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Tourjman Smadar Valerie 200 Direction des bibliothèques AVIS Ce document a été numérisé par la Division de la gestion des documents et des archives de l’Université de Montréal. L’auteur a autorisé l’Université de Montréal à reproduire et diffuser, en totalité ou en partie, par quelque moyen que ce soit et sur quelque support que ce soit, et exclusivement à des fins non lucratives d’enseignement et de recherche, des copies de ce mémoire ou de cette thèse. L’auteur et les coauteurs le cas échéant conservent la propriété du droit d’auteur et des droits moraux qui protègent ce document. Ni la thèse ou le mémoire, ni des extraits substantiels de ce document, ne doivent être imprimés ou autrement reproduits sans l’autorisation de l’auteur. Afin de se conformer à la Loi canadienne sur la protection des renseignements personnels, quelques formulaires secondaires, coordonnées ou signatures intégrées au texte ont pu être enlevés de ce document. Bien que cela ait pu affecter la pagination, il n’y a aucun contenu manquant. NOTICE This document was digitized by the Records Management & Archives Division of Université de Montréal. The author of this thesis or dissertation has granted a nonexclusive license allowing Université de Montréal to reproduce and publish the document, in part or in whole, and in any format, solely for noncommercial educational and research purposes. The author and co-authors if applicable retain copyright ownership and moral rights in this document. Neither the whole thesis or dissertation, nor substantial extracts from it, may be printed or otherwise reproduced without the author’s permission. In compliance with the Canadian Privacy Act some supporting forms, contact information or signatures may have been removed from the document. While this may affect the document page count, it does not represent any loss of content from the document. Université de Montréal Évaluation pragnlatique de la quétiapine dans la dépression résistante aux antidépresseurs et efficacité' de la buspirone dans la dépression anxieuse par Smadar Valérie Tourjman Département de Pharmacologie Faculté de Médecine Mémoire présentée à la Faculté des études supérieures en vue de l'obtention du grade de Maître ès Science en Pharmacologie Septembre 2007 200ll' FEV.O} © Smadar Valérie Tourjman, 2007 Université de Montréal Faculté des études supérieures Ce mémoire intitulé: Évaluation pragmatique de la quétiapine dans la dépression résistante aux antidépresseurs et efficacité de la buspirone dans la dépression anxieuse Présenté par : Smadar Valérie Tourjman A été évalué par le jury suivant: P.- A. Lavoie, président-rapporteur R. Élie, directeur de recherche G. Rousseau, membre du jury 11 Résumé La dépression est une condition qui touche un grand nombre d'individus, ayant un impact personnel et social significatif. Différents sous-types de dépression avec une évolution et une thérapeutique distinctives ont été décrits, la dépression anxieuse étant la plus notable. La dépression résistante a aussi été proposée comme un sous-type de dépression. Dans les deux cas l'évolution défavorable constitue un défi clinique important. C'est cet enjeu qui a incité l'exploration en premier lieu de l'impact de l'anxiété sur la réponse au buspirone, un anxiolytique reconnu, et en deuxième lieu, de l'interaction possible de la quétiapine sur la dépreSSIon résistante. La première étude n'a permis de conclure aux effets possibles de l'anxiolytique à cause d'un effet placebo très marqué chez les sujets sélectionnés. La deuxième étude a montré un effet additionnel important de la quétiapine. Mots- clés: dépression. dépression anxieuse, dépression résistante, buspirone, fluoxétine, quétiapine, lithium III Abstract Depression is a condition affecting a large number of individuals, and having a significant personal and social cost. Various subtypes of depression have been described. Anxious depression figures prominently among these. It has also been proposed that resistant depression may be another subtype and in itself a specifie forrn of the illness. In both cases the unfavourable course poses a clinical challenge. It is this common element of poor treatment response that initially sparked the exploration of the impact of buspirone, a recognized anxiolytic, on the evolution of depression and subsequently that of quetiapine on depression resistant to antidepressant treatment. The first study was inconclusive due to the marked placebo response of the subjects. The second study showed a strong additive effect of quetiapine in the treatment of resistant depression. Keywords : depression. anxious depression, resistant depression, buspirone, fluoxetine, , quetiapine, lithium lV Table des matières Titre ........................................................................................................ i Composition du Jury ................................................................................... .ii Résumé .................................................................................................. .iii Abstract. ................................................................................................. iv Table des matières ....................................................................................... v Liste des tableaux ...................................................................................... viii Liste des figures ............... '" .................. '" ................................................... .ix Liste des abréviations ...................................................................................... x Dédicace ................................................................................................. xii Remerciements ......................................................................................... xiii 1.0 Introduction ............................................................................. , ......... 1 1.1 Histoire de la dépression .................................................................. .2 ] .2 Épidémiologie ............................................................................... 3 1.3 Coûts de la dépression .................................................................. A lA Classification de la dépression ............................................................ 5 1A.1 Définition du DSM-IV ..................................... 5 1A.2 Typologie de la dépression ................................ 6 1.4.3 . Facteur anxieux dans la dépression ....................... 7 1.5 Neurobiologie de la dépression ................... , .............................. 9 v 1.5.1 Anomalies structurales et fonctionnelles ............... ] 0 1.5.2 La sérotonine .................................................. ] 2 1.5.3 Noradrénaline ............................................... ] 5 1.5.4 Dopamine ................................................... 16 1.5.5 Axe hypothalamo-corticosurrénalien ....................... 17 ] .5.6 Facteurs neurotrophiques ................................ .22 1.6 Traitement de la dépression ..................................................... 23 1.6.1 Antidépresseurs ............................................... .23 1.6.2 Classification des antidépresseurs ...................... .24 1.6.3 Mécanismes d'action des antidépresseurs ............. 29 1.7 Buspirone ...................................................................... 38 1.7.1 Indication pour l'anxiété généralisée ................... 38 ] .7.2 Mécanisme d'action .......................................... 39 ].8 La dépression résistante ..................................................... .4] 1.9 Objectifs des études faisant partie du mémoire .......................... .44 2.0 L'efficacité de la buspirone dans la dépression anxieuse ................................ .46 Introduction ...........................................................................47 Population et méthodes .............................................................. .48 Résultats ................................................................................ 51 Discussion ............................................................................. 57 VI 3.0 Quetiapine augmentation of treatment resistant depression: a comparison with lithium ........................................................................................... 60 Introduction ............................................................................... 70 Population et méthodes (patients and methods) .................................... 73 Résultats (results) ....................................................................... 76 4.0 Discussion ....................................................................................... 92 5.0 Bibliographie .................................................................................... 94 VII Liste des ta blea ux Tableau 1. Caractéristiques démographiques ................................................ .48 Tableau II. Résumé des résultats propres à l'échelle de dépression de Hamilton ...............' .............................................................................. 50 Tableau III. Résumé des résultats propres à l'échelle d'anxiété de Hamilton ............................................................................................ ,.. 51 Tableau IV. Résumé des résultats propres à l'échelle Échelle de Derogatis) ............... '.'............................................................................. 52 Tableau V. Impression Clinique Globale ........................................................
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