Escitalopram in the treatment of major depressive disorder: A meta-analysis
To assess the relative antidepressant efficacy of escitalopram and comparator antidepressants.
A meta-analysis was performed using studies in major depressive disorder (MDD) comparing escitalopram with active controls, including selective serotonin reuptake inhibitors [SSRIs] (citalopram, fluoxetine, paroxetine, sertraline) and serotonin/noradrenaline reuptake inhibitors [SNRIs] (venlafaxine, duloxetine). 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. Secondary outcome measures were response and remission (MADRS total score < or = 12) rates.
Individual patient data (N = 4549) from 16 randomized controlled trials were included in the analyses (escitalopram n = 2272, SSRIs n = 1750, SNRIs n = 527). Escitalopram was significantly more effective than comparators in overall treatment effect, with an estimated mean treatment difference of 1.1 points on the MADRS (p < 0.0001), and in responder (63.7 vs. 58.3%, p < 0.0001) and remitter (53.1 vs. 49.4%, p < 0.0059) analyses. Escitalopram was significantly superior to SSRIs, with an estimated difference in response of 62.1 vs. 58.4% and remission of 51.6 vs. 49.0%. In comparison to SNRIs, the estimated difference in response was 68.3 vs. 59.0% (p = 0.0007) and for remission the difference was 57.8 vs. 50.5% (p = 0.0088). These results were similar for severely depressed patients (baseline MADRS > or = 30). Sensitivity analyses were performed with data from articles reporting Hamilton Rating Scale for Depression (HAMD) scores. The 8-week withdrawal rate due to adverse events was 5.4% for escitalopram and 7.9% for the comparators (p < 0.01). This difference was accounted for by statistically significant higher attrition rates in the SNRI comparisons. This work may be limited by the clinical methodology underlying meta-analytic studies, in particular, the exclusion of trials that fail to meet predetermined criteria for inclusion.
In this meta-analysis, superior efficacy of escitalopram compared to SSRIs and SNRIs was confirmed, although the superiority over SSRIs was largely explained by differences between escitalopram and citalopram.
Available from: Angelos Halaris
- "A metaanalysis comparing ESC and citalopram supported the results of the controlled studies (Montgomery et al., 2011). In addition, ESC has a more favorable side effect profile compared to other SSRIs or SNRIs (Kennedy et al., 2009). It is generally well tolerated as maintenance treatment and, compared to other SSRIs and SNRIs, ESC has the highest matched acceptability and efficacy rate (Kirino, 2012), although weight gain and sexual dysfunction can be limiting side effects with this agent as well. "
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ABSTRACT: A pro-inflammatory state and a dysregulation in the tryptophan/kynurenine pathway have been documented in depression. This study examined whether treatment with the SSRI, escitalopram (ESC), could suppress inflammation and favorably shift metabolites of the kynurenine pathway in patients with major depressive disorder (MDD) within the utilized treatment period. Twenty seven healthy control subjects were included for comparison. Thirty patients were enrolled after completing baseline assessments. They received a 12-week ESC monotherapy. Twenty subjects were completers. Clinical assessments were carried out at each visit using the HAM-D, HAM-A, CGI and BDI rating scales. Blood samples were collected at each assessment and stored until analyzed. Cytokines were analyzed with Randox multiplex assay and tryptophan and kynurenine metabolites were analyzed using HPLC/GCMS. Baseline plasma concentrations of hsCRP, TNFα, IL6 and MCP-1 were significantly higher in patients compared to healthy controls. IL10 trended toward an increase. Baseline plasma IL1β correlated significantly with IL1α, and IL4. Patients showed significant improvement in all outcome measures with a high remission rate. Significant correlations were obtained between specific symptoms and certain biomarkers at baseline but these correlations must be viewed as very preliminary. During ESC treatment concentrations of inflammatory biomarkers did not change except for TNFα that trended lower. Metabolites and ratios of the tryptophan/kynurenine pathway showed reductions of the neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, 3-hydroxykynurenine/kynurenine, quinolinic acid/tryptophan, kynurenic acid/quinolinic acid and quinolinic acid/3-hydroxykynurenine. The results indicate that ESC may exert its antidepressant effect in part through inhibition of synthesis of certain neurotoxic kynurenine metabolites and possibly also through reduction of the inflammatory response, although there was no concordance in the time course of changes between antidepressant efficacy and reversal of the pro-inflammatory status.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Journal of Psychiatric Research 05/2015; 66-67. DOI:10.1016/j.jpsychires.2015.04.026 · 3.96 Impact Factor
