A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia. Treatment of tardive dyskinesia with vitamin E. Vitamin E in the treatment of tardive dyskinesia. Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group. Treatment of long-term tardive dyskinesia with vitamin E. Long-term treatment effects of vitamin E for tardive dyskinesia. Effectiveness of vitamin E for treatment of long-term tardive dyskinesia. Vitamin E in the treatment of tardive dyskinesia: a preliminary study over 7 months at different doses. Vitamin E in the treatment of tardive dyskinesia.
This study was designed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia (TD).
                Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were randomly assigned to receive 800 IU b.i.d. of vitamin E and 18 were assigned to placebo for 2 months. Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder. Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale (mAIMS), Simpson-Angus Scale for extrapyramidal side effects, and Brief Psychiatric Rating Scale. Additionally, a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia.
                There was a significant reduction of dyskinesia in the vitamin E group, but not the placebo group, on both the mAIMS and the instrumental assessments. The overall reduction in mAIMS in the active group was 24%, with 5 (29%) of 17 patients demonstrating greater than 33% reduction in score. There was a greater reduction in mean mAIMS score (35%) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction (11%) in patients with TD for greater than 5 years. No change was observed in parkinsonism. In the patients with schizophrenia, there was a reduction in positive symptoms after vitamin E.
                Vitamin E appears to be effective in reducing the severity of TD, especially in patients who have had TD for 5 years or less. Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group.
                Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis.
                Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment.
                Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications. Eight subjects with persistent tardive dyskinesia were treated with vitamin E and placebo in a randomized, double-blind crossover study. Their mean score on the Abnormal Involuntary Movement Scale (AIMS) was significantly lower after treatment with vitamin E than after placebo administration. Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E.
                The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo.
                Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales.
                This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia. nan Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment.
                To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.
                Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score.
                The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo. Eleven patients with tardive dyskinesia were treated in a double-blind study of vitamin E or placebo for 12 weeks. Abnormal Involuntary Movement Scale (AIMS) ratings were performed before and after treatment. Patients receiving vitamin E showed a significant reduction in their AIMS scale score, but patients receiving placebo showed no significant change. Vitamin E had a helpful effect even for patients whose tardive dyskinesia was mild and long-term. Vitamin E has been suggested to be a promising new treatment for tardive dyskinesia. However, little is known about the optimum dose. Twenty patients with tardive dyskinesia whose medication had been unchanged for at least 1 month were selected and randomly divided into a treatment group with 11 patients and a control group with nine patients. The treatment group was started on 600 mg of vitamin E per day, and this dose was increased over the 7 months of the trial to 1600 mg per day. The medication for the control group was unchanged. Severity of tardive dyskinesia was rated on the Abnormal Involuntary Movement Scale. Patients in the treatment group initially showed a significant response to the lower dose of 600 mg per day. However, this improvement was not maintained and differences between the two groups reached significant levels only after the dose of vitamin E was increased to 1600 mg per day. At this dose, there was a significant and sustained reduction in the severity of tardive dyskinesia. The results suggest that vitamin E is of value in the treatment of tardive dyskinesia and that the optimum dose for treating tardive dyskinesia is 1600 mg per day. In addition, there may be a dose related therapeutic effect of Vitamin E in tardive dyskinesia. In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD) was studied in 32 patients. After a two week wash-out phase a baseline (0 week) TD rating was assessed on the tardive dyskinesia rating scale (TDRS). Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg) and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week. All patients were rated on the TDRS at the end of each week. The baseline TDRS score in the vitamin E group was significantly higher than the placebo group. This was hence adjusted and the results were then subjected to analysis of co- variance. The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03).
Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.