Levodopa and receptor sensitivity modification in tardive dyskinesia

Tardive dyskinesia (TD), a syndrome of involuntary hyperkinetic movements, purportedly involves the development of dopamine (DA) receptor hypersensitivity following long-term receptor blockade with neuroleptic drugs. It has been proposed that through a process of receptor hypersensitivity modification, TD can be treated by reversing the receptor hypersensitivity with DA agonists. Thirteen patients with TD were treated for 4--8 weeks with levodopa plus benserazide, a peripheral decarboxylase inhibitor (Madopar, Roche, Basel, Switzerland) over a wide dose range corresponding to 3.0--9.0 g/day levodopa. Drug effects was assessed by blind evaluations of randomly sequenced videotapes made before, during, and for 6 weeks following treatment. TD scores moderately increased during levodopa. After the drug was discontinued, TD scores returned to pretreatment baseline levels without further improvement in those patients receiving concurrent neuroleptic medications (N = 9), but in the neuroleptic-free patient TD scores decreased 25% in three patients and were resolved in one younger patient. Psychological effects of depression or increased psychotic symptoms occurred at higher drug doses. These results do not support the proposal that receptor sensitivity modification with levodopa is an effective therapeutic approach to TD, though selected patient and drug treatment variables, including other DA agonists, are considerations for further investigation.