A randomised, double‐blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine

Abstract

ObjectiveThis randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine (10–20 mg/day) versus agomelatine (25–50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin–noradrenaline reuptake inhibitor (SNRI) monotherapy.MethodsPatients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms (Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life (EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).ResultsPrimary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p < 0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence.ConclusionsVortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated.

A Comparative Study of Efficacy and Safety of Agomelatine and Escitalopram in Major Depressive Disorder

“…Hence, the present study confirms the good tolerability of agomelatine. This is in line with other studies on agomelatine [21,[23][24][25].…”

“…Remission is uncommon in short-term studies, because it often occurs beyond the study period [21]. Adverse effects were considered responsible for poor patient compliance to antidepressant treatment [22].…”

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

“…The SDS is a validated measure of functional impairment that has demonstrated sensitivity to impairment and the effects of treatment across a wide range of disorders, including MDD (Sheehan & Sheehan, 2008). The SDS has been used to assess functional improvement in association with improvements in depressive symptoms for duloxetine (Mancini et al., 2012; Oakes et al., 2012; Sheehan et al., 2011; Wise et al., 2008), desvenlafaxine (Dunlop et al., 2011; Guico‐Pabia et al., 2012; Soares et al., 2009), paroxetine (Wise et al., 2008), bupropion (Hewett et al., 2010; Soczynska et al., 2014), escitalopram (Romera et al., 2012; Soczynska et al., 2014), venlafaxine (Fann et al., 2015; Hewett et al., 2010), levomilnacipran (Asnis et al., 2013; Sambunaris, Bose, et al., 2014), and agomelatine (Montgomery, Nielsen, et al., 2014; Zajecka et al., 2010) with results that have been variable with respect to clinical significance; however, many of these antidepressants showed significant differences versus placebo in the change from baseline versus placebo in the SDS total score when patients were stratified by baseline depressive symptom severity. A recent pooled analysis showed that treatment with duloxetine ( n  = 1,029) and SSRIs ( n  = 835) resulted in significantly greater improvements in the SDS total score (∆ −1.9, p  <   .001; ∆ −1.7, p  <   .01, respectively) compared to placebo ( n  = 329).…”

“…In general, treatment with vortioxetine has demonstrated a similar quantitative effect in patients with MDD. In a direct comparison to agomelatine (25–50 mg) in patients with an inadequate response to SSRI/SNRI monotherapy, vortioxetine (10–20 mg) had significantly greater reductions on the SDS total and item scores after 8 and 12 weeks of treatment (Montgomery, Nielsen, et al., 2014). Vortioxetine 10 mg has also demonstrated numerically larger changes from baseline on the SDS total and item scores than venlafaxine XR 150 mg/day after 8 weeks of treatment in adult patients with MDD in Asia (Wang, Gislum, Filippov, & Montgomery, 2015).…”

“…In preclinical studies, vortioxetine has demonstrated effects on serotonergic, noradrenergic, dopaminergic, cholinergic, norepinephrinergic, acetylcholinergic, histaminergic, gabanergic, and glutamatergic neurotransmission (Bang‐Andersen et al., 2011; Mork et al., 2012; Sanchez, Asin, & Artigas, 2015). 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).…”