Tardive dyskinesia

Abstract

Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression.

Adenosine A_2A-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

“…The postsynaptic dopamine-receptor hypersensitivity hypothesis suggests that long-term dopamine-receptor blockade by antipsychotics, which is clinically associated with parkinsonism, results in adaptive phenomena that increase the sensitivity to dopamine agonists [36]. The hypersensitivity hypothesis is supported by the observations that tardive dyskinesia is associated with chronic dopamine-receptor blockade and that increasing dopaminergic blockade suppresses tardive dyskinesia [33,36].…”

Les effets des neuroleptiques et la recherche sociale en psychopharmacologie

“…Chez les patients âgés institutionnalisés, le taux de prévalence atteint les 40 poui cent (Yassa et al, 1988). On considère aujourd'hui que si les symptômes sont reconnus tôt et si l'on ;esse le traitement, la DT peut s'améliorer ou éventuel-lement disparaître dans une minorité des cas i Gerlach et Casey, 1988 ;voir aussi Shriqui, 1988, pour une excellente mise à jour en français sur la DT). Pour la majorité des patients atteints, la DT semble irréversible: l'étude récente de Bergen et al (1989), portant sur 101 patients avec DT persistante évalués à quatre ans d'intervalle, rapporte un taux d'amélioration chez neuf patients, une aggravation chez huit, et aucun changement chez 83 patients.…”

“…Tous les neuroleptiques, considérés comme indispensables dans la gestion du comportement psychotique, ont le potentiel de générer des symptômes extrapyramidaux, dont la dyskinésie tardive (DT), trouble neurologique persistant qui se manifeste par des mouvements involontaires, anormaux et continuels du visage, du tronc ou des extré-mités dont sont atteints un cinquième des patients psychiatriques chroniques (Gerlach et Casey, 1988). Le nombre de personnes atteintes de DT est difficile à établir, bien que ce désordre iatrogénique fut décrit pour la première fois à la fin des années 50.…”

The relevance of recent advances in psychopharmacology for social psychiatry

“…This portion of the patients places disproportionate strains on the community psychiatric services and leads to frequent, short but largely ineffectual hospital admissions and poor quality of life (Awad et al, 1995). A further problem involved the high incidence of unpleasant and even severe unwanted effects of typical antipsychotic drugs, including long term effects such as tardive dyskinesia (Gerlach & Casey, 1988). The increased availability of clozapine around 1990 was hailed in the USA and some European countries as the needed breakthrough.…”