Lurasidone: An Atypical Antipsychotic for Schizophrenia

OBJECTIVE: To provide a clinical overview of the antipsychotic lurasidone. DATA SOURCES: Articles were identified by searching the MEDLINE, PubMed, Cochrane Library, and EBSCO databases (through February 2012) using the key word lurasidone. The manufacturer provided information on unpublished Phase 2 and 3 trials. The Clinicaltrials.gov database was reviewed for the status of ongoing and upcoming trials. STUDY SELECTION AND DATA EXTRACTION: All clinical trials lasting longer than 3 weeks and published in the English language were selected for review. Additional documentation, including the product dossier, package insert, and poster presentations supplied by the publisher, was also evaluated. DATA SYNTHESIS: Lurasidone hydrochloride is an atypical antipsychotic that is approved for the treatment of schizophrenia. It is under investigation for treatment of bipolar I disorder. It should be administered with food, is pregnancy category B, is contraindicated for coadministration with strong CYP3A4 inducers and inhibitors, and requires dose adjustments with certain medications and in renal and hepatic impairment. Like other atypical antipsychotics, lurasidone possesses dopamine D(2) and serotonin 5-HT(2A) antagonism but exhibits little affinity for histamine H(1), α(1)-adrenergic, or cholinergic M1 receptors. Additionally, it is a potent 5-HT(7) antagonist, which may impact depression and cognition. Phase 3 trial results revealed that 40-80 mg administered once daily resulted in statistically significant improvements in schizophrenia symptomatology compared with placebo. Lurasidone's rate of metabolic adverse events is low relative to other atypical antipsychotics; however, this is offset by dose-dependent increases in somnolence, akathisia, and parkinsonism. CONCLUSIONS: Lurasidone has shown efficacy when compared to placebo in acute schizophrenia. Full characterization of the adverse effect profile and cognitive and affective benefits requires publication of trials with longer durations.