Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response.

This study aimed to evaluate if efficacy and tolerability of switching to vortioxetine is independent of previous SSRI or SNRI treatment in patients who had been inadequately treated for their current major depressive episode. Patients from a double-blind, 12-week comparator study were randomized (1:1) to vortioxetine (10-20 mg/day) or agomelatine (25-50 mg/day). The pre-defined primary efficacy endpoint was change from baseline to week 8 in MADRS total score analyzed by MMRM. An ANCOVA-LOCF was conducted as a sensitivity analysis. These analyses were repeated in subgroups according to previous antidepressant treatment. In the overall population, vortioxetine (n = 252) was significantly superior to agomelatine (n = 241) by -2.2 MADRS points (p < 0.01) at week 8. ∼77% (n = 189/vortioxetine, n = 188/agomelatine) were previously treated with an SSRI (citalopram, escitalopram, paroxetine, sertraline) and ∼23% (n = 62/vortioxetine, n = 52/agomelatine) with an SNRI (duloxetine, venlafaxine). Baseline characteristics were similar in all subgroups. Treatment differences (MMRM) in MADRS total score were -2.6 and -2.3 (n = 164/vortioxetine, n = 150/agomelatine) (p < 0.01) for patients switching from an SSRI and -1.8 and -1.5 (n = 56/vortioxetine, n = 40/agomelatine) (p > 0.05) from an SNRI at weeks 8 and 12, respectively; non-significant improvements were seen for each of the 6 previous antidepressants. Improvements in HAM-A, CGI-I, and EQ-5D scales were significant for the SSRI subgroup and non-significant for the SNRI subgroup. Withdrawal and adverse event rates were similar, regardless of previous SSRI or SNRI treatment. These subgroup analyses showed statistical superiority of vortioxetine to agomelatine in inadequate responders to SSRIs and statistically non-significant improvements in the smaller SNRI subgroup, while being equally well tolerated. TRIAL REGISTRATION: This study has the ClinicalTrials.gov identifier NCT01488071.