We are replicating the results of a preliminary outpatient study in which alpha-tocopherol was found to significantly improve measures of tardive dyskinesia, a disorder seen in patients who have had long-term neuroleptic treatment. The current study is a double-blind, placebo-controlled inpatient study using higher doses than the first study and for longer periods. The 4 patients enrolled so far show no adverse reactions. We will examine measures of involuntary movements, neuropsychological functioning, psychopathology, and awareness of presence of abnormal movements before and after treatment. We are studying 4 hypotheses. First, alpha-tocopherol significantly reduces tardive dyskinesia's severity (as measured by the AIMS rating scale), and this change is not due to fluctuations in medication levels. Second, the disorder is associated with abnormalities on MRI scans, including a higher incidence of enlarged ventricles and cortical sulcal prominence compared to age- and gender-matched psychiatric controls. Third, patients with the disorder have lower average IQs than matched controls and do significantly worse on neuropsychological tests of striatal functioning. Finally, alpha-tocopherol improves measures of negative symptoms (as measured on the NSRS) and awareness of movement disorder (as measured by a self-awareness scale).
