What medications or substances are known to cause tardive dyskinesia?

From the Guidelines

Tardive dyskinesia is primarily caused by long-term use of dopamine receptor blocking agents, with antipsychotic medications being the most common culprits, and metoclopramide, a prokinetic agent, is also known to cause this condition, particularly with use beyond 12 weeks, as noted in the most recent study 1.

Medications Known to Cause Tardive Dyskinesia

• First-generation (typical) antipsychotics like haloperidol, chlorpromazine, fluphenazine, and perphenazine carry the highest risk, as stated in 1 and 1.
• Second-generation (atypical) antipsychotics such as risperidone, olanzapine, quetiapine, and aripiprazole also cause tardive dyskinesia but generally at lower rates, as mentioned in 1.
• Other medications that can trigger this condition include metoclopramide (used for gastrointestinal disorders), prochlorperazine (for nausea and vomiting), and certain mood stabilizers like lithium, as noted in 1 and 1.
• Antiemetics with dopamine-blocking properties such as promethazine can also be responsible, as stated in the example answer.

Risk Factors

• The risk increases with higher doses, longer duration of use (typically months to years), older age, female gender, and presence of mood disorders, as mentioned in the example answer.
• Tardive dyskinesia develops because these medications block dopamine receptors in the basal ganglia, leading to receptor hypersensitivity over time, as explained in 1.

Clinical Implications

• This hypersensitivity causes abnormal involuntary movements, particularly affecting the face, tongue, and extremities, which may persist even after discontinuation of the causative medication, as noted in 1 and 1.
• The most recent study 1 highlights the importance of balancing the benefits of metoclopramide against its potential risks, including the risk of tardive dyskinesia, especially with long-term use.

From the FDA Drug Label

Tardive Dyskinesia (see Boxed Warnings) Treatment with metoclopramide can cause tardive dyskinesia (TD), a potentially irreversible and disfiguring disorder characterized by involuntary movements of the face, tongue, or extremities. A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs, including quetiapine Tardive Dyskinesia As with all antipsychotic agents, haloperidol has been associated with persistent dyskinesias Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may appear in some patients on long-term therapy or may occur after drug therapy has been discontinued.

The medications or substances known to cause tardive dyskinesia are:

• Metoclopramide 2
• Quetiapine 3, an antipsychotic drug
• Haloperidol 4, an antipsychotic agent These medications can cause involuntary movements of the face, tongue, or extremities, and the risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose.

From the Research

Medications Known to Cause Tardive Dyskinesia

• Antipsychotic medication, particularly first-generation antipsychotics 5, 6
• Neuroleptic drugs, which can block dopamine receptors 5, 7
• Anti-emetics, which can also block dopamine receptors 7
• Specific medications mentioned include:
  • Haloperidol, which was used in a case study where a patient developed tardive dyskinesia after short-term, low-dose therapy 8
  • Clozapine and quetiapine, which are second-generation antipsychotics that may be used to reduce tardive dyskinesia symptoms, but can also cause the condition 6, 9

Substances and Risk Factors

• Dopamine-blocking agents, which are commonly used to treat psychiatric conditions 5, 7, 9
• Risk factors for developing tardive dyskinesia include:
  • Age, with older adults being at higher risk 5
  • Female sex 5
  • Affective disorders 5
  • Total drug exposure, with longer treatment durations increasing the risk of developing tardive dyskinesia 5, 6