Escitalopram in the treatment of major depressive disorder: A meta-analysis

ABSTRACT

Objective: To assess the relative antidepressant efficacy of escitalopram and comparator antidepressants.

Research design and 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.

Main outcome measures: The primary outcome measure was the treatment difference in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 8. Secondary outcome measures were response and remission (MADRS total score ≤ 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 ≥ 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.

Key words: :

• Escitalopram
• Major depressive disorder
• Meta-analysis
• Selective serotonin reuptake inhibitors
• Serotonin norepinephrine reuptake inhibitors

Acknowledgments

Declaration of interest: This study was funded by H. Lundbeck A/S. S. H. K. has received grant funding and consulting honoraria from Lundbeck and has also received grant funding or consulting honoraria within the past 5 years from Advanced Neuromodulation Systems, AstraZeneca, Biovail, Boehringer-Ingelheim, Brain Cells Inc., Eli Lilly & Co, GlaxoSmithKline, Janssen-Ortho, Merck-Frosst, Organon, Pfizer, Servier, and Wyeth. M. E. T. has received consultancy honoraria from Lundbeck and Forest Pharmaceuticals within the past 5 years. During this time frame, M. E. T. has also been an advisor/consultant for AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Inc., Cyberonics, Inc., Eli Lilly & Co., GlaxoSmithKline, Janssen Pharmaceutica, MedAvante, Inc., Neuronetics, Inc., Novartis, Organon Inc., Pfizer, Inc., Sanofi Aventis, Sepracor, Inc., Shire US, Inc., Transcept, and Wyeth Pharmacueticals; has been a member of the Speakers’ Bureaus for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlazoSmithKline, and Wyeth Pharmacueticals. He has also received research grants from the National Institute of Mental Health, Eli Lilly, Sepracor, and GlaxoSmithKline. He has equity holdings in MedAvante, Inc., and has received income from royalties from American Psychiatric Publishing, Inc., Guilford Publications and Herald House. H. F. A., a statistician, is a former employee of Lundbeck and has bonds in Lundbeck. The authors thank Eli Lilly& Co for providing unpublished results from the duloxetine study by Nierenberg and colleagues41. The authors gratefully acknowledge the technical assistance of DJ Simpson (Lundbeck) during the preparation of the manuscript.