Efficacy of escitalopram in patients with severe depression: A pooled analysis

Centre Medico-Psychologique B, Centre Hospitalier Universitaire, Clermont-Ferrand, France.
International Journal of Clinical Practice (Impact Factor: 2.57). 04/2005; 59(3):268-75. DOI: 10.1111/j.1742-1241.2005.00440.x
Source: PubMed


Escitalopram is an effective, well-tolerated treatment for major depressive disorder in both primary and specialist settings. This analysis compared the efficacy of escitalopram with citalopram in the treatment of patients with severe depression [defined as a score of > or =30 Montgomery-Asberg Depression Rating Scale (MADRS)]. Data from three clinical trials were used for this pooled analysis. A total of 506 severely depressed patients were included (169 received escitalopram, 171 citalopram and 166 placebo). Mean change from baseline in MADRS total scores (primary efficacy parameter) was significantly higher in the escitalopram-treated group compared with the citalopram-treated group (p = 0.003). There was a significant difference in response between escitalopram and citalopram (56 vs. 41%, respectively, p = 0.007). Results from secondary efficacy parameters (Hamilton rating for depression and Clinical Global Impression of Improvement and Severity scales) were consistent with previous results. The benefits in severe depression of escitalopram vs. citalopram were so demonstrated.

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Available from: P.-M. Llorca, Mar 28, 2014
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    • "In addition , it appears to have allosteric modulatory capability at the serotonin transporter, whereby the binding of one escitalopram molecule to the transporter is enhanced by the binding of a second molecule at an allosteric modulatory site (Chen et al., 2005; Sanchez and Kreilgaard, 2004). Escitalopram has demonstrated efficacy in the treatment of major depressive disorder (Einarson, 2004; Llorca et al., 2005; Moore et al., 2005), and its metabolite N-desmethylescitalopram has also been shown to be active (Tatsumi et al., 1997). CYP2C19 is involved in the metabolism of escitalopram , producing its primary metabolite N-desmethylescitalopram (Herrlin et al., 2003; Sindrup et al., 1993; "
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    ABSTRACT: In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.
    Journal of Psychopharmacology 09/2011; 26(3):398-407. DOI:10.1177/0269881111414451 · 3.59 Impact Factor
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    • "Escitalopram has been shown to be superior to paroxetine (Boulenger et al. 2006 ; Kasper et al. 2009) in a prospective double-blind study and in meta-analyses of randomized controlled trials (RCTs) comparing escitalopram to commonly prescribed antidepressants (Kennedy et al. 2006, 2009). The superiority of escitalopram is even more clear-cut in severe depression, as shown in individual studies in which it was compared to citalopram (the racemic mixture of escitalopram and the R-enantiomer), paroxetine, and venlafaxine (Boulenger et al. 2006 ; Montgomery & Andersen, 2006 ; Moore et al. 2005) and is seen in several meta-analyses (Auquier et al. 2003 ; Lam & Andersen, 2006 ; Kennedy et al. 2006, 2009 ; Lepola et al. 2004 ; Llorca et al. 2005). The study of Moore et al. (2005) was designed to test prospectively for a possible difference between 20 mg escitalopram and 40 mg citalopram in patients with severe depression [Montgomery–Asberg Depression Rating Scale (MADRS ; Montgomery & A ˚ sberg, 1979) score of o30], and the observed difference of 2.1 was significant and clinically relevant. "
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    ABSTRACT: The aim of this review was to assess the clinical relevance of the relative antidepressant efficacy of escitalopram and citalopram by meta-analysis. Studies in major depressive disorder (MDD) with both escitalopram and citalopram treatment arms were identified. Adult patients had to meet DSM-IV criteria for MDD. The primary outcome measure was the treatment difference in Montgomery-Asberg Depression Rating Scale (MADRS) total score at week 8 (or last assessment if <8 wk). Secondary outcome measures were response (≥ 50% improvement from baseline) and remission (MADRS ≤ 12). A search of the literature and websites found eight randomized controlled trials (RCTs) and onr naturalistic trial, with a total of 2009 patients (escitalopram, n=995; citalopram, n=1014). Escitalopram was significantly more effective than citalopram in overall treatment effect, with an estimated mean treatment difference of 1.7 points at week 8 (or last assessment if <8 wk) on the MADRS (95% CI 0.8-2.6, p=0.0002) (six RCTs used the MADRS), and in responder rate (8.3 percentage points, 95% CI 4.4-12.3) (eight RCTs) and remitter rate (17.6 percentage points, 95% CI 12.1-23.1) analyses (reported for four RCTs), corresponding to number-needed-to-treat (NNT) values of 11.9 (p<0.0001) for response and 5.7 (p<0.0001) for remission. The overall odds ratios were 1.44 (p<0.0003) for response and 1.86 (p<0.0001) for remission, in favour of escitalopram. In this meta-analysis, the statistically significant superior efficacy of escitalopram compared to citalopram was shown to be clinically relevant.
    The International Journal of Neuropsychopharmacology 03/2011; 14(2):261-8. DOI:10.1017/S146114571000115X · 4.01 Impact Factor
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    • "The long-term efficacy of escitalopram, in terms of improved symptom severity, has been demonstrated in a number of six-or 12-month open-label studies (Anders et al., 2008; Kasper et al., 2006a; Wade et al., 2006), in which the majority of patients (72% to 86%) achieved remission (MADRS 12). It would, therefore, appear that the mechanistic advantages of escitalopram over citalopram, in terms of increased potency (Hyttel et al., 1992) and its known effect on the SERT through an affinity-modulating allosteric site (Chen et al., 2005), translate into clinical benefits in patients with MDD, as demonstrated in the pooled analysis by Llorca et al. (2005), which showed significantly greater mean change from baseline in MADRS with escitalopram versus citalopram (56% vs 41%, respectively; p ¼ 0.007). "
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    ABSTRACT: The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents.
    Journal of Psychopharmacology 02/2010; 24(8):1143-52. DOI:10.1177/0269881109349835 · 3.59 Impact Factor
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