Available data although limited in terms of number of studies are consistent in demonstrating that CLZ is effective and generally safe in the treatment of refractory EOS provided patients are regularly monitored.

Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS.

Antipsychotic medications (APs) are a well-established pharmacological treatment in adults with serious mental health problems. However, many adult mental health disorders have their origins and onset in childhood or adolescence. The understanding that neuropsychiatric conditions of childhood are in part biologically determined, led to an increase in the number of clinical trials supporting evidence on the efficacy of antipsychotic agents as first-line treatment for childhood psychotic disorders and therapeutic augmentation of nonpsychotic conditions. In recent years the use of antipsychotics in children and adolescents for neurodevelopmental, behavioural and psychiatric disorders has significantly increased while the age of prescription has decreased. These trends have not been matched by advances in the understanding of APs' safety profile in this group of patients. It is therefore crucial that current and future practice is informed by up-to-date synthesis of the evidence and clinical guidelines about the use and monitoring of these treatments in paediatric populations, since the effectiveness of early therapeutic interventions in children can affect positively the long-term outcome.

The spectrum of the possible manifestations of Langerhans' cell histiocytosis in children is very wide, ranging from a simple rash to major multiorgan disease. There may be hypothalamic and pituitary dysfunction or more global neurological and neuropsychiatric manifestations when the central nervous system is affected. The cerebellum is preferentially affected for yet undetermined reasons. The clinical presentation includes motor dysfunction as well as cognitive, behavioral, and psychiatric expression of the ongoing neurodegeneration. We report a young patient with Langerhans' cell histiocytosis who underwent an unusual course of psychiatric deterioration.