Diazepam-induced changes in tardive dyskinesia: Suggestions for a new conceptual model

M. M. Singh, Memphis VA Medical Center
R. E. Becker, Memphis VA Medical Center
R. K. Pitman, Memphis VA Medical Center
H. A. Nasrallah
H. Lal
R. L. Dufresne, University of Rhode Island
S. S. Weber
M. McCalley-Whitters


Using an ABA' research design, the effects of a benzodiazepine γ-aminobutyric acid (GABA)-ergic agent, diazepam, on various aspects of tardive dyskinesia (TD) were investigated in 21 patients. Videotaped recordings of the examinations were rated blind on the Abnormal Involuntary Movement Scale. In nonsedating amounts, diazepam had a significant anti-TD effect, especially in terms of limb dyskinesia. A significant portion of the therapeutic effect persisted after the medication was withdrawn. The results suggest that diazepan has a specific anti-TD action and that in some cases it may be able to produce a somewhat lasting correction of the deranged neurobiological mechanisms in TD. Since the main sites of action of benzodiazepines and the highest concentrations of benzodiazepine-linked GABA receptors are in the limbic and cortical structures that provide principal sources of inputs to the basal ganglia, it is suggested that the supra-striato-pallidal mechanisms of voluntary movement control should be considered in understanding the pathogenesis and treatment of TD.