EPA-0425 – Effect of Lurasidone on Depressive Symptoms in Patients with Schizophrenia

Abstract

Introduction:

Clinically significant depressive symptoms are common in schizophrenia, and are associated with greater functional impairment and worse outcomes.

Objectives:

To evaluate the effect of lurasidone in patients with a DSM-IV-TR diagnosis of schizophrenia who presented with significant depressive symptoms.

Methods:

Pooled data were analyzed from 4, six-week, double-blind, placebo-controlled schizophrenia trials, with available MADRS data. Patients with an acute exacerbation of schizophrenia were randomized to fixed, 40–160 mg (n=902) once-daily doses of lurasidone, or placebo (n=439). LOCF-endpoint data were analyzed using ANCOVA. MADRS remission was defined as an endpoint score <10.

Results:

At baseline, 45.0% and 24.5% of subjects had a MADRS score of ≥12, and ≥16 respectively. Treatment with lurasidone was associated with significantly greater improvement in the MADRS at LOCF-endpoint compared with placebo in the total sample (-2.8 vs. -1.4; p<0.001), and in each baseline depression severity subgroup: MADRS ≥12 (-6.7 vs. -4.8; p<0.005), and MADRS ≥16 (-9.3 vs. -6.3; p<0.005). Overall, the largest effect size was observed for the 160 mg dose of lurasidone (0.43). For the subgroup with MADRS≥16 at baseline, higher depression remission rates were observed for lurasidone 160 mg (47.8%) compared with lurasidone 80 mg (38.6%) and lurasidone 40 mg (28.6%).

Conclusions:

In this pooled, post-hoc analysis, 40-160 mg once-daily doses of lurasidone significantly reduced the severity of depressive symptoms in patients with schizophrenia. Daily doses of 160 mg demonstrated the largest effect size. These results warrant further evaluation of lurasidone in patients with schizophrenia and co-morbid depression.