Tardive dyskinesia: natural history studies assist the pursuit of preventive therapies.

Contemporary thinking about tardive dyskinesia is undergoing a quiet revolution. In the fourth decade following the introduction of neuroleptic medications for the treatment of schizophrenia, tardive dyskinesia research has moved from debates over its very existence to careful, scholarly sub-typing of clinical variants. Investigators are also beginning to elucidate the epidemiology and natural history of tardive dyskinesia as a proper disease. These present-day research endeavours are setting the stage for what we all hope will be the next era of research in this field: namely, treatment and prevention. If the pre-eminent challenge in the field of tardive dyskinesia research is to discover an antipsychotic drug which does not cause tardive dyskinesia, why are investigators interested in the natural history of tardive dyskinesia? One of the major reasons is the need for a strategy whereby the presence or absence of acute drug effects could be predictive of chronic drug effects (Stahl, 1985). That is, can we be confident that a new antipsychotic drug without the acute side-effects of akathisia or Parkinsonism will also not cause the chronic side-effect of tardive dyskinesia? Only upon completion of careful prospective studies of the natural history of acute neuroleptic side-effects merging with chronic neuroleptic side-effects, superimposed upon the natural history of schizophrenia, will we be able to generate with any confidence a clinical research strategy for antipsychotic drugs which do not produce tardive dyskinesia.