Tardive dyskinesia: reversible and irreversible.

The long-term prognosis of tardive dyskinesia (TD) has been insufficiently studied. Symptoms are reversible in many patients, but an irreversible course is widely believed to be the expected outcome. This pessimistic view has led to the assumption that neuroleptics should not be used in patients with TD because these drugs will produce an inevitable aggravation of TD. To clarify this issue, 27 patients were serially evaluated over 5 years for changes in neuroleptic treatment, TD, and mental status. Ten patients were able to discontinue medications; 15 required continued low-dose neuroleptic therapy [average 223 mg/day chlorpromazine (CPZ) equivalents], and two needed high doses (1000-2000 mg/day CPZ equivalents) to control psychosis. The majority of patients improved by more than 50% in both treated and untreated groups. In 8 of 27 patients (29.6%) TD resolved; in 1 patient TD increased by 25%. Younger patients improved the most. Prognosis was most favorable if neuroleptics were discontinued, but improvement was still possible with low to moderate doses (less than 600 mg/day CPZ equivalents). The large majority of patients with schizophrenia or schizoaffective illness relapsed, and required continued drug treatment. TD must be evaluated over several years to monitor the resolving/persisting course. Control of psychosis and improvement of TD during low-dose neuroleptic treatment suggest the antipsychotic and neurological effects of neuroleptics may involve different thresholds or mechanisms of action.