Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

Abstract

Background

Severe and persistent mental illnesses in children and adolescents, such as early- onset schizophrenia spectrum (EOSS) disorders and pediatric bipolar disorder (pedBP), are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.

Methods

PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.

Results

Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.

Conclusions

The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine-treated youth focused attention on the potential long-term risks of atypical antipsychotics in youth.

Keywords:

• early-onset schizophrenia
• pediatric bipolar disorder
• antipsychotic

Disclosures

Dr Maloney has received software for a computer intervention in schizophrenia from Posit Science. Dr Sikich receives research funding from NIMH, NIH, Foundation of Hope, Case Western Reserve University (subcontract from NICHD), NY Institute for Mental Hygiene Research (subcontract from NIMH), and Bristol Myers-Squibb. She is participating or has participated in clinical trials with Otsuka, Bristol Myers- Squibb, Neuropharm, Curemark, and Seaside Pharmaceuticals. She also received medication for clinical trials from Eli Lilly, Janssen, and Bristol Myers-Squibb, and software for a computer intervention in schizophrenia from Posit Science. She has served as a consultant for Sanofi Aventis within the past 2 years. She has given CME talks that have been indirectly supported by Bristol Myers-Squibb.