Einarson TR. Evidence based review of escitalopram in treating major depressive disorder in primary care. Int Clin Psychopharmacol 19: 305-310

Faculty of Pharmacy, Department of Clinical Pharmacology, University of Toronto, Toronto, Ontario, Canada.
International Clinical Psychopharmacology (Impact Factor: 2.46). 10/2004; 19(5):305-10. DOI: 10.1097/01.yic.0000139342.22133.77
Source: PubMed


The study aimed to summarize clinical data for escitalopram in the treatment of major depressive disorder in primary care. Medline, Embase and Cochrane databases were searched for randomized controlled trials of escitalopram (10-20 mg/day for 8 weeks) versus other antidepressants in therapeutic doses or placebo. Patients were required to have had moderate/severe depression, with Montgomery-Asberg Depression Rating Scale (MADRS) scores recorded at baseline and 8 weeks. Outcomes examined were remission rates (MADRS</=12) and response rates (>/=50% decrease from baseline in MADRS at week 8). Data were combined using a random effects meta-analytic model. Of the 15 studies identified, 11 were rejected (five not primary care, four duplicate reports, one lacked 8-week MADRS scores, one not depression) and four were accepted (n=1472 patients). The four studies had nine arms, four for escitalopram (n=654), two for citalopram (n=333), one for venlafaxine-XR (n=142) and two for placebo (n=343). Remission rates for escitalopram were superior to placebo (48.7% versus 37.6%, P=0.003) and citalopram (52.8% versus 43.5%, P=0.003) but similar to venlafaxine-XR (P=0.97). Response rates were superior to placebo (48.7% versus 43.1%, P<0.001) and citalopram (62.5% versus 49.5%, P=0.001) but not venlafaxine-XR (P=0.52). Adverse events were comparable among active drugs (P<0.05). Remission rates for escitalopram were superior to placebo (48.7% versus 37.6%, P=0.003) and citalopram (52.8% versus 43.5%, P=0.003) but similar to venlafaxine-XR (P=0.97). Response rates were superior to placebo (48.7% versus 43.1%, P<0.001) and citalopram (62.5% versus 49.5%, P=0.001) but not venlafaxine-XR (P=0.52). Adverse events were comparable among active drugs (P>0.05). Remission and response rates of escitalopram in primary care are clinically superior to placebo and citalopram, but similar to venlafaxine-XR. Further head-to-head trials are warranted to verify these findings. A pharmacoeconomic analysis is also required to determine whether these clinical advantages for the patients translate into economic advantages for the health care system.

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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.
    Full-text · Article · Sep 2011 · Journal of Psychopharmacology
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    • "Interestingly, the CGI-S scores also revealed that escitalopram was associated with a faster onset of action than other antidepressants. An earlier meta-analysis confirmed the superiority of escitalopram versus citalopram with respect to both response and remission rates, but found no difference between escitalopram and venlafaxine XR (Einarson, 2004). This is perhaps not surprising given the small number of patients who received venlafaxine XR in the single study included in this analysis. "
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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.
    Full-text · Article · Feb 2010 · Journal of Psychopharmacology
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    • "Our data suggest that the observed treatment refraction is not caused by subdosing the antidepressant, but rather indicating that an unidentified pathological dose-independent mechanism is involved. The fraction of responders to escitalopram treatment in the CMS model closely mirrors the observed clinical efficacies (Einarson, 2004; Bondolfi et al, 1996). The CMS model has been optimized and repeatedly run in our laboratory. "
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    ABSTRACT: From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression. To study a potential correlation between recovery and hippocampal cytogenesis, we established the chronic mild stress (CMS) rat model of depression. When rats are subjected to CMS, several depressive symptoms develop, including the major symptom anhedonia. Rats were exposed to stress for 2 weeks and subsequently to stress in combination with antidepressant treatment for 4 consecutive weeks. The behavioral deficit measured in anhedonic animals is a reduced intake of a sucrose solution. Prior to perfusion animals were injected with bromodeoxyuridine (BrdU), a marker of proliferating cells. Brains were sectioned horizontally and newborn cells positive for BrdU were counted in the dentate gyrus and tracked in a dorsoventral direction.CMS significantly decreased sucrose consumption and cytogenesis in the ventral part of the hippocampal formation. During exposure to the antidepressant escitalopram, given as intraperitoneally dosages of either 5 or 10 mg/kg/day, animals distributed in a bimodal fashion into a group, which recovered (increase in sucrose consumption), and a subgroup, which refracted treatment (no increase in sucrose consumption). Chronic treatment with escitalopram reversed the CMS-induced decrease in cytogenesis in the dentate gyrus of the ventral hippocampal formation, but in recovered animals only. Our data show a correlation between recovery from anhedonia, as measured by cessation of behavioral deficits in the CMS model, and an increase in cytogenesis in the dentate gyrus of the ventral hippocampal formation.
    Full-text · Article · Dec 2006 · Neuropsychopharmacology
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