Clinical meaning
Tardive dyskinesia (TD) is a medication-induced hyperkinetic movement disorder characterized by involuntary, repetitive, purposeless movements, most commonly affecting the orofacial muscles (tongue protrusion, lip smacking, chewing movements, grimacing), but also involving the extremities (choreiform movements of fingers, toes) and trunk (rocking, pelvic thrusting). TD results from chronic exposure to dopamine receptor-blocking agents (DRBAs), primarily typical (first-generation) antipsychotics and, less commonly, atypical (second-generation) antipsychotics and antiemetics (metoclopramide, prochlorperazine). The pathophysiology involves dopamine D2 receptor supersensitivity: chronic D2 receptor blockade causes compensatory upregulation and increased sensitivity of postsynaptic D2 receptors in the nigrostriatal pathway (basal ganglia). When the medication is continued, these supersensitive receptors respond excessively to even normal dopamine levels, producing hyperkinetic movements. Additional mechanisms include oxidative stress to basal ganglia neurons, GABA-ergic neuron degeneration, and disruption of the balance between direct and indirect basal ganglia pathways. Risk factors for developing TD include older age (elderly have less dopaminergic reserve), female sex (postmenopausal women at highest risk), longer duration and higher cumulative dose of DRBA exposure, African American descent, pre-existing mood disorders, cognitive impairment, diabetes mellitus, and history of early extrapyramidal...