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The Scientific Basis of Medication Choice in Symptomatic Migraine Treatment*

Published online by Cambridge University Press:  02 December 2014

Peter J. Goadsby
Peter J. Goadsby*
Affiliation:
Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London UK
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Abstract:

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With the rapid advances in the treatment of acute attacks of migraine in the last few years and a number of new treatments, has come the practical clinical problem of comparing emerging acute attack therapies alone and with regard to current treatments. Acute migraine therapies can usefully be regarded as non-specific and specific, from the perspective of migraine, since some medicines, such as aspirin or paracetamol, are used to treat pain more broadly. In this review I will compare both non-specific and specific compounds. To some extent the introduction into trial then clinical use of sumatriptan, the first of the 5HT1B/1D agonists or triptans, brought new standards in both clinical trial design, and execution and clinical outcome. Thus sumatriptan has become the de facto gold standard and will be thus employed here. To be practical the discussion of the new triptans will be limited to those available widely, naratriptan, rizatriptan and zolmitriptan. There are two broad issues when comparing treatments: what end-point should be considered and then, how can different compounds be compared with respect to that end-point. In terms of end-points those used here relate to pain relief because they have been collected robustly in the clinical studies and, fortunately, rapid pain relief is what patients questioned in population-based studies rate highest in an acute attack medicine. Headache pain has been rated on a scale of nil, mild, moderate and severe and success rated as either a response, nil or mild pain, or headache free, nil pain, at two or four hours. The ideal comparison of the triptans would be a randomized controlled clinical trial directly comparing the medicines in each case. Given that these are not available for all the compounds and the well characterised placebo response in acute migraine studies, summary measures have been developed to express the differences between compounds to try and adjust for the varying placebo effect. The two most widely used are the therapeutic gain, response on active medication minus response on placebo, and the number-needed-to-treat (NNT). The NNT is the reciprocal of the therapeutic gain as a proportion. The strengths and weaknesses of this approach will be discussed, including the importance of the calculation of confidence intervals. It can be concluded that our current instruments are rather blunt and patient preference needs much greater study.

Résumé

RÉSUMÉ

Avec les progrès rapides dans le traitement des accès aigus de migraine au cours des dernières années et l’avènement de plusieurs nouveaux médicaments, nous faisons face au problème clinique pratique de l’évaluation de ces nouveaux médicaments par rapport aux médicaments usuels. Les médicaments utilisés pour traiter la crise aiguë de migraine peuvent être divisés à toute fin pratique en médicaments non spécifiques et spécifiques du point de vue de la migraine, certains médicaments tels l’aspirine ou le paracétamol étant utilisés pour traiter la douleur en général. Dans cette revue du sujet, les médicaments non spécifiques et spécifiques seront comparés. Jusqu’à un certain point, les essais cliniques puis l’utilisation courante du sumatriptan, le premier des agonistes du 5HT1B/1D ou triptans, a entraîné l’établissement de nouveaux standards tant dans la conception et l’exécution des essais cliniques que dans les critères d’efficacité clinique. Le sumatriptan est donc devenu de facto l’étalon or et sera ainsi considéré dans cet article. Sur le plan pratique, la discussion des nouveaux triptans sera limitée à ceux qui sont largement disponibles, soit le naratriptan, le rizatriptan et le zolmitriptan, avec quelques références à l’élétriptan qui sera disponible bientôt. Il y a deux grandes questions quand on compare des médicaments: quels critères d’efficacité clinique devraient être utilisés et comment différents produits peuvent être comparés quant à ces critères. Pour ce qui est des critères d’efficacité, ceux qui sont utilisés ici touchent le soulagement de la douleur parce qu’ils ont été recueillis avec robustesse au cours des études cliniques et, fort heureusement, le soulagement de la douleur est ce à quoi les patients interrogés dans les études de population attachent le plus d’importance pour un médicament utilisé dans le traitement d’une crise aiguë. La céphalée a été classifiée sur une échelle allant de nulle, à légère, modérée ou sévère, et le succès a été évalué soit comme une réponse, douleur nulle ou légère, ou sans céphalée, douleur nulle, à 2 ou 4 heures. La comparaison idéale des triptans serait une étude clinique randomisée, contrôlée, comparant directement les médicaments chez chaque patient. Comme ces études ne sont pas disponibles pour toutes les substances et qu’il existe un effet placebo bien caractérisé dans les études sur l’accès aigu de migraine, des mesures sommaires ont été développées pour exprimer les différences entre les substances et pour essayer d’ajuster pour différents effets placebo. Les deux méthodes les plus utilisées sont le gain thérapeutique, la réponse lorsque le patient prend le médicament actif moins la réponse sous placebo, et le nombre de patients devant être traités (NPT). Le NPT est la réciproque du gain thérapeutique exprimé sous forme de proportion. Les forces et les faiblesses de cette approche sont discutées, incluant l’importance du calcul des intervalles de confiance. On peut conclure que les instruments dont nous disposons actuellement sont plutôt frustres et que la préférence des patients doit être étudiée plus à fond.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 26 , Issue 3 , November 1999 , pp. 20 - 26
Copyright
Copyright © The Canadian Journal of Neurological 1999

Footnotes

*

Modified from1

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