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.
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- "The differences in effi cacy appeared more clear-cut in severely depressed patients (Kennedy et al. 2009; Ali and Lam 2011). When compared to venlafaxine or duloxetine (alone or pooled), escitalopram was found to be likewise more effective and better tolerated in MDD treatment (Montgomery and Andersen 2006; Kennedy et al. 2009; Kornstein et al. 2009). In a specifi c study, escitalopram was found to more likely result in remission without concurrent side effects in comparison with SNRIs (Signorovitch et al. 2011). "
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ABSTRACT: Objectives. Only few studies investigated treatment strategies for treatment resistant depression (TRD). The objective of this multicentre study was to evaluate TRD patients who did not respond to at least two antidepressants. Methods. A total of 417 patients, who failed to respond to a previous retrospectively assessed antidepressant (AD1), were firstly included in a 6-week venlafaxine treatment (AD2); secondly, those who failed to respond were treated for further 6 weeks with escitalopram (AD3). Results. Out of 417 patients who had failed to respond to previous treatment (AD1), 334 completed treatment with venlafaxine to prospectively define TRD. In the intent to treat (ITT) population in the first phase of the trial (AD2), responders to venlafaxine were 151 (36.21%) out of which remitters were 83 (19.90%). After phase one, 170 non-responders, defined as TRD, were included in the second phase and 157 completed the course. Of the 170 ITT entering the second phase (AD3), responders to escitalopram were 71 (41.76%) out of which remitters were 39 (22.94%). After the third treatment, patients showed a dropout rate of 7.65% and a rate of presence of at least one serious adverse event of 19.18%. Conclusions. Relevant rates of response and remission may be observed after a third line treatment in patients resistant to two previous treatments. A relevant limitation of this study was represented by the design: naturalistic, non-randomized, open-label, without a control sample and with unblinded raters.
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.
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