Clozapine is a unique antipsychotic with superior efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, approximately 40% to 70% of patients on clozapine continue to experience psychotic symptoms. Nevertheless, there is a concern about how high of a dose to prescribe because adverse effects are related to plasma levels of the drug. In this podcast, Dr. Jan Bogers discusses his research involving stepwise increases in clozapine doses in severely ill, long-stay patients with TRS. The study, conducted at Rivierduinen Mental Health Organization in the Netherlands, concludes that most patients older than 60 years could not tolerate high clozapine levels and so this should not be attempted in older or otherwise physically vulnerable patients. Increasing clozapine levels to approximately 750 ng/mL in middle-aged patients with longstanding TRS may modestly reduce the severity of positive symptoms and improve the response rate. The article appears in the March-April 2023 issue of the Journal of Clinical Psychopharmacology.