Reply from Waddington

It is concluded that the clinical pharmacology of TD does not necessarily argue for an absolute over-activity of cerebral dopamine mechanisms (possibly receptors), and there is no direct evidence for even the limited version of the dopamine receptor supersensitivity hypothesis of TD.

Abstract

The tardive dyskinesia refers to a syndrome of abnormal, involuntary, choreoathetoid movements that emerges as a late-onset, adverse effect of long-term treatment with neuroleptic drugs. This syndrome is seen only in a proportion of patients so treated, and when present can affect the orofacial, limb, and trunk regions of the body and the respiratory musculature; classical buccal-lingualmasticatory dyskinesia is perhaps the most widely considered manifestation. Concept of tardive dyskinesia including phenomena such as tardive dystonia, tardive Tourette syndrome, and tardive akdthisia. Clearly, to investigate the syndrome of tardive dyskinesia, one must exclude patients with extrapyramidal disorders, such as Huntington's disease, which are known to involve involuntary, choreoathetoid movements as an inherent feature of the illness independent of any possible exposure to neuroleptics. Evidence supports that long-term treatment with neuroleptics does not cause tardive dyskinesia. Rather, their fundamental action in this regard may be (1) to interact with a neurological process that is (usually) an intrinsic neurodevelopmental or atrophic component of the disorder for which that treatment is prescribed, and (2) to hasten the emergence of an inappropriate and overelaborated form of an innate buccal-lingual-masticatory motor pattern that has an unappreciatedly high likelihood of ultimately occurring spontaneously with increasing cerebral dysfunction.