A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder

Abstract

In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. Study limitations are discussed, including patient characteristics, MDD severity, drug dosing, and aspects of trial design. Both doses of vortioxetine were well tolerated. This trial has been registered at clinicaltrials.gov #NCT00672620.

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder

“…In the current analysis, functional remission (SDS total score ≤6) at week 6/8 was 25.5%, 30.4%, 30.9%, and 31.2% for vortioxetine 5, 10, 15, and 20 mg, respectively. Symptomatic remission rates (MADRS total score ≤10) at these doses in the individual studies ranged from 28.8% to 36.0% for vortioxetine 5 mg, 21.4%–36.0% for vortioxetine 10 mg, 23.9%–34.9% for vortioxetine 15 mg, and 29.3%–38.4% for vortioxetine 20 mg, respectively (Baldwin et al., 2012; Boulenger et al., 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Jain et al., 2013; Mahableshwarkar, Jacobsen, Chen, et al., 2015; Mahableshwarkar, Jacobsen, Serenko, et al., 2015; Mahableshwarkar et al., 2013). …”

“…Additionally, vortioxetine 10 mg daily demonstrated clinically significant benefits on all aspects of functioning (SDS single‐item scores) in the total population as well as on overall functioning (SDS total score) in patients with severe MDD and/or significant functional impairment or high anxiety symptoms at baseline. These findings are consistent with the results of the individual studies, where vortioxetine administration was associated with improvements in patient functioning as well as in depressive symptoms (Baldwin et al., 2012; Boulenger et al., 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Jain et al., 2013; Mahableshwarkar, Jacobsen, Chen, et al., 2015; Mahableshwarkar, Jacobsen, Serenko, et al., 2015; Mahableshwarkar et al., 2013; Takeda, 2013). …”

“…Thus, data from nine short‐term (6/8 weeks) multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group, fixed‐dose clinical studies of vortioxetine conducted in adults (aged 18–75 years) with MDD were analyzed. The details of the study design and the results of the nine included trials have been previously published (Baldwin et al., 2012; Boulenger et al., 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Jain et al., 2013; Mahableshwarkar, Jacobsen, Chen, et al., 2015; Mahableshwarkar, Jacobsen, Serenko, et al., 2015; Mahableshwarkar et al., 2013; Takeda, 2013). Table 1 provides a summary of treatment dosages, number of participants in each dosage arm, treatment duration, and key inclusion criteria for each of the trials included in this meta‐analysis.…”

“…All patients enrolled in these studies met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR; American Psychiatric Association (APA), 2000) criteria for a major depressive episode lasting ≥3 months and were ≥18 years old. Additionally, patients were required to have Montgomery‐Åsberg Depression Rating Scale (MADRS; Montgomery & Asberg, 1979) scores ≥22 (NCT00672620, Mahableshwarkar et al., 2013), ≥30 (NCT00672958, Jain et al., 2013) or ≥26 (all other trials; Baldwin et al., 2012; Boulenger et al., 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Mahableshwarkar, Jacobsen, Chen, et al., 2015; Mahableshwarkar, Jacobsen, Serenko, et al., 2015; Takeda, 2013; Table 1). …”

“…The efficacy and safety of vortioxetine in patients with MDD has been demonstrated in a series of short‐ and long‐term studies (Alvarez et al., 2012; Boulenger, Loft, & Olsen, 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Katona, Hansen, & Olsen, 2012; Mahableshwarkar, Jacobsen, Chen, et al., 2015; McIntyre, Lophaven, & Olsen, 2014; Montgomery, Nielsen, et al., 2014). The effects of vortioxetine on general functioning were assessed (with the SDS) as secondary measures in a subset of short‐term clinical trials (Baldwin, Loft, & Dragheim, 2012; Boulenger et al., 2014; Henigsberg et al., 2012; Jacobsen et al., 2015; Jain et al., 2013; Mahableshwarkar, Jacobsen, & Chen, 2013; Mahableshwarkar, Jacobsen, Chen, et al., 2015; Mahableshwarkar, Jacobsen, Serenko, et al., 2015; Takeda, 2013). The purpose of this post hoc meta‐analysis was to analyze the SDS results from these studies to determine the effect of vortioxetine on overall patient functioning as well as the proportion of patients who achieved functional remission versus placebo.…”