Tardive dyskinesia (TD), a potentially irreversible
antipsychotic (AP)-related
movement disorder, is a risk with all currently available
antipsychotics. AP-induced vacuous chewing movements (VCMs) in rats, a preclinical model of TD, can be attenuated by
antioxidant-based treatments although there is a shortage of well-designed studies.
Lipoic acid (LA) represents a candidate
antioxidant for the treatment of oxidative stress-related
nervous system disorders; accordingly, its effects on AP-induced VCMs and striatal oxidative stress were examined. Rats treated with
haloperidol decanoate (HAL; 21mg/kg every 3weeks, IM) for 12weeks were concurrently treated with LA (10 or 20mg/kg, PO). VCMs were assessed weekly by a blinded rater, and locomotor activity was evaluated as were striatal lipid peroxidation markers and serum HAL levels. VCMs were decreased by the lower dose (nonsignificant), whereas a significant increase was recorded with the higher dose of LA. HAL decreased locomotor activity and this was unaffected by LA. Striatal
malondialdehyde (MDA) levels in HAL-treated rats were reduced by both LA doses, while
4-hydroxynonenal (4-HNE) levels were predictive of final VCM scores (averaged across weeks 10-12). Study limitations include differences between
antipsychotics in terms of oxidative stress, LA dosing, choice of
biomarkers for lipid peroxidation, and generalizability to TD in humans. Collectively, current preclinical evidence does not support a "protective" role for
antioxidants in preventing TD or its progression, although clinical evidence offers limited evidence supporting such an approach.