Critical appraisal of lurasidone in the management of schizophrenia

Lurasidone is a new atypical antipsychotic in the benzoisothiazoles class of chemicals. Like most second-generation antipsychotics it is a full antagonist at dopamine D(2) and serotonin 5-HT(2A) receptors, and is a partial agonist at 5-HT(1A) receptors, a property shared by some but not all older agents. It has much greater affinity for 5-HT(7) subtype receptors than other atypical antipsychotics. Pharmacokinetic studies showed that lurasidone is reasonably rapidly absorbed, with bioavailability appearing to be increased by food. Lurasidone undergoes extensive metabolism to a number of metabolites, some of which retain pharmacological activities. Metabolism is mainly by CYP3A4, resulting in steady-state concentrations that vary between individuals and are potentially affected by strong inducers and inhibitors of this enzyme. Short-term clinical trials have demonstrated the efficacy of lurasidone in acute schizophrenia, with doses of 40 and 80 mg/day giving significant improvements from baseline in the PANSS and BPRS scores. The most common adverse events are nausea, vomiting, akathisia, dizziness, and sedation, with minimal increases in the risk of developing metabolic syndrome. Lurasidone did not raise the risk of QTc interval prolongation, although additional studies are required. Long-term trials are also needed to assess the risk of new-onset diabetes. Ongoing trials in patients with bipolar disorder are being completed but, again, efficacy and safety have been investigated only in a few short-term clinical trials.