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Vitamin E improves tardive dyskinesia

Clinical bottom line: There is some evidence that vitamin E reduces the symptoms of tardive dyskinesia with no increase in reported adverse effects. However, the trials were small and of short duration meaning that the results of the meta-analysis are not robust.

Tardive dyskinesia is a late side-effect of neuroleptic treatment. It is an involuntary movement disorder, mainly of the tongue, lips, jaw, facial musculature and trunk. It affects up to 50% of chronic, psychotic patients. There is no known treatment.

Systematic review:

Soares KVS, McGrath JJ. Vitamin E for neuroleptic-induced tardive dyskinesia (Cochrane Review). In: The Cochrane Library, Issue 3, 2000. Oxford: Update Software.

Date review completed: 1998 (updated February 1999)

Number of trials included: Eight

Number of patients: (110 vitamin E; 96 placebo)

Control groups: placebo or no intervention.

Main outcomes: Peto Odds Ratio; NNT for at least 50% improvement; NNT for any improvement; 95% confidence intervals.

Inclusion criteria were: randomised controlled trial; neuroleptic-induced tardive dyskinesia (TD) in patients with schizophrenia or other chronic mental illness; treatment groups which included vitamin E and either placebo or no intervention; treatment with neuroleptics for more than three months. An extensive search of Biological Abstracts, The Cochrane Schizophrenia Group's Register, EMBASE, LILACS, MEDLINE, PsychLit, SCISEARCH, handsearching of reference lists was conducted. Authors of included studies were contacted. Data from placebo controlled trials were combined in a meta-analysis.


The included trials were randomised, double blind, assessed mainly schizophrenic men in their 50's, assessed vitamin E 1200-1600 IU/day, and had between 10-55 participants. Only one study was of more than 12 weeks duration. With vitamin E treatment, the overall NNT for at least 50% improvement in the symptoms of TD was 5 (2.4 to 31) based on 78 patients. The NNT for any improvement was 4 (2.5 to 12) based on 143 patients. The symptoms of TD patients who did not receive vitamin E treatment worsened.

Adverse effects

No significant difference between vitamin E and placebo was shown for adverse effects.



The reviewers' correctly pointed out the flaws in these trials, mainly that they were small and of short duration or used a cross-over design. Since vitamin E is fat-soluble it may remain in the body for some time. Cross-over trials are not appropriate when a carry-over effect is likely, unless adequate washout periods are used. Another systematic review [1] also shows a modest improvement in the symptoms of TD with use of vitamin E (400-1600 IU/day). The review by Soares & McGrath has been more recently updated, discusses issues of quality/validity in more detail and so was considered in preference. The toxicity of vitamin E is low, but high levels may affect the absorption of vitamins A and K and over long-term use may result in nausea, diarrhoea and blurred vision [2].

Further reading

1. Barak Y, Swarta M, Smair E, Stein D, Weizman A. Vitamin E (µ-tocopherol) in the treatment of tardive dyskinesia: A statistical meta-analysis. Ann Clin Psych 1998; 10(3): 101-105.

2. Kaegi E and the task Force on Alternative therapies of the Canadian Breast Cancer Research Initiative. Unconventional therapies for cancer: 5. Vitains A, C and E. CMAJ 1998; 158(11): 1483-1488.

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AT051 - 7206 Vitamin E improves tardive dyskinesia: Aug-2000