Comparison of vortioxetine versus venlafaxine XR in adults in Asia with major depressive disorder: a randomized, double-blind study

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- Asberg 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.