Available from: sciencedirect.com
- "For this post-hoc analysis, patients were stratified at the beginning of Phase C into 3 groups: mild (Montgomery–Åsberg Depression Rating Scale [MADRS] total score r 24), moderate (MADRS total score 25–30), and severe (MADRS total score Z31). A MADRS total score of Z31 was previously found to best distinguish moderate and severe depression (Muller et al., 2003), and a cutoff of Z30 has been used in several prior studies (Bose et al., 2012; Kennedy et al., 2009; Papakostas et al., 2012). However, the definition of mild versus moderate depression using the MADRS is not well established; therefore, definitions for mild and moderate depression in the current study were adapted from previous research (Kearns et al., 1982). "
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ABSTRACT: There is a paucity of evidence for outcome predictors in patients with major depressive disorder (MDD) not responding to initial antidepressant therapy (ADT). This post-hoc analysis evaluated whether MDD severity affects response to adjunctive aripiprazole.
Data from 3 randomized, double-blind, placebo-controlled trials of adjunctive aripiprazole in adults with MDD and inadequate response to 1 to 3 ADT trials were pooled and stratified based on Montgomery-Åsberg Depression Rating Scale (MADRS) total score (mild, ≤24; moderate, 25-30; severe, ≥31). Treatment differences in change in MADRS total score and rates of response (≥50% MADRS improvement) and remission (response with MADRS total score ≤10) were analyzed at endpoint. Adverse events were assessed within each subgroup.
Aripiprazole produced greater improvement than placebo in the MADRS total score regardless of MDD severity at baseline (between-treatment difference [95% CI]: mild, -2.5 [-4.0 to -1.1]; moderate, -3.2 [-4.9 to -1.6]; severe, -4.5 [-6.8 to -2.2]). Compared with placebo, adjunctive aripiprazole increased the likelihood of response in all subgroups (risk ratio [95% CI]: mild, 1.50 [1.15, 1.95]; moderate, 1.51 [1.09, 2.11]; severe, 1.95 [1.23, 3.10]). Common treatment-emergent adverse events included akathisia and restlessness.
The original studies were not designed to assess the efficacy of adjunctive aripiprazole by baseline severity, and this post-hoc analysis was not powered to evaluate differences in severity subgroups.
In patients who failed to respond to initial ADT, adjunctive aripiprazole was more effective than placebo in mild, moderate, and severe MDD strata.
ClinicalTrial.gov: NCT00095823, NCT00105196, and NCT00095758.
Journal of Affective Disorders 06/2014; 162:20-5. DOI:10.1016/j.jad.2014.03.017 · 3.38 Impact Factor
Available from: Connie Sánchez
- "Based on an analysis of 10 studies involving a total of 2687 MDD patients up to 2004, escitalopram was found to have significantly higher overall treatment effect (estimated difference in treatment effect of 1.07 points), response rate (odds ratio 1.29), and remission rate (odds ratio 1.21) compared with all comparators including paroxetine and sertraline (Kennedy et al., 2006). In a follow-up meta-analysis comparing escitalopram with active controls including SSRIs (citalopram, fluoxetine, paroxetine, sertraline) and SNRIs (venlafaxine, duloxetine) involving 4549 patients in 16 randomized controlled trials, escitalopram was again found to be significantly more effective than comparators in treatment effect (measured as change from baseline in MADRS total score), as well as in the rates of response and remission (Kennedy et al., 2009). The results suggest the overall superior efficacy of escitalopram compared with paroxetine and sertraline as well as other SSRIs and SNRIs, though the superiority to other SSRIs was to the largest degree between escitalopram and citalopram (Kennedy et al., 2009), a difference that has been well established (Montgomery et al., 2011). "
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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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