In Strategic Plan 2000, the National Institute of Child Health & Human Development (NICHD) outlines its public health mission of investigating the understudied area of pharmacologic treatments in developmental disabilities, particularly the long-term safety of commonly used drugs. In line with this mission, the aim of the proposed study is to critically assess both the short-term and long-term safety and efficacy of olanzapine in children with autistic disorder. Atypical neuroleptics, including olanzapine, have been increasingly used to treat children. A study conducted at a Specialty Clinic established by the Principal Investigator suggests that olanzapine may be a safe and effective treatment in this population. Since our original application to the NICHD, we have been funded by the FDA to conduct a significant portion of the short-term phase of the study proposed herein. Therefore, with less support than originally proposed, we will be able to extend the FDA study to include our aim of investigating the long-term safety and efficacy of olanzapine treatment in children with autism. Autistic disorder is a severe disorder of early childhood and affects most areas of development. While mainstay treatments include educational and psychosocial approaches, pharmacotherapy is often required to decrease symptoms that interfere with learning and daily functioning. The conventional neuroleptic, haloperidol, and the atypical agent, risperidone, are the most critically assessed drugs in this population. However, long-term administration is limited by untoward effects, including tardive dyskinesia. Olanzapine may be effective and have safety advantages over these agents, namely, less risk for extrapyramidal effects including dyskinesias. However, there are no completed placebo-controlled trials of olanzapine in children with autistic disorder (or any other childhood disorder). The proposed study is particularly important because it investigates the long-term safety and efficacy of olanzapine; such studies are rare in children. The subjects will be 78 children, aged 4 to 12 years, diagnosed with autistic disorder (DSM-IV). The study has 3 phases. Phase 1 is a short-term (6 weeks) double-blind and placebo controlled comparison of olanzapine and placebo, using parallel groups design and randomization to treatments. Phase 2 is a long-term (6 months) maintenance study of olanzapine responders who continue on open-labeled treatment. Phase 3 is a naturalistic follow-up of subjects. Multiple measures and raters are employed.
| Malone, Richard P; Harvey, John A (2008) Abnormal movements with the addition of clindamycin to risperidone in a girl with autism. J Child Adolesc Psychopharmacol 18:221-2 |
| Malone, Richard P; Gratz, Silvia S; Delaney, Mary Anne et al. (2005) Advances in drug treatments for children and adolescents with autism and other pervasive developmental disorders. CNS Drugs 19:923-34 |
