Intravenous vortioxetine to accelerate onset of effect in major depressive disorder: a 2-week, randomized, double-blind, placebo-controlled study

Eduard Vieta, Ioana Florea, Simon Nitschky Schmidt, Johan Areberg, Anders Ettrup, Eduard Vieta, Ioana Florea, Simon Nitschky Schmidt, Johan Areberg, Anders Ettrup

Abstract

This 2-week randomized, double-blind, placebo-controlled fixed-dose study (NCT02919501) explored the potential of accelerating onset of antidepressant efficacy and plasma exposure with single-dose intravenous vortioxetine at oral vortioxetine treatment initiation. Outpatients (ages 18-65 years) with major depressive disorder and a current depressive episode (Montgomery Åsberg Depression Rating Scale total score ≥30) were randomized to an initial single dose of either intravenous vortioxetine 17 mg (n = 27) or intravenous placebo (n = 28), both treatments followed by 2 weeks of oral vortioxetine (10 mg/day). From baseline to day 7, both groups exhibited fast and substantial improvements by approximately 14 Montgomery Åsberg Depression Rating Scale points, with no statistically significant treatment difference for this primary endpoint. Improvements were substantial already within 24 hours, with numerical treatment differences of 1.3 and 1.6 points at days 1 and 3, respectively, in favour of intravenous vortioxetine + oral vortioxetine. Pharmacokinetic data confirmed that intravenous vortioxetine facilitated reaching steady-state plasma concentration within 24 hours. Intravenous vortioxetine + oral vortioxetine was safe and well-tolerated, with nausea as the most common adverse event. This study supported intravenous vortioxetine as a means of rapidly reaching therapeutic vortioxetine blood levels.

Figures

Fig. 1
Fig. 1
Patient disposition. *Lost to follow-up.
Fig. 2
Fig. 2
Efficacy assessments across study period (FAS, MMRM). IV vortioxetine + oral vortioxetine, n = 27; IV placebo + oral vortioxetine, n = 28. Treatment differences are based on the least squares means; error bars represent standard errors. CGI-I, Clinical Global Impressions-Improvement; CGI-S, Clinical Global Impressions-Severity of Illness; FAS, full-analysis set; HADS-A, Hospital Anxiety and Depression Scale-Anxiety; HADS-D, Hospital Anxiety and Depression Scale-Depression; IV, intravenous; MADRS, Montgomery Åsberg Depression Scale; MMRM, mixed model for repeated measurements.
Fig. 3
Fig. 3
Simulated and estimated plasma concentration. IV vortioxetine + oral vortioxetine, n = 27; IV placebo + oral vortioxetine, n = 28. Cmax, maximum concentrations; IV, intravenous; PopPK, population pharmacokinetics.

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