Clinical trials of D1 and D2 dopamine modulating drugs and self‐injury in mental retardation and developmental disability

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Abstract
We review the rationale for conducting clinical trials of D1 and D2 dopamine modulators for self‐injurious behavior (SIB) among people with mental retardation and developmental disabilities. We include a brief history of the relevant behavioral research on SIB, the psychopharmacology of neuroleptic drugs for SIB, pharmacotherapy for SIB based on dopamine function, treatment for SIB with neuroleptics, SIB and dopamine supersensitivity, and the D1 dopamine hypothesis and SIB. We also present controlled case studies of the use of clozapine to treat chronic, refractory SIB in three individuals with profound mental retardation. One was a dramatic responder at 225 mg per day; one was a partial responder at 300 mg per day; and one showed a decrease in stereotypy, but not SIB, at 100 mg per day. Studies from rats, monkeys, and humans support the hypothesis that the D1 dopamine receptor system in the nigrostriatal pathway of the basal ganglia plays a key role in SIB in some cases.