Tardive dyskinesia: An update

Tardive dyskinesia (TD) is a serious motor side effect of chronic neurolept ic therapy. TD is a complex hyperkinetic syndrome consisting of choreiform, athetoid or rhythmic abnormal involuntary movements. The face, mouth and t ongue are most frequently involved (orofacial type), but a variety of less frequent motor abnormalities of the upper and lower limbs and of the trunk may also occur. TD usually has a delayed onset and the intensity of the syn drome may fluctuate over time. The most serious aspect of TD is that it may persist for months or years after drug withdrawal and in some patients is irreversible. In spite of the prevalence and known etiology that chronic ne uroleptic treatment causes TD, relatively little is known about the primary pathological mechanism underlying the condition. Abnormalities in various neurotransmitter systems have been implicated in the pathophysiology of TD, including the dopaminergic, GABAergic, serotonergic and noradrenergic syst ems. Recently, excitotoxicity of the glutamatergic system and oxidative str ess have received much attention. Three general types of animal models have contributed to our knowledge of TD and can be described as homologous, ana logous and correlational models. There are no empirically validated guideli nes to follow when choosing a suppressive agent. In general, therapeutic tr ials have attempted to manipulate the dopaminergic, GABAergic, serotonergic and noradrenergic systems, in part due to theories on the pathophysiology of TD. None of these medications has proven successful in the majority of p atients. Much more research is needed in order to increase our understandin g of TD and to develop better therapeutics for its treatment. (C) 2001 Prou s Science. All rights reserved.