La prise en charge thérapeutique des patients atteints de dépression sévère reste encore un challenge pour les médecins. Par rapport à la forme légère ou modérée, la dépression sévère se caractérise souvent par une durée plus longue, une co-morbidité supérieure, une plus faible probabilité de rémission spontanée et un taux de rechute plus important. Par ailleurs, si l'efficacité des nouveaux antidépresseurs est bien établie dans la dépression légère à modérée, beaucoup moins d'études ont été réalisées dans la dépression sévère. Probablement parce que la dépression sévère n'est pas perçue comme une entité à part, mais comme un continuum dans la clinique de cette pathologie, et aussi peut-être en raison d'une absence de consensus clair sur la définition même de cette sévérité. Après avoir utilisé les définitions basées sur la clinique et sur le mode de prise en charge, les auteurs semblent désormais privilégier l'utilisation des échelles cliniques avec un seuil spécifique pour cette définition. En utilisant l'échelle MADRS (Montgomery-Åsberg Depression Rating Scale) et la valeur seuil de 30 pour définir la sévérité de la dépression, nous avons réalisé une analyse poolée avec les données des trois essais cliniques comparant l'efficacité du escitalopram à celle du citalopram. Les résultats montrent de façon constante une meilleure efficacité du escitalopram par rapport au citalopram, dans cette indication particulière qu'est la dépression sévère.

Background - Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression. Objective - To determine if escitalopram is more effective than citalopram in patients with severe depression. Methods - Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50 % reduction in baseline MADRS total score or by at least a 60 % reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score ≤ 12. Results - Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p = 0.003). This significant difference was observed as early as week 1 (p = 0.01). Response rates were significantly higher for escitalopram than for citalopram (56 % vs 41 % respectively, p = 0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43 % vs 33 % respectively, p = 0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results. Discussion - This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.