Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies

CNS Spectr. 2015 Apr;20(2):140-7. doi: 10.1017/S1092852914000285. Epub 2014 Jun 23.

Abstract

Objective: Depressive symptoms are common in schizophrenia and can worsen outcomes and increase suicide risk. Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia and for the treatment of major depressive episodes associated with bipolar I disorder. This post hoc analysis evaluated the effect of lurasidone on depressive symptoms in patients with schizophrenia.

Methods: Patient-level data were pooled from 4 similarly designed, double-blind, placebo-controlled, 6-week registration studies of lurasidone (40-160 mg/d) in adult patients with an acute exacerbation of schizophrenia. Changes in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), were analyzed for the overall sample and for subgroups of patients stratified by baseline MADRS scores.

Results: MADRS assessments at baseline and endpoint (day 42 or last observation carried forward [LOCF]) were available for 1330 patients. Patients receiving lurasidone experienced significantly greater decreases in MADRS score (-2.8, least-squares [LS] mean change, LOCF) compared with patients receiving placebo (-1.4, P < .001, effect size 0.24). Analysis of change in MADRS score (LOCF) by baseline symptom severity (MADRS score of ≥12, ≥14, ≥16, ≥18) showed significantly greater improvement for lurasidone-treated patients across all severity groups; effect sizes ranged from 0.25 to 0.34. Among patients with a baseline MADRS score of ≥12, depressive symptom remission (defined as MADRS score <10 at LOCF endpoint) was attained by 45.0% of lurasidone-treated patients and 36.3% of patients receiving placebo (P < .05).

Conclusions: In a pooled analysis of short-term, placebo-controlled studies, lurasidone significantly improved depressive symptoms in patients with schizophrenia.

Trial registration: ClinicalTrials.gov NCT00088634 NCT00549718 NCT00615433 NCT00790192.

Keywords: schizophrenia.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / etiology*
  • Double-Blind Method
  • Female
  • Humans
  • Isoindoles / therapeutic use*
  • Lurasidone Hydrochloride
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Schizophrenia / complications*
  • Thiazoles / therapeutic use*
  • Young Adult

Substances

  • Antipsychotic Agents
  • Isoindoles
  • Thiazoles
  • Lurasidone Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00088634
  • ClinicalTrials.gov/NCT00549718
  • ClinicalTrials.gov/NCT00615433
  • ClinicalTrials.gov/NCT00790192