Nearly 1% of the world population suffers from
schizophrenia, and
neuroleptics are the major class of drugs used to treat this disorder.
Neuroleptics are associated with wide variety of extrapyramidal side effects, such as akathesia,
dystonia,
neuroleptic malignant syndrome, Parkinson-ism and
tardive dyskinesia. Despite the awareness that
neuroleptics could cause extrapyramidal side effects, these drugs remain the most effective means of treating
schizophrenia and
Tourette's syndrome, as well as for the management of behavioral disorders in developmentally disabled individuals.
Tardive dyskinesia is a complex
hyperkinetic syndrome consisting of choriform, athetoid or rhythmically abnormal
involuntary movements. Estimates of the prevalence rate of
tardive dyskinesia in patients receiving
neuroleptics range from 0.5-70%, with an average prevalence rate of 24%. Despite much research, the pathogenesis of
tardive dyskinesia remains elusive. So far, various neurochemical hypotheses have been proposed for the development of
tardive dyskinesia. These 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. Recently, the role of oxidative stress and structural abnormality in the pathophysiology of
tardive dyskinesia has gained much impetus. Induction of
free radicals by
neuroleptic drugs leading to the oxidative stress and resultant structural abnormality could be the key factor in the pathogenesis of
tardive dyskinesia. This hypothesis has been supported by numerous reports that chronic
neuroleptic treatment increases
free radical production and causes structural damage. More recently, the genetic vulnerability for the predisposition for the development of
tardive dyskinesia, i.e., pharmacogenetic aspect of
tardive dyskinesia, is also gaining impetus as a research area, and is discussed in detail in this article.