Treatment-refractory schizophrenia in children and adolescents: an update on clozapine and other pharmacologic interventions.

Treatment-refractory early-onset schizophrenia is a rare but severe form of the disorder associated with poor premorbid function and long-term disability. The currently available evidence suggests that clozapine remains the most efficacious treatment for the amelioration of both positive and negative symptoms of the disorder and problematic aggressive behaviors. Clozapine use in children and adolescents, however, is limited by its association with hematologic adverse events and an increased frequency of seizure activity. Further studies are needed to examine the usefulness of antipsychotic combinations and of augmentation therapies to antipsychotic medications in order to treat persistent residual psychotic symptoms in children and adolescents who have schizophrenia and who have not responded to several sequential trials of antipsychotic monotherapy.