Tardive Dyskinesia - Etiology

Psychiatric conditions are often treated with drugs called antipsychotic agents, which can be typical or atypical. The typical agents include DRAs that have been shown be associated with TD, including phenothiazines, butyrophenones, dibenzodiazepines, diphenylbutylpiperidines, indolones, and thioxanthenes. Reports on the incidence of TD with the use of newer atypical antipsychotic agents such as clozapine (Clozaril®), olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have varied greatly. Risperidone (Risperdal®) appears to bring out the symptoms of TD more frequently, as compared to the other newer atypical antipsychotic agents.

Drugs other than those used to treat psychiatric illnesses can also block the dopamine receptors, and their use has also been found to be linked to TD. These include anticholinergic drugs and selective serotonin reuptake inhibitors (SSRIs), which are used to treat depression. Whether other antidepressant medication such as monoamine oxidase inhibitors and tricyclics cause TD is not clear. An increased risk of TD may also be associated with the use of certain antihistamines, decongestants, stimulants, and certain drugs used to treat gastrointestinal disorders, seizure disorders, anxiety, and malaria. Evidence that these drugs may be associated with TD is relatively weak. Several populations have been suggested to have an increased risk for developing TD, but further epidemiologic studies are needed to confirm these observations.

Populations at High Risk for Developing TD	Potential Reasons
Elderly women	Decreased estrogen levels and increased phenylalanine levels
Patients who have used dopamine-receptor antagonists (DRAs) for more than 3 months Diabetics, independent of their use of DRAs, although the risk increases with the use of DRAs	Increased exposure to DRAs
Patients with drug-induced parkinsonism	Not related to the use of anticholinergic drugs
Persons with phenylketonuria	Increased phenylalanine levels

	Epidemiology