Baseline severity of depression predicts antidepressant drug response relative to escitalopram

Abstract

Objective: The intent of this pooled analysis was to determine the relationship between baseline depression symptom severity and treatment response for escitalopram compared to that for other pooled antidepressant medications (citalopram, duloxetine, fluoxetine, paroxetine, sertraline and venlafaxine). Methods: Data were pooled from controlled clinical trials comparing escitalopram with other antidepressants for the treatment of major depression. The 15 trials meeting the inclusion criteria comprised 2,216 patients treated with escitalopram and 2,085 treated with one of the other antidepressants. The primary outcome measure of change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was analyzed by an analysis of covariance, using the method of last-observation-carried-forward for missing values and adjusting for baseline and center values. Results: There was a significant interaction between baseline MADRS total score and treatment group (p = 0.0208). Response to escitalopram was stable regardless of baseline severity. For the pooled active comparators, response decreased with increasing baseline symptom severity. This differential efficacy of escitalopram with increasing symptom severity was confirmed by the analyses of the pooled 24-item Hamilton Depression Rating Scale (HAMD-24) results. A HAMD-24 single item analysis indicated that the sum of the baseline psychomotor retardation and hopelessness item scores significantly predicted which patients would benefit from treatment with escitalopram versus a comparator. Conclusion: Newer generation antidepressant medications clearly differ in their efficacy as a function of baseline symptom severity. The selective serotonin reuptake inhibitor escitalopram had superior efficacy in the treatment of more severe depression, perhaps attributable to differential efficacy related to symptoms of negativistic thinking.

Keywords::

• escitalopram
• item analysis
• meta-analysis
• severe depression

Acknowledgments

The authors acknowledge Ian Ford at the Robertson Centre for Biostatistics, University of Glasgow, for providing consultation on the methods of statistical data analysis. We thank CB Nemeroff for intellectual input to the manuscript, and DJ Simpson for assistance in the preparation of the manuscript. HF Andersen was responsible for the statistical analyses. Each author contributed to the conception of the pooled analysis, interpretation of the data analysis, drafting and revising the article and final approval of the version that was published.

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