HALOPERIDOL AND ATTENTIONAL LEARNING IN AUTISTIC CHILDRE

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The aims of this application are two-fold: (1) To critically assess the efficacy and safety of naltrexone in the treatment of autism: its effects on behavioral symptoms and on learning. 40 children, ages 2 to 7 years, with DSM-III-R diagnoses of Autistic Disorder, Infantile Onset will be entered in a parallel groups design, double- blind placebo-controlled study of naltrexone lasting 6 weeks. Following a 2-week placebo baseline children will be randomly assigned to either naltrexone or placebo for 3 weeks followed by a final week on placebo. Dosage will range from 0.5 to 1.0 mg/kg/day; steady state plasma concentration of naltrexone will be related to clinical response, subjects will be rated by multiple raters on a variety of subjective and objective scales and will participate in an operant conditioning, learning discrimination task in an automated laboratory. This study is necessary to assess the effects of daily administration of naltrexone, a drug which has been effective in open, acute drug trails with autistic children. Alternative treatments to haloperidol, the most commonly used medication with autistic children who require pharmacotherapy, are sought because of the high incidence of neuroleptic-related dyskinesias. (2) We also wish to continue our long-term prospective study of haloperidol in autistic children: to assess its effects on behavioral symptoms, intellectual functioning, growth, stereotypes and drug-related dyskinesias. 30 new children will be enrolled and added to the sample. The design calls for an initial baseline assessment followed by 6 months on haloperidol and then 1 month on placebo. Children requiring further treatment with medication then begin another 7-month cycle. Autistic children belong to a population of patients who have high baseline rate of abnormal movements (stereotypies) unrelated to neuroleptic administration. Particularly in the area of mouth and tongue, it is difficult and at times impossible to differentiate stereotypies from neuroleptic (withdrawal) dyskinesias without a baseline assessment. A research question which is also of great clinical importance is to differentiate between these two types of movements. In our prospective study, each subject has a stable baseline assessment of stereotypies by multiple raters, on 3 rating scales and videotaping repeated at fixed times. Our study is unique in assessing the effects of long-term treatment of haloperidol and to clarify the occurrence, topography, and factors affecting the onset of neuroleptic-related dyskinesias, a major public health concern. We now have a large enough sample of carefully studied children to permit statistical analyses of the many measures collected over time.