OBJECTIVE: This randomised, double-blind, 12-week study compared efficacy and 
tolerability of flexible-dose treatment with vortioxetine(10-20 mg/day) versus 
agomelatine (25-50 mg/day) in major depressive disorder patients with inadequate 
response to selective serotonin reuptake inhibitor 
(SSRI)/serotonin-noradrenaline reuptake inhibitor (SNRI) monotherapy.
METHODS: Patients were switched directly from SSRI/SNRI to vortioxetine or 
agomelatine. Primary endpoint was change from baseline to week 8 in the 
Montgomery-Åsberg Depression Rating Scale (MADRS) total score analysed by mixed 
model for repeated measurements, using a noninferiority test followed by a 
superiority test. Secondary endpoints included response and remission rates, 
anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, 
overall functioning (Sheehan Disability Scale), health-related quality of 
life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and 
family functioning (Depression and Family Functioning Scale).
RESULTS: Primary endpoint noninferiority was established and vortioxetine (n = 
252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01). 
Vortioxetine was also significantly superior in response and remission rates at 
weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global 
Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 
onwards; work limitation questionnaire at week 8 and Depression and Family 
Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse 
events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were 
nausea, headache, dizziness and somnolence.
CONCLUSIONS: Vortioxetine was noninferior and significantly superior to 
agomelatine in major depressive disorder patients with previous inadequate 
response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and 
well tolerated.