This narrative review provides an overview of the three new oral second-generation antipsychotics that have become available in the US: iloperidone, asenapine and lurasidone. Although they are associated with less weight gain and fewer metabolic abnormalities than some of the older second-generation antipsychotics, iloperidone, asenapine and lurasidone have differences that make them unique from each other. Examples of these differences include dosing frequency, specific instructions on dosing with food, titration requirements, and potential association with sedation, extrapyramidal side effects, akathisia, and prolongation of the ECG QT interval. Additional information is provided regarding agents in late stage clinical development for the treatment of schizophrenia: cariprazine and brexpiprazole (both are dopamine D2 receptor partial agonists) and bitopertin (a glycine transport inhibitor that may have antipsychotic effects).

Antipsychotics are the mainstay of treatment for patients with schizophrenia. However, these medications only work if they are taken and perhaps work best if they are taken for longer periods of time than seen in typical research trials. Here we explore the idea of “time as a drug” by reviewing the data showing the potential benefits of long-term antipsychotic use. We also discuss the utility of depot antipsychotic formulations for improving the chances of attaining long-term therapeutic results.