INCIDENCE AND CORRELATES OF TARDIVE-DYSKINESIA IN FIRST EPISODE OF SCHIZOPHRENIA

Background: There is controversy over whether tardive dyskinesia (TD) is solely a consequence of antipsychotic drug treatment or in part may reflect an intrinsic aspect of the disease process. Pathophysiologic factors could, independently or in concert with drug effects, lead to the development of dyskinetic signs. Methods: We studied prospectively 118 patients in their first episode of psychosis who were treatment-n aive or had less than 12 weeks of antipsychotic drug exposure at study entry. Patients received standardized antipsychotic drug treatment an d were evaluated for up to 81/2 years with regular assessments of psyc hopathologic signs and symptoms and side effects. Results: The cumulat ive incidence of presumptive TD was 6.3% after 1 year of follow-up, 11 .5% after 2 years, 13.7% after 3 years, and 17.5% after 4 years. Persi stent TD had a cumulative incidence of 4.8% after 1 year, 7.2% after 2 years, and 15.6% after 4 years. Taken individually, both antipsychoti c drug dose, entered as a time-dependent covariate, and poor response to treatment of the first psychotic episode were significant predicter s of time to TD. When antipsychotic drug dose and treatment response w ere examined together, treatment responders had significantly lower ha zards for presumptive TD than nonresponders (hazard ratio, 0.29; 95% c onfidence interval, 0.09 to 0.97). Dose was a trend-level predicter, w ith each 100-mg chlorpromazine equivalent unit increase in dose associ ated with a 5% increase in the hazard of presumptive TD (hazard ratio, 1.05; 95% confidence interval, 0.99 to 1.11). Conclusion: Poor respon se to the treatment of a first episode of psychosis and, to a lesser e xtent, antipsychotic drug dose are important factors in the developmen t of TD. This suggests that there may be a disease-related vulnerabili ty to TD manifest with antipsychotic drug exposure. Potential pathophy siologic factors might include neurodevelopmentally induced structural neuropathologic characteristics, sensitization of nigrostriatal dopam ine neurons, and the induction of glutamatergically mediated neurotoxi c effects.