Early Non-Response in Patients with Severe Depression: Escitalopram Up-Titration versus Switch to Duloxetine
Clinical Drug Investigation, 05/21/2012
Bose A et al. – In initial non–responders to escitalopram 10 mg/day, dose escalation to 20 mg/day provided better efficacy than switching to duloxetine 60 mg/day, while discontinuations for any reasons and adverse events were similar.Methods
- This was an active–controlled, parallel–group, double–blind, randomized study in a general community comparing escitalopram and duloxetine in patients with severe depression; patients who did not respond (<50% Montgomery–Åsberg Depression Rating Scale [MADRS] improvement) to 2 weeks of single–blind escitalopram 10 mg/day during the lead–in period were randomized to 8 weeks of double–blind treatment.
- 571 male and female outpatients aged 18–65 years with severe depression (MADRS total score ≥30) participated in the study and received at least one dose of escitalopram 10 mg/day in the single–blind lead–in phase.
- During the double–blind randomized phase, 474 patients who did not respond to lead–in escitalopram were randomized and received treatment with escitalopram 20 mg (n = 229) or duloxetine 60 mg (n = 245).
- Treatment was single–blind escitalopram 10 mg/day during a 2–week lead–in followed by 8–week double–blind escitalopram 20 mg/day or duloxetine 60 mg/day.
- The main outcome measure was time to all–cause premature study discontinuation.
- There was no difference in time to all–cause discontinuation between groups (hazard ratio escitalopram/duloxetine = 0.95 [95% CI 0.64, 1.41]; p = 0.727).
- Treatment with escitalopram compared with duloxetine resulted in significant improvement in MADRS total score at the end of week 8 (least squares mean difference [LSMD] =–1.87 [95% CI –3.60, –0.14]; p = 0.034) using last observation carried forward (LOCF) analysis.
- Significantly more escitalopram (54%) than duloxetine (42%) patients achieved remission (MADRS ≤10) by week 8 (p = 0.013).
- Adverse events were similar between the two treatment groups.