Escitalopram in the treatment of major depressive disorder: a meta-analysis.
OBJECTIVE
To assess the relative antidepressant efficacy of escitalopram and comparator antidepressants.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kennedy
Sidney H
SH
University of Toronto, Toronto, Ontario, Canada. sidney.kennedy@uhn.on.ca
Andersen
Henning F
HF
Thase
Michael E
ME
D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors