Neuroleptic plasma levels and tardive dyskinesia: a possible link?

Tardive dyskinesia is known to appear or worsen with the reduction or discontinuation of neuroleptic treatment. The onset of tardive dyskinesia in chronically medicated schizophrenic patients may be related to a gradual decline in neuroleptic plasma concentrations after years of treatment, probably due to increased metabolism of the drug as well as other factors in chronic neuroleptic treatment that may result in lowering of plasma concentrations. Dopamine receptor hypersensitivity could gradually develop and increase, and dyskinetic symptoms eventually appear clinically, as if the dose had been reduced. The symptoms are usually suppressed by increasing the neuroleptic dose which would result in higher plasma drug concentrations. Supportive evidence for this hypothesis is presented and discussed.