Biological Basis of Neuroleptic-Induced Neurological Syndromes

BIOLOGICAL BASIS OF NEUROLEPTIC-INDUCED NEUROLOGICAL SYNDROMES 

TD is a more delayed reaction, probably based in part on the development of reactive supersensitivity or hyperactivity in these same striatal dopamine receptors following continuous blockade (see APA, 1980b  

Fann et al., 1980 Klawans, 1973 and chapter 5 in this volume). This supersensitivity of the dopamine receptors becomes most obvious when the drug is reduced or eliminated, terminating the blockade. The over-active, unblocked receptors produce the TD symptoms. Undoubtedly, a great deal more must be learned about the neuropathology of both these drug-induced diseases, which probably involve multiple neurotransmitter system abnormalities. However, if health care providers were to stop prescribing these drugs to patients, the problem would virtually disappear. 

More recent studies have indicated that TD may be the result of complex interactions between dopamine and the cholinergic system, which becomes more active when the suppressive or balancing effect of the dopaminergic system is blocked by the neuroleptics. In addition, the neuroleptics are directly toxic to neurons by means of disrupting a number of separate biochemical pathways (chapter 5). 

In an editorial titled Gaining Pediatric Patients and Use of Atypical Antipsychotics, published in the American Journal of Psychiatry in December 2006, Tobin stated  

---