A randomized, double-blind, 6-week prospective pilot study on the efficacy and safety of dose escalation in non-remitters in comparison to those of the standard dose of escitalopram for major depressive disorder

Abstract

Background: Escalating doses of selective serotonin reuptake inhibitors are often used to treat patients with a suboptimal response to the standard dose. This study assessed the efficacy and safety of dose escalation of escitalopram, up to 30 mg, in non-remitters with major depressive disorder (MDD) after treatment with the standard dose.

Method: We recruited 98 patients with MDD (aged 18-65 years). After 4 weeks of open-label treatment with 10-20 mg of escitalopram per day, non-remitters [Montgomery-Åsberg Depression Rating Scale (MADRS) score > 10] were randomized 1:1 for double-blind treatment with either escitalopram (30 mg per day) or escitalopram (20 mg per day) plus placebo for 6 weeks. The primary efficacy outcome was a change in the total MADRS score.

Results: After 4 weeks of open-label treatment, 12 patients achieved remission, and 36 dropped out, leaving 50 non-remitters, of whom 44 (88%) completed the double-blind study. The primary outcome measure, the least-squares mean (standard error) change in the total MADRS score at week 6 was significantly different (p = 0.046) between the groups [-8.0 (1.2) in the placebo dose-escalation and -11.8 (1.2) in the escitalopram dose-escalation]. The dose escalation of escitalopram was well tolerated. However, the response and remission rates and quality of life showed no significant differences.

Limitations: Small sample size and short follow-up period CONCLUSION: This study suggests that dose escalation of escitalopram up to 30 mg per day may be beneficial for the treatment of depressive symptoms in non-remitters after standard (10-20 mg/day) treatment.

Keywords: Dose escalation; Escitalopram; Major depressive disorder; Non-remitter; Randomized controlled trial.