What medications can cause tardive dyskinesia?

Medications That Can Cause Tardive Dyskinesia

Tardive dyskinesia (TD) is primarily caused by dopamine receptor-blocking agents (DRBAs), including both first-generation and second-generation antipsychotics, as well as certain gastrointestinal medications like metoclopramide. 1

Primary Causative Medications

Antipsychotic Medications

1. First-Generation (Typical) Antipsychotics

   • Higher risk of causing TD compared to atypical antipsychotics 2
   • Examples include:
     • Haloperidol
     • Chlorpromazine
     • Fluphenazine
     • Thioridazine
     • Perphenazine

2. Second-Generation (Atypical) Antipsychotics

   • Lower risk than typical antipsychotics but still cause TD 3, 4
   • Examples include:
     • Risperidone 5
     • Olanzapine
     • Quetiapine
     • Aripiprazole
     • Ziprasidone

3. Gastrointestinal Medications

   • Metoclopramide - carries FDA black box warning for TD 6
   • Other prokinetic agents with dopamine-blocking properties

Risk Factors and Considerations

Medication-Specific Factors

• Duration of treatment - longer exposure increases risk 2, 6
• Cumulative dose - higher total exposure increases risk 6, 5
• Potency of dopamine receptor blockade - higher potency increases risk 7

Patient-Specific Risk Factors

• Age - older patients have significantly higher risk 1
• Ethnicity - non-Caucasian ethnicity may increase risk 4
• Pre-existing movement disorders
• Gender - some evidence suggests females may be at higher risk
• Diabetes mellitus
• Previous history of EPS 8

Medications with Lower TD Risk

Some medications have relatively lower risk of causing TD:

• Clozapine - lowest risk among antipsychotics 7, 4
• Quetiapine - lower risk compared to other antipsychotics 7
• Pimavanserin - recommended for Parkinson's disease psychosis due to minimal TD risk 8

Monitoring and Prevention

• Regular assessment for abnormal movements using the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months 2, 8
• Baseline assessment before starting any DRBA
• Use lowest effective dose for shortest duration possible 6
• Consider alternative treatments when possible
• Treatment beyond 12 weeks with metoclopramide should be avoided except in rare cases 6

Clinical Presentation

TD typically presents as:

• Involuntary choreiform or athetoid movements
• Orofacial region commonly affected (lip smacking, tongue protrusion)
• Can affect any body part including limbs and trunk
• May persist even after medication discontinuation 2, 6
• Often co-occurs with other drug-induced movement disorders 8

Management Considerations

When TD is detected:

• Consider discontinuation of the causative agent if clinically feasible 2, 7
• If antipsychotic treatment must continue, consider switching to an agent with lower TD risk (clozapine or quetiapine) 7
• VMAT-2 inhibitors (deutetrabenazine, valbenazine) have shown efficacy for TD treatment 7, 9
• Other potential treatments include amantadine, levetiracetam, clonazepam, and propranolol 9

TD represents a significant iatrogenic movement disorder with potential for irreversibility, making prevention through careful medication selection and monitoring the most important clinical strategy.