OBJECTIVE: This randomized, double-blind 8 week study compared the efficacy and tolerability of fixed-dose treatment with vortioxetine (10 mg/day) and venlafaxine extended release (XR) (150 mg/day) in major depressive disorder (MDD) patients.
RESEARCH DESIGN AND METHODS: Patients aged 18-65 years with a primary diagnosis of recurrent MDD, a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 and a Clinical Global Impression-Severity (CGI-S) score ≥4 were randomized (1:1) to treatment with either vortioxetine or venlafaxine XR. The primary endpoint was change from baseline to Week 8 in MADRS total score (analysis of covariance [ANCOVA], full-analysis set [FAS], last observation carried forward [LOCF]), using a non-inferiority margin of +2.5 points. Pre-specified secondary endpoints included MADRS response and remission rates, anxiety symptoms (HAM-A), CGI, overall functioning (SDS), and health-related quality of life (Q-LES-Q).
CLINICAL TRIAL REGISTRATION: This study (SOLUTION) has the www.ClinicalTrials.gov identifier: NCT01571453.
RESULTS: On the primary efficacy endpoint at Week 8, non-inferiority was established with a difference of -1.2 MADRS points in favor of vortioxetine (95% CI: -3.0 to 0.6). The MADRS total score decreased (improved) from 32.3 ± 4.6 at baseline to 13.6 ± 9.6 (vortioxetine: n = 209) and from 32.3 ± 4.5 to 14.8 ± 10.4 (venlafaxine XR: n = 215) (FAS, LOCF). At Week 8, the HAM-A and SDS total scores, CGI and Q-LES-Q scores, and response and remission rates demonstrated similar improvement for vortioxetine and venlafaxine XR, with remission rates (MADRS ≤10) of 43.1% (vortioxetine) versus 41.4% (venlafaxine XR) (LOCF). Fewer vortioxetine than venlafaxine XR patients withdrew for any reason (18.0% versus 27.4%) or for adverse events (6.6% versus 13.7%). The most frequent adverse events (≥5%) for both treatments were nausea, dizziness, headache, and dry mouth. In addition, accidental overdose, decreased appetite, constipation and insomnia were reported by (≥5%) of patients treated with venlafaxine XR.
LIMITATIONS: The inclusion and exclusion criteria may limit the generalizability of the study. Since patients with a history of lack of response to venlafaxine XR were excluded from this study, there is a selection bias in favor of venlafaxine XR.
CONCLUSION: Vortioxetine was at least as efficacious as venlafaxine XR and was safe and better tolerated than venlafaxine XR.
