Improving Adherence and Outcomes in Early Onset Schizophrenia: A Case Series on Role of Clozapine and Long-Acting Injectables for Refractory Courses

Early onset schizophrenia (EOS) is a rare and severe psychiatric disorder associated with marked functional impairment and a complex diagnostic trajectory. Comorbid anxiety, mood dysregulation, and substance use further complicate clinical presentation and contribute to a more refractory course. Clozapine is widely acknowledged as the most efficacious treatment for individuals unresponsive to conventional antipsychotic therapy. However, its use in adolescents remains limited despite strong evidence of substantial clinical benefits, given the insidious and pernicious nature of this disorder. Although formal trials in adolescents are limited, observational data and clinical practice suggest that this combined approach may offer meaningful advantages for youth with persistent psychosis. This case series describes six adolescents between 15 and 17 years of age who presented with severe psychotic symptoms, recurrent aggression, suicidality, or significant functional decline despite multiple adequate trials of oral antipsychotic medications. Clozapine was initiated in each case, and four patients also received a long-acting injectable antipsychotic (LAI) after establishing oral tolerability. Across cases, clozapine alone or in combination with an LAI was associated with substantial improvement in positive symptoms, behavioral regulation, and overall clinical stability, allowing transition to the least restrictive settings. These findings illustrate the potential usefulness of clozapine and clozapine combined with LAI medications in adolescents with treatment-resistant EOS. They highlight the importance of early consideration of clozapine within a comprehensive treatment framework and point out the need for rigorous prospective research to guide clinical practice.