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

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

2014 Curr Med Res Opin

Llorca, P. M. | Lancon, C. | Brignone, M. | Rive, B. | Salah, S. | Ereshefsky, L. | Francois, C. | Volume: 30, Issue: 12, Pages: 2589-606, Acetamides/therapeutic use, Adult, Aged, Antidepressive Agents/*therapeutic use, Benzofurans/therapeutic use, Citalopram/therapeutic use, Cyclohexanols/therapeutic use, Depressive Disorder, Major/*drug therapy, Desvenlafaxine Succinate, Duloxetine Hydrochloride, Female, Humans, Hypnotics and Sedatives/therapeutic use, Indoles/therapeutic use, Male, Middle Aged, Piperazines/*therapeutic use, Serotonin Uptake Inhibitors/*therapeutic use, Sertraline/therapeutic use, Sulfides/*therapeutic use, Thiophenes/therapeutic use, Venlafaxine Hydrochloride, Vilazodone Hydrochloride, Antidepressants, Comparative evidence, Major depressive disorder, Vortioxetine,

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.

https://www.doi.org/10.1185/03007995.2014.969566