Background: Traditional randomized withdrawal studies have assessed the efficacy of antidepressants for reducing relapse and recurrence of major depressive episodes (MDEs) but have not compared dose reduction, increase, or maintenance within the same study.
Methods: Here we present the development, implementation, and preliminary data from the open-label period of an ongoing phase 4, non-traditional, randomized withdrawal study. Designed to evaluate the efficacy of vortioxetine across its approved dose range for relapse prevention, the study enrolled adult patients with recurrent major depressive disorder (MDD), Montgomery-Åsberg Depression Rating Scale (MADRS) ≥ 26, and history of ≥2 MDEs. After a 16-week, open-label, fixed-dose (vortioxetine 10 mg once daily) period, patients meeting response criteria (≥50% reduction in MADRS total score, Weeks 8-16) and remission criteria (MADRS total score ≤12, Weeks 14 and 16) were randomized to vortioxetine 5, 10, or 20 mg, or placebo in a 32-week double-blind treatment period.
Results: Of 1106 patients enrolled, 510 completed the open-label period (mean age: 45.7 years; mean MADRS = 5.0; predominantly female, white, and never smokers) and were eligible for randomization in the ongoing double-blind period.
Limitations: Study is ongoing; only data from the open-label period are available for evaluation.
Conclusions: Preliminary analysis suggests that patient baseline characteristics were not a factor in response to and stabilization with vortioxetine during the open-label period. The lack of flexibility in dosing, however, may have reduced the number of patients qualifying for randomization. This study design may provide useful information for optimizing the long-term efficacy and tolerability of vortioxetine treatment for MDD.
Keywords: Antidepressant; Major depressive disorder; Major depressive episode; Randomized withdrawal; Relapse prevention; Vortioxetine.
Copyright © 2020. Published by Elsevier B.V.