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Oxidative Mechanisms and Tardive Dyskinesia

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Abstract

Tardive dyskinesia has been and continues to be a significant problem associated with long-term antipsychotic use, but its pathophysiology remains unclear. In the last 10 years, preclinical studies of the administration of antipsychotics to animals, as well as clinical studies of oxidative processes in patients given anti-psychotic medications, with and without tardive dyskinesia, have continued to support the possibility that neurotoxic free radical production may be an important consequence of antipsychotic treatment, and that such production may relate to the development of dyskinetic phenomena.

In line with this hypothesis, evidence has accumulated for the efficacy of antioxidants, primarily vitamin E (α-tocopherol), in the treatment and prevention of tardive dyskinesia. Early studies suggested a modest effect of vitamin E treatment on existing tardive dyskinesia, but later studies did not demonstrate a significant effect. Because evidence has continued to accumulate for increased oxidative damage from antipsychotic medications, but less so for the effectiveness of vitamin E, especially in cases of long-standing tardive dyskinesia, alternative antioxidant approaches to the condition may be warranted. These approaches may include the use of antioxidants as a preventive measure for tardive dyskinesia or the use of other antioxidants or neuroprotective drugs, such as melatonin, for established tardive dyskinesia.

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Notes

  1. The pathophysiological or pathoanatomical reason why tardive dyskinesia in most individuals primarily involves the lower facial musculature as well as the distal extremities is currently unknown. It is therefore difficult to discuss how free radical—induced toxicity may relate to the specific anatomical distribution of the syndrome. Although one is tempted to speculate that certain brain regions may be more vulnerable than others to the tardive dyskinesia—causing effects of antipsychotics, it is not known what that vulnerability might be. The anatomical regions affected by tardive dyskinesia seem to be dedicated to complex movements, such as those subserving communication functions as with speech and gesture,[8] but again this does not necessarily imply a specific pathophysiological mechanism for tardive dyskinesia. Although it is possible that brain regions involved in the control of complex motor functions may be at greater risk of free radical—induced damage than other regions, there is to the authors’ knowledge no direct evidence for this conjecture.

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Acknowledgements

This work was supported by National Institute of Mental Health Grant R01 57140 and by the Veterans Integrated Service Network (VISN)-22 Mental Illness Research Education and Clinical Center (MIRECC). The authors have provided no information on conflicts of interest directly relevant to the content of this review.

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  1. Department of Psychiatry, University of California San Diego, San Diego, California, USA

    James B. Lohr, Ronald Kuczenski & Alexander B. Niculescu

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  1. James B. Lohr
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Lohr, J.B., Kuczenski, R. & Niculescu, A.B. Oxidative Mechanisms and Tardive Dyskinesia. Mol Diag Ther 17, 47–62 (2003). https://doi.org/10.2165/00023210-200317010-00004

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