Clinically Useful Approaches for the Atypical Antipsychotics (Second Generation Antipsychotics) in Pediatric Psychotic Disorders

Abstract

Atypical antipsychotics, which include clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon) are approved by the U.S. Food and Drug Administration (FDA) for adults with bipolar disorder and schizophrenia. However, currently, no atypical antipsychotic has been approved by the FDA for use in children and adolescents. Nonetheless, clinicians frequently prescribe these medications for children and adolescents since they have lower rates of side effects than conventional antipsychotics. Although these medications can treat a broad range of psychiatric disorders in childhood, we will focus on the treatment of pediatric psychotic disorders such schizophrenia, schizoaffective disorder, psychotic mood disorders, psychosis due to a medical condition, and psychosis not otherwise specified (NOS). Children and adolescents are often initially diagnosed with psychosis NOS since there may be evidence of psychotic symptoms but they do not meet the threshold for another DSM–IV psychotic disorder. Additionally, in new onset psychosis, it can be difficult to uncover the primary illness since developmental issues, such as multiple co–occurring diagnoses and age–specific manifestations of psychotic disorders complicate diagnosis. Indeed, studies have shown that there is frequently a three year delay prior to treatment for the first episode of psychosis in children and adolescents. However, early treatment may be important in preventing neurotoxicity. Therefore, clinicians need to feel comfortable with using atypical antipsychotics for psychotic disorders in pediatric patients. The goal of this review is to discuss possible side effects, the management and monitoring of adverse effects, and typical dosing of atypical antipsychotics in the treatment of psychotic disorders in children and adolescents. Although there has been evidence for the efficacy and effectiveness of atypical antipsychotics in children and adolescents, there have been few controlled studies. In a 6–week double–blind comparison of clozapine and haloperidol for childhood–onset schizophrenia (N = 21, mean age = 14), clozapine was found to be more efficacious for positive and negative symptoms. Risperidone has also been found to be efficacious for pediatric psychosis in case reports, retrospective reviews, and open–label prospective studies (age: 6–18, dose: 0.5 mg–10 mg/day). Seven open–label studies (N > 100) have suggested that olanzapine may be efficacious for pediatric psychosis (age: 6–18, dose: 2.5 mg–20 mg/day). In a double–blind parallel study of risperidone, olanzapine, and haloperidol (Sikich et al, 2004) for psychosis in adolescents (N = 50, age range = 8–19, mean age = 15), risperidone (0.5 mg–3 mg, max = 6 mg) and olanzapine (2.5 mg–12.5 mg, max = 20 mg) had superior efficacy as compared to haloperidol (1 mg–5 mg, max = 8 mg). There have been case reports and two open label studies that have suggested that quetiapine may be efficacious for the treatment of psychosis in adolescents (dose = 400 mg BID, age range = 12–16). To our knowledge, there has been no published data on the use of aripiprazole or ziprasidone for psychosis in children and adolescents. Adverse Effects of Second Generation Antipsychotics (SGAs)