Lepola U, Wade A, Andersen HF. Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of 2 positive placebo-controlled studies in major depressive disorder

University of Helsinki, Helsinki, Uusimaa, Finland
International Clinical Psychopharmacology (Impact Factor: 2.46). 05/2004; 19(3):149-55. DOI: 10.1097/00004850-200405000-00005
Source: PubMed

ABSTRACT Escitalopram is the S-enantiomer of citalopram. In this study, we compared the efficacy of equivalent dosages of escitalopram and citalopram in the treatment of moderate to severe major depressive disorder (MDD), based on data from two, pooled, randomized, double-blind, placebo-controlled studies of escitalopram in which citalopram was the active reference. The primary efficacy parameter was the mean change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score. Significant differences in favour of escitalopram were observed for the MADRS [P<0.05, observed cases (OC)/last observation carried forward (LOCF)] and Clinical Global Improvement-Severity of Illness scores (CGI-S; P<0.05, OC/LOCF). Escitalopram separated from placebo at week 1 on the primary efficacy parameter, whereas citalopram first separated from placebo at week 6. An analysis of time to response showed that escitalopram-treated patients responded significantly faster to treatment than citalopram-treated patients (P<0.01). More patients responded to and achieved remission with escitalopram than to citalopram (P<0.05, OC). The HAMD scale was only used in the fixed-dose study, where escitalopram-treated patients had a significant reduction in HAMD-17 total score at week 8 compared to citalopram-treated patients (P<0.05, OC/LOCF). In the pooled subpopulation of severely ill patients (MADRS> or = 30), escitalopram-treated patients showed greater improvement than citalopram-treated patients (P<0.05, LOCF/OC). Escitalopram showed consistently superior efficacy compared to citalopram in the treatment of moderate to severe MDD on all efficacy parameters, and was similarly well tolerated.

