Oxidative stress and the antipsychotic-induced vacuous chewing movement model of tardive dyskinesia: evidence for antioxidant-based prevention strategies.

Abstract

Despite decades of research, tardive dyskinesia (TD) remains a poorly understood iatrogenic movement disorder with few effective treatments and no known cure. Accordingly, the development of an innocuous strategy to prevent or mitigate antipsychotic (AP)-associated TD would represent an important clinical advance. Supporting evidence for antioxidant (AX)-based treatment regimens can be found in the preclinical literature, where AP-induced vacuous chewing movements (VCMs) in rats are attenuated by the concurrent administration of direct and indirect AXs. Our aim was to review the preclinical literature examining the role of AX-promoting treatments in the prevention of AP-induced VCMs in rats. A literature search using Google Scholar and PubMed was performed. Relevant results were qualitatively reviewed. Studies featuring a variety of naturally occurring and synthetic AX treatments were identified and included in the review. The majority of studies used haloperidol (HAL), a typical AP, to induce VCMs. Studies revealed reduced VCMs in co-treated rats, with favorable changes seen in markers of oxidative stress (OS) and AX status, but were limited by their short durations. Some preclinical evidence suggests that the inclusion of a naturally occurring and benign AX compound as an adjunct to AP treatment may help guard patients against TD, but additional long-duration studies are needed. This AX-based strategy is further substantiated by accumulating evidence of preexisting OS abnormalities in schizophrenia (SZ).