Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies

Abstract

Introduction:

Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).

Methods:

We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events).

Results:

For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, −0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, −0.05 (p = 0.70); sertraline, −0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, −0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking.

Conclusion:

These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity).

Key messages:

Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.

Keywords::

• Antidepressants
• Comparative evidence
• Major depressive disorder
• Vortioxetine

Transparency

Declaration of funding

This work was funded by H. Lundbeck A/S, the manufacturer of vortioxetine.

Declaration of financial/other relationships

P.-M.L. has disclosed that he has received grants from Lundbeck, Sevier and Lilly, and he is on the board of Sevier and Lundbeck. C.L. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article. M.B., B.R. and C.F. have disclosed they are employees of Lundbeck. S.S. has disclosed that he was an employee of Keyrus Biopharm during the time of the study, and provided statistical consultation to Lundbeck. L.E. has disclosed that he is an employee of PAREXEL International, a company that received funding from Lundbeck to conduct this study.

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.