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Available from: Alan G Wade, Sep 27, 2015
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    • "For escitalopram, it takes 2 weeks before 5-HT neuronal firing returns to control levels in rats, but for most SSRIs, it takes at least 3 weeks, suggesting a faster onset of action for escitalopram, possibly due to its action at the allosteric site (El Mansari et al., 2005; Mnie-Filali et al., 2007). This is consistent with the indication of escitalopram having a faster clinical onset than other SSRIs (Lepola et al., 2004; Kasper et al., 2006; Wade and Andersen, 2006). Among other neurochemical changes during antidepressant treatment, the neurotropin brain-derived neurotrophic factor (BDNF) was recently reviewed (Zhong et al., 2012a). "
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    ABSTRACT: It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.
    International clinical psychopharmacology 01/2014; 29(4). DOI:10.1097/YIC.0000000000000023 · 2.46 Impact Factor
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    • "Of the 18 pooled analysis studies, we excluded five studies18–22 primarily focusing on topics (symptom clusters, onset of action, predictors of response) other than efficacy, two studies17,23 which were considered subsets of subsequent larger pooled studies, and five studies24–28 focusing on severity analyses only. This left six pooled analysis studies for review (Table 1). "
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    ABSTRACT: Escitalopram is an allosteric selective serotonin reuptake inhibitor (SSRI) with some indication of superior efficacy in the treatment of major depressive disorder. In this systematic review, we critically evaluate the evidence for comparative efficacy and tolerability of escitalopram, focusing on pooled and meta-analysis studies. A literature search was conducted for escitalopram studies that quantitatively synthesized data from comparative randomized controlled trials in MDD. Studies were excluded if they did not focus on efficacy, involved primarily subgroups of patients, or synthesized data included in subsequent studies. Outcomes extracted from the included studies were weighted mean difference or standard mean difference, response and remission rates, and withdrawal rate owing to adverse events. The search initially identified 24 eligible studies, of which 12 (six pooled analysis and six meta-analysis studies) met the criteria for review. The pooled and meta-analysis studies with citalopram showed significant but modest differences in favor of escitalopram, with weighted mean differences ranging from 1.13 to 1.73 points on the Montgomery Asberg Depression Rating Scale, response rate differences of 7.0%-8.3%, and remission rate differences of 5.1%-17.6%. Pooled analysis studies showed efficacy differences compared with duloxetine and with serotonin noradrenaline reuptake inhibitors combined, but meta-analysis studies did not. The effect sizes of the efficacy differences increased in the severely depressed patient subgroups. Based on pooled and meta-analysis studies, escitalopram demonstrates superior efficacy compared with citalopram and with SSRIs combined. Escitalopram shows similar efficacy to serotonin noradrenaline reuptake inhibitors but the number of trials in these comparisons is limited. Efficacy differences are modest but clinically relevant, especially in more severely depressed patients.
    Neuropsychiatric Disease and Treatment 02/2011; 7(1):39-49. DOI:10.2147/NDT.S12531 · 1.74 Impact Factor
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    • "The evaluation of the efficacy of escitalopram in comparison with the SNRIs venlafaxine XR and duloxetine may have been limited by the small number of studies directly comparing these agents; however, these studies were performed in a large number of patients (>1500 patients) and, thus, were sufficiently powered to identify important clinical differences between the treatments (Cipriani et al., 2009). Summary points for efficacy: (i) efficacy advantage for escitalopram versus citalopram has been demonstrated in five randomized studies (Burke et al., 2002; Colonna et al., 2005; Lepola et al., 2003; Moore et al., 2005; Yevtushenko et al., 2007) and two pooled analyses of clinical trials (Gorman et al., 2002; Lepola et al., 2004); (ii) escitalopram may have an efficacy advantage over paroxetine , in terms of significant improvements in MADRS, HAM-D and CGI-S scores and fewer discontinuations owing to lack of efficacy (Baldwin et al., 2006; Boulenger et al., 2006); (iii) the efficacy of escitalopram compared with fluoxetine (Mao et al., 2008; Kasper et al., 2005) and sertraline (Ventura et al., 2007) requires further evaluation; (iv) escitalopram and sertraline might be the best choice of antidepressant when starting treatment of patients with moderate to severe MDD (Cipriani et al., 2009); (v) the SNRI venlafaxine XR may be associated with greater remission or response rates in patients with MDD compared with SSRIs (Papakostas et al., 2007; Smith et al., 2002; Nemeroff et al., 2008; Thase, 2008 Thase et al., 2005; Burk et al., 2002); (vi) escitalopram has comparable efficacy to venlafaxine XR, with a possible slight advantage for escitalopram in patients with severe MDD (Bielski et al., 2004; Montgomery et al., 2004) Regarding safety and tolerability, escitalopram offers tolerability advantages over duloxetine, paroxetine and venlafaxine XR (see summary points below) and may be preferable to those antidepressants in some patients with MDD. Summary points for safety: (i) superior tolerability for escitalopram versus duloxetine, particularly for nausea, insomnia, dizziness and vomiting has been demonstrated in three randomized studies (Khan et al., 2007; Nierenberg et al., 2009; Wade et al., 2007) and a pooled analysis of two clinical trials (Lam et al., 2008) (ii) escitalopram offers tolerability advantages over paroxetine (Baldwin et al., 2006; Boulenger et al., 2006) and venlafaxine XR (Bielski et al., 2004; Montgomery et al., 2004, 2006); (iii) escitalopram is less likely to cause discontinuation symptoms than several other antidepressants (Baldwin et al., 2006; Bielski et al., 2004; Boulenger et al., 2006; Kasper et al., 2005; Khan et al., 2007; Montgomery et al., 2004, 2006; Taylor et al., 2006a; Wade et al., 2007); (iv) no evidence of emergent risk of suicide with escitalopram (Baldwin et al., 2007; Pedersen, 2005); (v) incidence of sexual dysfunction-related adverse events similar to citalopram, but lower than venlafaxine XR and paroxetine (Baldwin et al., 2007). "
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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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