San Francisco—After 8 weeks of treatment, patients with major depressive disorder (MDD) who received 20 mg of vortioxetine had a significant reduction in Montgomery-Asberg Depression Rating Scale (MADRS) total score compared with patients who received a placebo, according to a phase 3, multicenter, randomized, double-blind study.
At weeks 4 and 6, patients who received 20 mg of vortioxetine had a significant MADRS total score reduction compared with the placebo group, but the difference was not significant at week 8.
Results were presented during a poster session at the APA meeting. The posted was titled A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Vortioxetine 10 mg and 20 mg in Adults with Major Depressive Disorder.
In December 2012, Takeda Pharmaceutical Company Limited and H. Lundbeck A/S announced they had submitted a new drug application to the FDA for the approval of vortioxetine. The drug is a combination of direct modulation of receptor activity and inhibition of the serotonin transporter.
In this study, the authors randomized 462 patients with MDD in a 1:1:1 ratio to receive 10 mg of vortioxetine, 20 mg of vortioxetine, or placebo for 8 weeks. Patients in the 20-mg vortioxetine group received 10 mg of the drug for the first week before switching to 20 mg for the remainder of the trial. After 8 weeks, patients enrolled for 2 weeks in a single-blind study to assess potential discontinuation symptoms.
The 3 groups were well balanced. Mean age was 43 years, 27% of patients were male, and 70% were white.
At week 8, the MADRS total score was reduced by 10.8 points in the placebo group compared with a reduction of 13.0 points in the 10-mg vortioxetine group (P=.058) and 14.4 points in the 20-mg vortioxetine group (P=.002). The significant difference between the 20-mg vortioxetine group and the placebo group began at week 4 and lasted through week 8.
In addition, 28.4% of patients in the placebo group had at least a 50% decrease in total MADRS score at week 8 compared with 33.8% of patients in the 10-mg vortioxetine group (P=.301) and 39.2% of patients in the 20-mg vortioxetine group (P=.044). Further, 14.2% of patients in the placebo group had a MADRS total score of ≤10 at week 8 compared with 21.4% of patients in the 10-mg vortioxetine group (P=.093) and 22.3% of patients in the 20-mg vortioxetine group (P=.059).
Compared with the placebo group, there was a 0.2 point reduction in Clinical Global Impressions-Improvement score for patients in the 10-mg vortioxetine group (P=.119) and a 0.3 point reduction in the 20-mg vortioxetine group (P=.024). Also, compared with the placebo group, there was a 1.39 point reduction in Sheehan Disability Scale total score at 8 weeks for patients in the 10-mg vortioxetine group (P=.183) and a 2.4 point reduction in the 20-mg vortioxetine group (P=.025).
The incidence of treatment-emergent adverse events was 62.4% in the placebo group, 73.5% in the 10-mg vortioxetine group, and 68.7% in the 20-mg vortioxetine group. The authors noted that most of the adverse events were mild or moderate, although 17 patients discontinued the study because of an adverse event, including 2 in the placebo group, 8 in the 10-mg vortioxetine group, and 7 in the 20-mg vortioxetine group.
This study was supported by Takeda Pharmaceutical Company Limited.