Atypical Neuroleptic Drugs in People With Mental Retardation/Developmental Delay
Atypical Neuroleptic Drugs in People With Mental Retardation/Developmental Delay
Psychiatric drugs are often used to treat behavioral symptoms of mental
 retardation/developmental delay (MR/DD). These drugs can cause serious side effects. Newer
 drugs may have decreased side effects. This study will compare new and old drugs used to
 treat behavioral symptoms in people with MR/DD.
Atypical neuroleptics have fewer extrapyramidal and behavioral side effects than typical
 neuroleptics. Atypical neuroleptics may also improve social and cognitive functioning. This
 improvement may be due to reductions in the negative symptoms that are part of the psychosis
 and psychiatric syndromes or to the improved side effect profile. This study will examine the
 effects of the atypical neuroleptic drugs risperidone, clozapine, and olanzapine on learning,
 memory, and social behavior in individuals with MR/DD. A substudy will expand the study to
 evaluate ecobehavioral measures. The goal of these studies is to assess the behavioral
 selectivity of atypical neuroleptics by measuring cognitive and social functioning along with
 targeted aberrant behaviors in individuals under placebo and different doses of drug.

 Fifty participants will be randomized to receive risperidone, clozapine, olanzapine, or
 placebo. Twenty-five of the participants will be drawn from a group receiving typical
 neuroleptics at the onset of the study. The efficacy of atypical neuroleptics in reducing
 destructive, aggressive, and stereotypic behaviors in persons with mental retardation will be
 assessed.

 Learning and memory will be measured using laboratory operant tasks. Social and environmental
 interactions, as well as primary target behaviors, will be directly measured by trained
 observers. The frequency of specific aberrant behaviors will be determined, along with the
 conditional probabilities that certain environmental events proceed and follow these
 behaviors. In the substudy, categories of aberrant behavior will be used to provide
 information relevant to environmental variables maintaining aberrant behavior; this
 categorization will improve the determinations of pharmacologic efficacy and will provide a
 better understanding of the relationship between atypical neuroleptics and environmentally
 maintained aberrant behavior.
Inclusion Criteria

 -  Primary diagnosis of mental retardation (IQ < 70)

 -  Scheduled for medication reductions from psychotropic drugs and subsequent placement
 on risperidone

 -  Severe self-injury, aggression, property destruction, or stereotypic behavior for 6
 months prior to study entry

 -  No seizures, or seizures under control of medication for previous 2 years

 Additional Inclusion Criteria for Substudy

 -  Participants in the primary study who are available for 2 hour weekly or bi-weekly
 clinic visits and are able to have observers in their home, school, and/or work
 environment

 Exclusion Criteria

 -  Degenerative disease that may affect motor or cognitive functioning

 -  Progressive disease of an organ system

 -  Advanced age that may produce deteriorating cognitive or motor functioning

 -  Multiple sensory or motor disabilities that will interfere with seeing the stimuli and
 responding to the computer