Fast Five Quiz: Tardive Dyskinesia Risk Factors

Christoph U. Correll, MD; James Robert Brasic, MD, MPH


April 11, 2022

Antipsychotic medications, particularly conventional, typical, or first-generation antipsychotics (eg, chlorpromazine, mesoridazine, haloperidol), tend to be associated with prototypical orofacial TD. Atypical antipsychotics, such as risperidone, olanzapine, aripiprazole, and clozapine, appear to have a lower risk for TD. In a meta-analysis of randomized controlled trials, TD risk ratio (RR) was lower with second-generation vs first-generation antipsychotics (RR = 0.47; 95% CI, 0.39-0.57; P < .0001). Similarly, the TD annualized rate ratio (RaR) was also lower with second-generation vs first-generation antipsychotics (RaR = 0.35; 95% CI, 0.28-0.45; P < .0001; number needed to treat = 20).

A prospective cohort study analyzed the incidence of TD with atypical vs conventional antipsychotic medications. Compared with subjects treated with conventional antipsychotics alone, the adjusted TD incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). Therefore, while the risk for TD appears to be higher with conventional antipsychotics, clinicians should monitor for TD in patients treated with atypical antipsychotics as well.

Although TD has been observed after exposure to various substances, including central nervous system agents (such as levodopa), amphetamines, and prokinetic agents (such as metoclopramide), the prototypical TD is the orofacial (ie, buccolingual, masticatory) hyperkinesia induced by antipsychotic dopamine D2-receptor blockers, especially of the first generation.

Upon presentation of TD, clinicians should inquire about medications, including amphetamines, levodopa, and substances that may cause dyskinesias. Specifically ask whether antiemetic medications (especially metoclopramide, prochlorperazine, and related compounds) are being administered.

Learn more about the diagnostic considerations of TD.


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