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.