Iloperidone, asenapine and lurasidone: a primer on their current status

INTRODUCTION: Three newer atypical antipsychotic drugs were FDA-approved in 2009 and 2010 in the following order: iloperidone, asenapine and lurasidone. The three drugs are indicated for the treatment of acute schizophrenia. Asenapine is also approved for treatment of manic or mixed episodes associated with bipolar I disorder, for the maintenance treatment of schizophrenia and as an adjunctive therapy with lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. AREAS COVERED: This review compares and contrasts the current preclinical, clinical, safety and tolerability profiles of the three newer drugs, as reported in published preclinical and clinical studies, product labels, poster presentations and press releases. EXPERT OPINION: Preclinical studies have reported that the three drugs have variable affinities for a wide range of neurotransmitter receptors, and are active in animal models predictive of antipsychotic activity. Asenapine is the first antipsychotic to be administered sublingually, whereas iloperidone requires titration to minimize orthostatic hypotension. Asenapine and lurasidone are associated with dose-related akathisia, whereas iloperidone is not. The three drugs appear to have relatively benign metabolic profiles. The availability of the three novel antipsychotics should provide additional options for improved treatment of schizophrenia and other psychotic disorders.