Smoking and risk for tardive dyskinesia

Tardive dyskinesia l iD) is a frequent side-effect of treatment with neuroleptic chugs. The syndrome is persistent and is often irreversible. TD is characterized by orofacial dyskinesias, choreic movements and dystonias. Prevalence is on the order of ! 5-25% of patients treated with neuroleptics, with markedly increased risk associated with aging. Between 400,000 and a million Americans have TD. Public health aspects of TD include its impact on morbidity, quality of life and costs of health care. TD leads to increased rates of relapse and re-hospitalization, it prolongs hospital length of stay, and it may adversely affect the long term course of schizophrenia. Patients with TD are less likely to receive rehabilitation and resocialization and are less likely to find gainful employment. Direct costs associated with "rD include prolongation of hospitalization; costs of increased frequency of outpatient visits, costs ofclozapine, increased dental costs, medical workup costs and costs associated with lawsuits. There is no established treatment. Based on preliminary studies, initially by Lohr et al (2), and Adler et al. (3), and others (reviewed in (3)), we have planned a VA Cooperative Study to assess the efficacy and safety of vitamin E in treating TD. The Cooperative Studies format was chosen for a number of reasons. First, TD is a significant VA public health concern, it is an iatrogenie disorder affecting large numbers of patients with diverse primary illnesses; these patients have varying degrees of TD severity, and varying degrees of TD related impairment. For many of these patients reduction in TD severity would result in real and meaningful quality of life and economic gains. Second, in order to establish with a reasonable degree of certainty whether vitamin E has true efficacy, and to identify clinical characteristics predicting efficacy, a larger scale multicenter study, that could not be carried out at any single Medical Center, is required. Third, the proposed study is straightforward in design and data analysis, feasible to conduct within the planned time frame at a relatively low cost, and should yield "definitive" results. The variance of the measures and the magnitude of the expected change are known, so that the appropriate sample size can be planned. Finally, since there are no alternative treatments for TD, and since vitamin E is both safe and inexpensive, a definitively positive outcome from this study would have widespread effects on prevailing clinical practice. This presentation will focus on the public health and study design aspects of planning this Cooperative Study. (2) Lohr et al. Alphatocopherol in tardive dyskinesia. Lancet 1987; ! :913-934. (3) Adler et aL Vitamin E treatment of tardive dyskinesia. Am J Psychiatry 1993; 150:1405-1407.