A major clinical problem in mentallly retarded children and adults is stereotyped behavior. Stereotyped behavior includes repetitive invariant topographic mannerisms, such as body rocking, head weaving, etc. Thioridazine (Mellaril ) is a phenothiazine antipsychotic drug that is the most frequently used psychtropic medication for control of behavior problems in retarded persons, including sterotypies. Despite its wide spread use, a number of questions remain concerning thioridazine's efficacy and the sequalae of its long term administration. This proposal will investigate how thioridazine affects the stereotypies in institutionalized mentally retarded persons. One study will investigate the effect of thioridazine withdrawal in clients who have been maintained on the drug and who are scheduled to be withdrawn. This experiment will also determine how environmental challenges affect withdrawal emergent symptons. A second study will examine the effects of both acute and chronic administration of thioridazine on stereotyped movements, including their rhythmical properties. A third study will investigate the interaction of pharmacotherapy with behavior management procedures. Data are presented to show that the actions of thioradazine may be due primarily to metabolites rather than the parent compound. A major strength of these studies are planned that will parallel the clinical studies. The animal studies will be done in hamsters, rather than rats, as preliminary data demonstrate that hamsters metabolize theoridazine in a way similar to that seen in humans. Thus, hamsters should provide a better model for pharmacodynamic studies with thioridazine. Chronic and acute drug effects, in combination with testing for effects of environmental challenges during withdrawal, will provide important animal data relevant to the interpretation of the clinical studies.
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