What Drugs Cause Tardive Dyskinesia?

Tardive dyskinesia most commonly occurs in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who have undergone long-term treatment with antipsychotic medications.

Tardive dyskinesia is involuntary, repetitive body movements of the face, lips, tongue, trunk, and extremities that occur in patients treated with dopaminergic antagonist medications (antipsychotics). It most commonly occurs in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who have undergone long-term treatment with antipsychotic medications but it can occur in other patients as well.

Tardive dyskinesias are a symptom in themselves, characterized by extrapyramidal movements. Extrapyramidal movements refer to automatic movements and fixed, postural movements that are not visible. Extrapyramidal symptoms involve movement disorders (dyskinesias) such as:

• Restlessness/inability to sit still (akathisia) 
• Involuntary and unpredictable body movements, ranging from fidgeting to problems with speech, swallowing, and posture (chorea)
• Involuntary muscle contractions (dystonia)
• Involuntary muscle twitching or jerking (myoclonus)
• Repetitive movements, gestures, word repetition (stereotypy)
• Sudden repeated, twitches, movements, or sounds (tics)
• Shaking (tremors)

The main cause of tardive dyskinesia is long-term use of dopaminergic antagonist medications (antipsychotic medications). 

Dopamine antagonists that can cause tardive dyskinesia include:

• Antipsychotic drugs (neuroleptics) 
  • Butyrophenones: droperidol (Inapsine), haloperidol (Haldol), dibenzodiazepines [such as clozapine (Clozaril)], loxapine (Loxitane)
  • Diphenylbutylpiperidines: pimozide (Orap)
  • Indolones: molindone (Moban)
  • Phenothiazines: chlorpromazine (Thorazine), fluphenazine (Prolixin), mesoridazine (Serentil), perphenazine, thioridazine, trifluoperazine (Stelazine)
  • Thioxanthenes: thiothixene (Navane)

• Newer atypical antipsychotic agents (only sometimes linked to tardive dyskinesias)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Risperidone (Risperdal)
  • Paliperidone (Invega)
  • Amisulpride (Solian, Socian, Deniban)
• Other drugs that can cause tardive dyskinesia include:
  • Metoclopramide (Reglan), especially in the elderly
  • Antihistamines 
  • Fluoxetine (Prozac, Sarafem)
  • Amoxapine (Asendin)

Tardive dyskinesia is typically diagnosed by a history and physical exam, noting whether the patient takes dopaminergic antagonist medications.

Diagnosis of conditions that can resemble tardive dyskinesia such as seizure disorders, advanced syphilis, thyroid disease, and Wilson disease is also important. 

Tests that may be indicated to diagnose other conditions may include:

• Lab tests such as serum ceruloplasmin, urine copper collection, liver function tests, liver transaminases, copper transporter gene
• Computed tomography (CT) scans
• Magnetic resonance imaging (MRI)
• Positron emission tomography (PET) scans 
• Single-photon emission computed tomography (SPECT) scans
• Electroencephalography (EEG) 
• Complete ophthalmologic evaluation, including slit-lamp examination

Other tests may be indicated, such as:

• Thyroid function tests to exclude thyroid dysfunction
• Blood tests: chemistry panel, thyroid function tests, and syphilis serology 
• Connective tissue disease screening tests 
• Red blood cell (RBC) counts 
• Serum calcium level

Treatment for tardive dyskinesia may involve reevaluating and adjusting medications (do not stop taking any medication without first consulting your doctor). 

Medications may be used to help counteract the symptoms of tardive dyskinesia, such as:

• Clonazepam (Klonopin)
• Ginkgo biloba (tell your doctor before taking any herbal supplements as these may have unwanted side effects or interactions with medications you use)
• Valbenazine (Ingrezza)
• Deutetrabenazine (Austedo) 

Other drugs for which there is some anecdotal support in terms of reduction of tardive dyskinesia symptoms include:

• Vitamin E
• Levodopa
• Benzodiazepines
• Botulinum toxin (Botox)
• Reserpine (Resa Oral, Reserpoid Oral, Sandril Oral, and others)
• Tetrabenazine (Xenazine)
• Propranolol (Inderal)
• Dopamine-depleting 
• Ondansetron (Zofran)

Psychotherapy may also help patients deal with the emotional distress caused by tardive dyskinesia symptoms and their effects.  

Patients with certain disorders such as schizophrenia, developmental disabilities, fetal alcohol syndrome, and other neuropsychiatric disorders may be more vulnerable to tardive dyskinesia when prescribed dopamine-receptor blocking drugs. In these cases, tardive dyskinesia may be prevented by avoiding the use of these drugs.