Tardive Dyskinesia in the Era of Typical and Atypical Antipsychotics. Part 1: Pathophysiology and Mechanisms of Induction

Abstract

Although the ultimate model for TD is not yet understood, it is plausible that several of these vulnerabilities and mechanisms act together to produce TD. The lower incidence of TD with atypical antipsychotics has helped to elucidate the,mechanisms of TD.

Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder

“…Subtracting the estimated frequency of spontaneous dyskinesia (5 %) they concluded that the true prevalence was probably around 15 % [28]. Another review of 76 studies conducted through 1989 indicated that the overall Table 1 Proposed pathophysiological mechanisms of tardive dyskinesia [7,116,117] Proposed mechanism Support D2 receptor up-regulation with subsequent hypersensitivity Rodent models demonstrate universal, reversible D2 receptor up-regulation after exposure to dopamine receptor blockers (DRBs); findings not supported by human studies using imaging and immunohistochemistry GABA insufficiency GAD and GABA levels are diminished in the substantia nigra and external pallidum in animal models and in the spinal fluid of humans with TD; levels correlate with vacuous chewing movements (VCMs); findings not consistently replicated; human studies using GABA agonists have been disappointing Increased opioids (encephalin and dynorphin)…”

Atypical Antipsychotics: CATIE Study, Drug-Induced Movement Disorder and Resulting Iatrogenic Psychiatric-Like Symptoms, Supersensitivity Rebound Psychosis and Withdrawal Discontinuation Syndromes

“…For example, it is hard to believe that in a recent review of psychomotor slowing in schizophrenia, the authors, when evaluating its effect on measurement and treatment research to improve cognition in schizophrenia (MATRICS), nearly completely ignored the influence of akinesia and DIMD on neuropsychological tests in schizophrenia and the importance of accurate DIMD measurements [7]. As we pursue this ongoing discussion, we recommend the discontinuation of all classical antipsychotics due to their neurotoxic association with a high prevalence of DIMD and increases in basal ganglia volumes [8], and now address how to prescribe atypical antipsychotics most effectively, by taking into account DIMD-associated psychiatric symptoms and iatrogenic discontinuation syndromes.…”

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia

“…2 In contrast to classic orobuccolingual tardive dyskinesia, TD is largely irreversible with 90% of patients failing to achieve remission at a mean follow-up of 6.6 years. 13 The limitations of medical treatment reflect incomplete understanding of the complex pathophysiology of TD. Multiple theories have been proposed of which the most prominent describe postsynaptic dopamine receptor hypersensitivity, degeneration of striatal cholinergic neurons, and gamma-amino-butyric acid-containing neurons.…”

“…Multiple theories have been proposed of which the most prominent describe postsynaptic dopamine receptor hypersensitivity, degeneration of striatal cholinergic neurons, and gamma-amino-butyric acid-containing neurons. 13 In contrast, the success of pallidal DBS in the treatment of primary dystonias led to its adoption for secondary dystonias such as TD. [5][6][7]14,15 In this series we demonstrate a significant beneficial effect for medically refractory TD where rapid remarkable improvements in motor symptoms were observed within days without exacerbation of psychiatric symptoms.…”