Tardive Dyskinesia

The pathophysiology of TID is not well understood

Striatal dopamine receptor supersensitivity may be responsible.

Central dopamine blockade is hypothesized to play a role in the pathogenesis'of TD.

Chronic dopamine blockade may result in up‑regulation of dopamine receptor responsiveness.

TD is hypothesized to result from compensatory supersensitivity of dopamine receptors following chronic blockade. Long‑term blockade of dopamine D2 receptors in the basal ganglia by dopamine D2 antagonists (eg, neuroleptics) may produce TD.

When dopamine receptor blockade is reduced (even slightly), an exaggerated response of the postsynaptic dopamine receptor (even to low concentrations of dopamine) may result.

Striatal disinhibition of the thalamocortical pathway from imbalance of D1 and D2 receptors may be involved.

Neurodegeneration secondary to lipid peroxidation or excitotoxic mechanisms may e responsible.

Mounting evidence exists that for some individuals, the dopamine D3, D4, and D5 receptors are involved.