Fixed-Dose Trial of the Single Isomer SSRI Escitalopram in Depressed Outpatients

Background: Escitalopram is the single isomer responsible for the serotonin reuptake inhibition produced by the racemic antidepressant citalopram. The present randomized, double-blind, placebo-controlled, fixed-dose multicenter trial was designed to evaluate the efficacy and tolerability of escitalopram in the treatment of major depressive disorder.

Method: Outpatients with an ongoing DSM-IV major depressive episode (N=491) were randomly assigned to placebo, escitalopram, 10 mg/day, escitalopram, 20 mg/day, or citalopram, 40 mg/day, and entered an 8-week double-blind treatment period following a 1-week single-blind placebo lead-in. Clinical response was evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), the 24-item Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions (CGI) scales, the Hamilton Rating Scale for Anxiety (HAM-A), and patient-rated quality-of-life scales.

Results: Escitalopram, at both doses, produced significant improvement at study endpoint relative to placebo on all measures of depression; significant separation of escitalopram from placebo was observed within 1 week of double-blind treatment. Citalopram treatment also significantly improved depressive symptomatology compared with placebo; however, escitalopram, 10 mg/day, was at least as effective as citalopram, 40 mg/day, at endpoint. Anxiety symptoms and quality of life were also significantly improved by escitalopram compared with placebo. The incidence of discontinuations due to adverse events for the escitalopram 10 mg/day group was not different from the placebo group (4.2% vs. 2.5%; p=.50), and not different for the escitalopram 20 mg/day group and the citalopram 40 mg/day group (10.4% vs. 8.8%; p=.83).

Conclusion: Escitalopram, a single isomer SSRI, is well-tolerated and has demonstrated antidepressant efficacy at a dose of 10 mg/day.