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


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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    • "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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    Neuropsychiatric Disease and Treatment 02/2011; 7(1):39-49. DOI:10.2147/NDT.S12531 · 1.74 Impact Factor
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    • "Escitalopram, an allosteric serotonin reuptake inhibitor (ASRI) (Sanchez, 2006), is the therapeutically active S-stereoisomer of racemic citalopram and is significantly more effective than citalopram, which also includes the R-stereoisomer (Colonna et al., 2005; Lepola et al., 2004; Moore et al., 2005). Paroxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant. "
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    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2009; 19(4):229-37. DOI:10.1016/j.euroneuro.2008.12.003 · 4.37 Impact Factor
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