## Tardive Dyskinesia Risk Among Antipsychotics **Key Point:** Tardive dyskinesia (TD) is a late-onset involuntary movement disorder caused by prolonged dopamine D2 receptor blockade. Risk is directly proportional to potency of D2 blockade and duration of exposure. ### Risk Stratification by Drug Class | Antipsychotic Class | TD Risk | Mechanism | | --- | --- | --- | | **First-generation (typical)** | Very High | High-potency D2 blockade; haloperidol most notorious | | **Second-generation (atypical)** | Low–Moderate | Weaker D2 affinity; faster dissociation from D2 | | **Clozapine** | Lowest | Unique: may reverse existing TD | **High-Yield:** Haloperidol is a high-potency typical antipsychotic with strong, sustained D2 receptor antagonism. Incidence of TD with haloperidol is 5–10% per year in older adults, making it the highest-risk agent among the options. **Clinical Pearl:** Clozapine is paradoxically protective against TD and may even improve pre-existing tardive dyskinesia, likely due to its rapid D2 dissociation and serotonergic activity. ### Why Other Options Are Lower Risk - **Quetiapine:** Atypical agent with weaker D2 affinity and rapid dissociation; TD risk ~0.5–1% per year. - **Aripiprazole:** Partial D2 agonist; does not cause sustained blockade; TD risk negligible. - **Clozapine:** Lowest TD risk; may reverse existing dyskinesia.
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