Oxidative stress and tardive dyskinesia: role of natural antioxidants



Schizophrenia is a devastating psychiatric disorder that affects 1% of population worldwide. Neuroleptics are the major class of drugs used in the treatment of schizophrenia. Neuroleptics are associated with wide variety of extrapyramidal side effects such as akathesia, dystonia, neuroleptic malignant syndrome, Parkinsonism and tardive dyskinesia. tardive dyskinesia is a complex hyperkinetic syndrome consisting of choreiform, athetoid or rhythmic abnormal involuntary movements. The face, mouth and tongue are most frequently involved (orofacial type), but a variety of less frequent motor abnormalities of the upper and lower limbs and of the trunk may also occur. Estimates of the prevalence rate of TD in patients receiving neuroleptics range from 0.5%-70% with an average prevalence rate of 24%. Despite much research, the pathogenesis of TD remains elusive. So far various neurochemical hypothesis have been proposed for the development of TD. Those include dopaminergic hypersensitivity, disturbed balance between dopamine and cholinergic systems, dysfunctions of striatonigral GABAergic neurons and excitotoxicity. Similarly, different suppressive agents have been tried with limited success. Oxidative stress and products of lipid peroxidation are implicated in the pathophysiology of various neurological disorders including TD. Administration of single or chronic dose of haloperidol to animal led to decrease endogenous antioxidant, reduced glutathione levels in the striatum indicating generation of oxidative stress by the drug. Chronic haloperidol treatment also decreased antioxidant defense enzymes superoxide dismutase (SOD) and catalase levels. Natural antioxidant like vitamin E, melatonin, quercetin and Withania somnifera have shown to be beneficial in ameliorating tardive dyskinesia symptoms in animal models of TD, further supporting the pivotal role of oxidative stress in the pathophysiology of TD. A role of natural antioxidants has been implicated in the management of neurodegenerative disorders including tardive dyskinesia.