What medications cause Tardive dyskinesia?

Medications That Cause Tardive Dyskinesia

Typical antipsychotics (first-generation antipsychotics) are the medications most strongly associated with tardive dyskinesia, with up to 50% of elderly patients developing this condition after 2 years of continuous use. 1 These medications carry a significantly higher risk compared to atypical (second-generation) antipsychotics.

High-Risk Medications

First-Generation (Typical) Antipsychotics

• Haloperidol (Haldol)
• Fluphenazine (Prolixin)
• Thiothixene (Navane)
• Trifluoperazine (Stelazine)
• Molindone (Moban)
• Perphenazine (Trilafon)
• Loxapine (Loxitane)

These medications have strong dopamine D2 receptor antagonism, which is the primary mechanism behind tardive dyskinesia development. The risk is particularly high with long-term use.

Other Medications Associated with TD

• Metoclopramide (Reglan) - A prokinetic agent used for gastrointestinal disorders that carries a black box warning for tardive dyskinesia 2
• Prochlorperazine - An antiemetic with antipsychotic properties
• Other dopamine receptor blocking agents

Lower-Risk Medications

Second-Generation (Atypical) Antipsychotics

These medications have a reduced but still present risk of tardive dyskinesia:

• Risperidone (Risperdal) - May cause extrapyramidal symptoms at doses of 2 mg/day or higher 1
• Olanzapine (Zyprexa)
• Quetiapine (Seroquel) - Has a black box warning for tardive dyskinesia, though risk is lower than with typical antipsychotics 3
• Clozapine - Generally considered to have the lowest risk among antipsychotics
• Ziprasidone
• Aripiprazole

The annual incidence of tardive dyskinesia with second-generation antipsychotics is approximately 0.8% in adults, compared to 5.4% with haloperidol 4. However, the risk increases significantly with age, reaching 5.3% in patients 54 years and older 4.

Risk Factors for Developing Tardive Dyskinesia

1. Duration of treatment - Risk increases with longer exposure
2. Total cumulative dose - Higher lifetime doses increase risk
3. Age - Elderly patients are at significantly higher risk
4. Gender - Women, especially elderly women, have higher risk
5. Pre-existing conditions - Patients with diabetes or mood disorders may have increased susceptibility
6. Previous extrapyramidal symptoms - History of acute dystonic reactions may predict TD risk

Clinical Presentation

Tardive dyskinesia typically manifests as:

• Involuntary, repetitive movements of the orofacial region (lip smacking, tongue protrusion)
• Choreiform movements of the extremities
• Athetoid movements of the trunk
• In some cases, respiratory dyskinesia affecting breathing patterns 1

Monitoring and Prevention

1. Baseline assessment - Document any abnormal movements before starting antipsychotics
2. Regular monitoring - Use the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months 1
3. Medication selection - Choose atypical over typical antipsychotics when possible
4. Dose optimization - Use the lowest effective dose
5. Duration limitation - Avoid treatment beyond 12 weeks when possible 2

Management When TD Develops

If tardive dyskinesia is detected:

1. Consider discontinuation of the causative medication if clinically feasible
2. Switch to a lower-risk agent with less D2 affinity (e.g., quetiapine or clozapine) 5
3. Consider VMAT inhibitors (deutetrabenazine, valbenazine) which have shown efficacy in treating TD 5

Remember that TD may persist even after discontinuation of the causative medication, and in some cases may be irreversible 1. Early detection and intervention are critical to minimize long-term disability.