The scientific basis of medication choice in symptomatic migraine treatment

With the rapid advances in the treatment of acute attacks of migraine in th e last few years and a number of new treatments, has come the practical cli nical problem of comparing emerging acute attack therapies alone and with r egard to current treatments. Acute migraine therapies can usefully be regar ded as non-specific and specific, from the perspective of migraine, since s ome medicines, such as aspirin or paracetamol, are used to treat pain more broadly. In this review I will compare both non-specific and specific compo unds. To some extent the introduction into trial then clinical use of sumat riptan, the first of the 5HT(1B/1D) agonists or triptans, brought new stand ards in both clinical trial design, and execution and clinical outcome. Thu s sumatriptan has become the de facto gold standard and will be thus employ ed here. To be practical the discussion of the new triptans will be limited to those available widely, naratriptan, rizatriptan and zolmitriptan. Ther e are two broad issues when comparing treatments: what end-point should be considered and then, how can different compounds be compared with respect t o that end-point. In terms of end-points those used here relate to pain rel ief because they have been collected robustly in the clinical studies and. fortunately, rapid pain relief is what patients questioned in population-ba sed studies rate highest in an acute attack medicine. Headache pain has bee n rated on a scale of nil, mild, moderate and seven and success rated as ei ther a response, nil or mild pain, or headache free, nil pain, at two or fo ur hours. The ideal comparison of the triptans would be a randomized contro lled clinical trial directly comparing the medicines in each case. Given th at these are not available for all the compounds and the well characterised placebo response in acute migraine studies, summary measures have been dev eloped to express the differences between compounds to try and adjust for t he varying placebo effect. The two most widely used are the therapeutic gai n, response on active medication minus response on placebo, and the number- needed-to-treat (NNT). The NNT is the I reciprocal of the therapeutic gain as a proportion. The strengths and weaknesses of this approach will be disc ussed, including the importance of the calculation of confidence intervals. It can be concluded that our current instruments are rather blunt and pati ent preference needs much greater study.