Intravenous vortioxetine to accelerate onset of effect in major depressive disorder: a 7-day randomized, double-blind, placebo-controlled exploratory study

Elmars Rancans, Janos Zambori, Mads Dalsgaard, Corine Baayen, Johan Areberg, Anders Ettrup, Ioana Florea, Elmars Rancans, Janos Zambori, Mads Dalsgaard, Corine Baayen, Johan Areberg, Anders Ettrup, Ioana Florea

Abstract

This 7-day randomized, double-blind, placebo-controlled fixed-dose study (NCT03766867) explored the potential for accelerating the onset of antidepressant efficacy of single-dose intravenous (IV) vortioxetine at oral vortioxetine treatment initiation. Patients (ages 18-65 years) hospitalized per standard-of-care with major depressive disorder, who were currently treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor for a major depressive episode [Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 30], received one dose of single-blind IV placebo (1-day placebo lead-in period) before being randomly switched to either single-dose IV vortioxetine 25 mg plus daily oral vortioxetine 10 mg (n = 39), or IV placebo plus daily oral placebo (n = 41). In the placebo lead-in period, patients improved slightly by 0.6 MADRS-6 point; however, at day 1 after randomization, both treatment groups had improved by approximately 3 MADRS-6 points (mean difference = -0.8; P = 0.263), the study thus not meeting its primary endpoint. Similar results were seen for other outcomes except a numerically larger improvement in anxiety symptoms with vortioxetine vs placebo. Pharmacokinetic data confirmed that IV vortioxetine facilitated reaching steady-state plasma concentration within 24 h. IV plus oral vortioxetine was well tolerated, with low levels of nausea as the most common adverse event.

Conflict of interest statement

E.R. has received research grants from Gedeon Richter and Lundbeck, and speaker honoraria from and is a member of advisory panels for Abbvie, Gedeon Richter, Grindex, Janssen Cilag, Lundbeck, Servier, and Zentiva. J.Z., M.D., C.B., J.A., A.E., and I.F. are employees of H. Lundbeck A/S.

Figures

Fig. 1
Fig. 1
Patient disposition.
Fig. 2
Fig. 2
MADRS-6 subscale score (a) and MADRS total score (b) across study period (FAS, MMRM). Treatment differences are based on the least squares mean; error bars represent standard errors. FAS, full-analysis set; MADRS, Montgomery–Åsberg Depression Scale; MMRM, mixed model for repeated measurements.

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Source: PubMed

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