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

Abstract

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.

Keywords::

• Comparator study
• Major depressive disorder
• Venlafaxine XR
• Vortioxetine

Transparency

Declaration of funding

H. Lundbeck A/S sponsored the study as part of a joint clinical development program with the Takeda Pharmaceutical Company, Ltd. Lundbeck was involved in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.

Declaration of financial/other relationships

G.W. has disclosed that he has received grant funding as well as honoraria and consultancy fees from Lundbeck, Pfizer, MSD, Janssen, Eli Lilly and AstraZeneca. M.G. and G.F. have disclosed that they are employees of Lundbeck. S.M. has disclosed that he has received honoraria and/or has participated in advisory boards on behalf of: Alkermes, AstraZeneca, Grunenthal, Johnson & Johnson, Lundbeck, Merck, Merz, M’s Science Corporation, Otsuka Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, PharmaNeuroBoost, Richter, Roche, Servier, Synosis, Takeda, Theracos, Targacept, Transcept and Xytis.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank D.J. Simpson (H. Lundbeck A/S) for providing support in the preparation, revision, and editing of the manuscript. The authors are entirely responsible for the scientific content of this paper.

The authors gratefully acknowledge the participation of the following investigators in the psychiatric sites in this study. China: Gang Wang, Xiufeng Xu, Lehua Li, Fude Yang, Keqing Li, Hongyan Zhang, Lina Wang, Jianguo Shi, Chengge Gao, Shiping Xie, Zhenhuan Zhao, Huafang Li, Tao Li, Kerang Zhang, Qingrong Tan; South Korea: Se Joo Kim, Yong Min Ahn, Won-Myong Bahk, Sang-Hyuk Lee, Tae-Kyou Choi, Han-Yong Jung, Jin Pyo Hong, Jee Hyun Ha; Taiwan: Ching-Yen Chen, Yuan-Hwa Chou, Li-Ren Chang, Tzu-Ting Chen, Ching-Hua Lin, Lih-Chih Jou, Hsin-Chien Lee, Yen-Kuan Yang; Thailand: Manit Srisurapanont, Vasu Chantarasak.