Treatment resistant psychosis in children and adolescents and clozapine: Nuances

With proliferation in research on high-risk psychosis spectrum diseases, it is crucial to distinguish a prodrome or psychosis-like episode in children and adolescents from true psychosis. The limited role of psychopharmacology in such circumstances is well-documented, underlining the difficulties in diagnosing treatment resistance. To add to the confusion is emerging data on the head-to-head comparison trials for treatment-resistant and treatment-refractory schizophrenia. Clozapine, the gold-standard drug for resistant schizophrenia and other psychotic psychopathology, lacks FDA or manufacturer guidelines for use in the pediatric population. Possibly due to developmental pharmacokinetic (PK) considerations, clozapine-related side effects are more commonly seen in children than adults. Despite evidence of an increased risk for seizures and hematological problems in children, clozapine is widely used off-label. Clozapine reduces the severity of resistant childhood schizophrenia, aggression, suicidality, and severe non-psychotic illness. There is inconsistent prescribing, administration, and monitoring of clozapine, and limited database evidence-backed guidelines. Despite the overwhelming efficacy, problems remain regarding unambiguous indications of use and risk-benefits assessments. This article reviews the nuances in the diagnosis of treatment resistance psychosis in childhood and adolescents and its management, in particular highlighting the evidence base for clozapine in this population group.