Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies. (December 2014)

• Record Type: Journal Article
• Authors: Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Rive, Benoît; Salah, Samir; Ereshefsky, Larry; Francois, Clément
• Is Part Of: Current medical research and opinion. Volume 30:Number 12(2014:Dec.)
• Page Start: 2589
• Page End: 2606
• Publication Date: 2014-12
• Subjects: Clinical medicine -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1185/03007995.2014.969566
• Languages: English
• ISSNs: 0300-7995

Abstract

<abstract> <title>Abstract</title> <sec id="ss1"> <title>Introduction:</title> <p>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).</p> </sec> <sec id="ss2"> <title>Methods:</title> <p>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).</p> </sec> <sec id="ss3"> <title>Results:</title> <p>For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, −0.16 (<italic>p</italic> = 0.11); desvenlafaxine, 0.03 (<italic>p</italic> = 0.80); duloxetine, 0.09 (<italic>p</italic> = 0.42); escitalopram, −0.05 (<italic>p</italic> = 0.70); sertraline, −0.04 (<italic>p</italic> = 0.83); venlafaxine IR/XR, 0.12 (<italic>p</italic> = 0.33); and vilazodone, −0.25 (<italic>p</italic> = 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 (<italic>p</italic> = 0.03); desvenlafaxine, 0.58 (<italic>p</italic> = 0.04); duloxetine, 0.75 (<italic>p</italic> = 0.26); escitalopram, 0.67 (<italic>p</italic> = 0.28); sertraline, 0.30 (<italic>p</italic> = 0.01); venlafaxine, 0.47 (<italic>p</italic> = 0.01); and vilazodone, 0.64 (<italic>p</italic> = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking.</p> </sec> <sec id="ss4"> <title>Conclusion:</title> <p>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).</p> </sec> <sec id="ss5"> <title>Key messages:</title> <p>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.</p> </sec> </abstract>