Tardive dyskinesia is an involuntary movement disorder common in a subpopulation of psychiatric patients who have received chronic treatment with neuroleptics. This project aims to develop a treatment strategy for tardive dyskinesia (TD) using the dopamine (DA) agonist Sinemet (L-DOPA/carbidopa). The theoretical grounds for this approach is that the neuropathological defect in TD relates to the development of supersensitive dopamine receptors, and that stimulation with highdoses of DA agonists result in a normalization of their sensitivity to endogenously released DA. In addition, we will attempt to assess whether this treatment strategy does indeed change dopamine receptor sensitivity. In a randomly assigned, double-blind, placebo-controlled, rising-dose, crossover design, we will treat dyskinetic patients who have been neuroleptic-free for at least 1 month with Sinemet (L-DOPA/carbidopa) for four weeks. Both live and videotaped sessions will be used to monitor changes in dyskinetic symptoms. Patients will be challenged with amphetamine at critical intervals during the protocol to determine the degree to which covert dyskinetic symptoms can be elicited 1) when 4-week's neuroleptic free, 2) after treatment with placebo, and 3) after treatment with L-DOPA. In addition to the TD assessments, changes in degree of psychosis and plasma growth hormone (GH) and prolactin (PRL) levels will be monitored during these amphetamine challenges. These measures will be used to determine whether supersensitivity of DA receptors is observed in other CNS dopaminergic systems after chronic neuroleptization and whether their responsivity to stimulation normalizes after L-DOPA treatment.
