Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension

Abstract

Objective. This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features).Method. Patients with MDD plus two or three manic symptoms (defined as per the DSM-5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20-60 mg/day (n = 109) or placebo (n = 100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n = 48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery-Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤ 3) at week 6, and at both months 1 and 3 of the extension study ("sustained recovery").Results. A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed crosssectionally) compared to placebo (12.2%, p = 0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p = 0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%).Conclusions. In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.

Oral and long‐acting antipsychotics for relapse prevention in schizophrenia‐spectrum disorders: a network meta‐analysis of 92 randomized trials including 22,645 participants

“…After removing duplicates and examining titles and abstracts, we selected 514 records for full‐text assessment. Of these, 100 primary studies were eligible for inclusion (corresponding to 99 full‐text articles 57‐155 , as one paper reported on two trials). Of these, 92 studies, including 22,645 participants, provided data for ≥1 outcome of interest (see Figure 1).…”

Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines

“…Another further major flaw of the literature is that mixed depressive patients are not usually reported in depression RCT (24). Furthermore, the evidence about the treatment of MDD with MFS is still scant and limited to lurasidone (134)(135)(136)(137)173). Accordingly, the guidelines included in this systematic review did not differentiate the treatment for MDE with MFS in the context of BD or MDD (43).…”

“…As for lurasidone, it was not possible to rate the evidence for the long-term treatment because in the three studies aimed at investigating the efficacy of lurasidone vs. placebo including mixed patients (170)(171)(172), no separate outcome has been reported for this group. A recent post hoc analysis evaluating remission and recovery associated with lurasidone in the treatment of MDD with mixed features (173) reported patients treated with lurasidone significantly achieved recovery compared to placebo after 6 weeks of treatment, but this study was not included in the considered guidelines.…”

Modulation of anterior cingulate cortex reward and penalty signalling in medication-naive young-adult subjects with depressive symptoms following acute dose lurasidone

“…In this paper, we test whether an acute dose of 20 mg lurasidone, a D 2 receptor antagonist (Loebel and Citrome, 2015) with demonstrated antidepressant properties in monotherapy and in combination treatment (Loebel et al ., 2014 a , 2014 b ; Suppes et al ., 2016 a ; Goldberg et al ., 2017), influences reward and penalty signal in depression. Lurasidone was selected because it is the most recently licensed dopamine antagonist with antidepressant properties and there is no information with regards to its effects on brain reward and penalty signalling (Loebel et al ., 2014 a , 2014 b ; Nelson et al ., 2015; Nierenberg et al ., 2015; Suppes et al ., 2016 a , 2016 b ; Goldberg et al ., 2017). We employ a randomised, placebo-controlled cross-over design with functional magnetic resonance imaging (fMRI) and arterial spin labelling (ASL) imaging acquired on two separate occasions per individual.…”