Beyond the Off-Label: A Systematic Review of What We Know About Clozapine Use for Children

Introduction: It is essential not to delay behavior management and control for aggression, violence, and impulsive behavior in young people. Clozapine has been widely used in adolescents and adults to manage violence and aggression in Schizophrenia. However, there are limited data on the use of clozapine in children, and no systematic review has addressed its use in this population. Objective and Methods: To better understand the conditions under which clozapine is used as a therapeutic alternative for nonschizophrenic diagnoses and to assess the current evidence supporting its prescription to children, a systematic review was conducted. The review followed PRISMA guidelines and was registered in PROSPERO under the ID CRD42024537707. Results: The review identified that all the studies used clozapine to address externalizing behavior, particularly aggressive behavior, and found positive outcomes supporting its use for treating children with treatment-resistant aggression. The studies also found that clozapine was well-tolerated in all cases. However, the studies were limited and mainly consisted of open trials without a control group. Conclusion: Further high-quality research is needed to establish precise guidelines for using clozapine in children.