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.

Joseph F Goldberg,Daisy Ng-Mak,Cynthia Siu,Chien-Chia Chuang,Antony Loebel,Krithika Rajagopalan

doi:10.1017/s1092852917000025

Abstract

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). 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"). A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed cross-sectionally) 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%). 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.

Highlights

Manic symptoms below the threshold for hypomania are prevalent in people with major depressive disorder (MDD).[1,2,3,4,5,6,7] In the National Comorbidity Survey Replication (NCS–R) study, a nationally representative, face-to-face, household survey of the U.S population conducted between February of 2001 and Downloaded from https://www.cambridge.org/core
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 that was sustained at month 3 of the extension study
A post-hoc analysis was conducted using data from a previously reported double-blind, placebo-controlled, 6-week trial in patients with major depressive disorder associated with subthreshold hypomanic symptoms

Summary

Introduction

Manic symptoms below the threshold for hypomania (mixed features) are prevalent in people with major depressive disorder (MDD).[1,2,3,4,5,6,7] In the National Comorbidity Survey Replication (NCS–R) study, a nationally representative, face-to-face, household survey of the U.S population conducted between February of 2001 and Downloaded from https://www.cambridge.org/core. Lurasidone is an atypical antipsychotic agent with high affinity for D2, 5-HT2A, and 5-HT7 receptors (Ki = 1, 0.5, and 0.495 nM, respectively).[15] In animal models, the antidepressant effect of lurasidone has been shown to be mediated in part by antagonist activity at the 5-HT7 receptor.[16,17] Lurasidone has demonstrated efficacy in the treatment of major depressive episodes associated with bipolar I disorder (bipolar depression), both as a monotherapy and as an adjunctive therapy with lithium or valproate.[18,19] A recent placebo-controlled trial demonstrated the efficacy and safety of lurasidone for MDD with subthreshold hypomanic symptoms.[20]

Methods

Results

Discussion

Conclusion