Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial.
OBJECTIVE
Lurasidone is a novel psychotropic agent with high affinity for D(2) and 5-HT(2A) receptors, as well as for receptors implicated in the enhancement of cognition and mood and the reduction of negative symptoms (5-HT(7), 5-HT(1A), and alpha(2c)). The objective of the study was to evaluate the safety and efficacy of lurasidone in patients hospitalized for an acute exacerbation of DSM-IV-defined schizophrenia.


METHODS
Patients were randomly assigned to 6 weeks of double-blind treatment with a fixed dose of lurasidone 80 mg (N = 90, 75.6% male, mean age = 39.7 years, mean baseline score on the Brief Psychiatric Rating Scale derived from the Positive and Negative Syndrome Scale [BPRSd] = 55.1) or placebo (N = 90, 77.8% male, mean age = 41.9 years, mean BPRSd score = 56.1). The primary efficacy measure was the BPRSd. The study was conducted from May to December 2004.


RESULTS
At day 42, last-observation-carried-forward endpoint, treatment with lurasidone was associated with significant improvement compared to placebo on the BPRSd (least squares mean +/- SE = -8.9 +/- 1.3 vs. -4.2 +/- 1.4; p = .012), as well as on all secondary efficacy measures, including the PANSS total score (-14.1 +/- 2.1 vs. -5.5 +/- 2.2; p = .004) and the PANSS positive (-4.3 +/- 0.7 vs. -1.7 +/- 0.7; p = .006), negative (-2.9 +/- 0.5 vs. -1.3 +/- 0.5; p = .025), and general psychopathology (-7.0 +/- 1.1 vs. -2.7 +/- 1.2; p = .0061) subscales. Significant improvement was seen as early as day 3, based on BPRSd, PANSS, and Clinical Global Impressions-Severity of Illness assessments. Treatment with lurasidone was generally well tolerated and was not associated with adverse changes in metabolic or electrocardiogram parameters. There were no clinically significant differences between lurasidone and placebo in objective measures of extrapyramidal symptoms.


CONCLUSIONS
The results of this study suggest that the novel psychotropic agent lurasidone is a safe and effective treatment for patients with an acute exacerbation of schizophrenia.


BACKGROUND
(ClinicalTrials.gov) Identifier: NCT00088634.
Nakamura
Mitsutaka
M
Dainippon Sumitomo Pharma America Inc, Fort Lee, NJ 07024, USA.
Ogasa
Masaaki
M
Guarino
John
J
Phillips
Debra
D
Severs
Joseph
J
Cucchiaro
Josephine
J
Loebel
Antony
A
D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054833:Isoindoles / Q000009:adverse effects / Q000627:therapeutic use*; D000069056:Lurasidone Hydrochloride; D008297:Male; D008875:Middle Aged; D011594:Psychometrics; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D054833:Isoindoles; D013844:Thiazoles; D000069056:Lurasidone Hydrochloride