Comment on the Potential Utility of the New Atypical Antipsychotic Lurasidone in the Geriatric Population

Abstract

Lurasidone is the tenth atypical antipsychotic to be marketed in the United States. Like other atypical agents, lurasidone binds to a variety of central nervous system receptors, including dopamine (D2), norepinephrine (alpha 2A and 2C), and serotonin (1A, 2A, and 7) receptors. At these receptors, the drug acts as an antagonist except at serotonin 1A receptors, where it is a partial agonist. It behaves like an antipsychotic agent in animal models predictive of such activity. In addition, it behaves as a cognition enhancer in animal models of learning and memory impairment. In vivo in humans, lurasidone has been effective in significantly improving the positive and negative symptoms of schizophrenia in young adults as well as demonstrating preliminary positive effects on cognition in this population. The bioavailability of lurasidone is enhanced three-fold by administration with food. It is virtually completely metabolized, the major exo-hydroxy metabolite exhibiting the same pharmacology as the parent compound. Despite this, renal and hepatic impairment substantially affect the drug's pharmacokinetics, necessitating dose reduction or limitation. Several metabolic drug-drug interactions are clinically important (CYP450 isozyme 3A4-based). Lurasidone will be a difficult drug to use in the elder patient population because of the virtual absence of elder-specific information, limitations of existing formulations (40 and 80 mg nonscored tablets) in enabling precise dosage adjustment, and the substantial difference in bioavailability with food versus fasting, with attendant risks for over- and underdosing depending on when the drug is ingested. It would be prudent to avoid using this agent until relevant geriatric-specific data are published.