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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: 3.1). 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, Aug 17, 2015
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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 · 2.81 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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    ABSTRACT: Post-hoc pooled analysis of data from two 6-month randomised controlled trials in patients with major depressive disorder (MDD) revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. Escitalopram (n=394) produced a significantly (p<0.01) greater mean treatment difference of 2.0 points in primary endpoints, judged using the Montgomery-Asberg Depression Rating Scale (MADRS) total score, compared with paroxetine (n=383). Significant differences were also observed in Clinical Global Impression (CGI)--severity (escitalopram, 2.1; paroxetine, 2.4; p<0.01) and CGI--improvement (escitalopram, 1.8; paroxetine, 2.0: p<0.01). In the sub-group of severely depressed patients (baseline MADRS> or = 30), escitalopram showed further improved efficacy compared with paroxetine in all scores. This analysis supports previous observations of superior efficacy and tolerability of long-term escitalopram treatment (10 to 20 mg/day) compared with paroxetine (20 to 40 mg/day). Escitalopram is a good therapeutic option for the long-term treatment of MDD, particularly in severely depressed patients.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2009; 19(4):229-37. DOI:10.1016/j.euroneuro.2008.12.003 · 5.40 Impact Factor
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    • "For the MADRS, remission was defined as a MADRS scorer12, and response was defined by at least a 50% decrease from baseline [Burke et al., 2002; Lepola et al., 2003]. Adverse events were assessed with a locally developed Adverse Event Record form based on the literature [Bielski et al., 2004; Burke et al., 2002; Colonna et al., 2002; Lepola et al., 2003; Montgomery et al., 2004; Wade et al., 2002]. The severity of adverse events was rated by the investigator as mild (patient aware of a symptom, but easily tolerated), moderate (discomfort enough to interfere with usual activity), or severe (incapacitating, with inability to work or perform routine activities). "
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    ABSTRACT: Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."
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