat artificial design. If patients wait until a moderate or severe pain level has been reached, it is more likely that true migraine headaches are being treated rather than a non-migraine (e.g. tension-type) headache (Tfelt-Hansen et al., 2000). Delayed treatment should also minimise the placebo response, allowing for spontaneous resolution of possible short, non-migraine headaches. It also simplifies the assessment of the improvement as all patients start from a similar level of baseline pain rather than from different levels: a shift from severe to moderate pain is not the same as improvement from mild to no pain.