Did you Know? Tardive Dyskinesia & Drug-Induced Movement Disorders

May 16, 2023 | Clinical Insight

What is Tardive Dyskinesia? [1,2]

Tardive Dyskinesia (TD) is an involuntary movement disorder characterized by uncontrollable, abnormal and
repetitive movements of the face, torso and /or other body parts. The physical symptoms of TD often can be persistent and disruptive to an individual’s emotional and social well-being.

TD is caused by prolonged use of treatments that block dopamine receptors in the brain, such as antipsychotics commonly prescribed to treat mental health conditions including schizophrenia, bipolar disorder, and depression, and certain anti-nausea medications. These medications are referred to as dopamine-receptor blocking agents, or DRBAs. In individuals with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement.

Differentiating Drug-Induced Movement Disorders (DIMDs) [2,3]

It is important to differentiate tardive dyskinesia from acute drug-induced movement disorders, as TD differs in pathophysiology and clinical management. For example, anticholinergic medications may improve drug-induced parkinsonism, and worsen tardive dyskinesia. Characterization and presentation of symptoms, including onset from introduction of the DRBA, can help differentiate these movement disorders to inform an accurate diagnosis and management plan.

Movement Disorder
Onset TimingCommon Distinguishing Features
Tardive dyskinesia (TD)Onset is generally later;
months to years
Repetitive movements: commonly grimacing,
sticking out of tongue or smacking of lips.
■ Movements can include limbs/trunk
■ May be rapid jerking movements or slow writhing movements
Acute Drug-Induced Movement DisordersAcute dystoniaHours to daysPulling, twisting, sustained and repetitive movements that are usually focal.
Acute Drug-Induced Movement DisordersAkathisiaDays to monthsInner feeling of restlessness and inability to
remain seated.
May be associated with foot tapping, shuffling, shifting weight, or rocking, resulting from an urge to move.
Acute Drug-Induced Movement DisordersDrug-induced parkinsonism (DIP)Weeks to months■ Tremor
■ Slowing of movement
■ Rigidity
■ Reduced blink rate
■ Reduced arm swing
■ Flexed posture
■ Shuffling or freezing gait

Monitoring for Drug-Induced Movement Disorders [1]

  • TD is a medication-induced movement disorder associated with prolonged use of dopamine receptor blocking agents (DRBAs), including antipsychotics
■ Chlorpromazine (Thorazine)
■ Molindone (Moban)4
■ Fluphenazine (Prolixin)
■ Loxapine (Loxitane)
■ Haloperidol (Haldol)
■ Perphenazine (Trilafon)
■ Thioridazine (Mellaril)
■ Thiothixene (Navane)
■ Trifluoperazine (Stelazine)
■ Aripiprazole (Abilify)
■ Asenapine (Saphris)
■ Brexpiprazole (Rexulti)
■ Cariprazine (Vraylar)
■ Clozapine (Clozaril)
■ lloperidone (Fanapt)
■ Loxapine (Loxitane)
■ Lumateperone (Caplyta)
■ Lurasidone (Latuda)
■ Olanzapine (Zyprexa)
■ Paliperidone (Invega)
■ Pimavanserin (Nuplazid)
■ Quetiapine (Seroquel,
Seroquel XR)
■ Risperidone (Risperdal)
■ Ziprasidone (Geodon)
■ Prochlorperazine
(Compazine, Compro)
■ Promethazine (Phenergan,
Promethegan, Phenadoz)
■ Trimethobenzamide(Tebamide, Tigan)
■ Thiethylperazine (Torecan)
■ Metoclopramide (Reglan)

The American Psychiatric Association (APA) recommends: [4]

  • Screen for TD before starting or changing DRBA treatment
  • Monitor for signs of TD at every clinical encounter
  • Conduct a structured TD assessment every 6 to 12 months, depending on patient’s risk, and if new or worsening movements are detected at any clinical encounter

The Abnormal Involuntary Movement Scale (AIMS) is the standard structured assessment for the initial
screening and the routine monitoring of TD symptoms.

This 10-minute patient assessment uses a 5-point rating scale for recording movement scores for 7 body areas: face, lips, jaw, tongue, upper extremities, lower extremities, and trunk.

Download: Abnormal Involuntary Movement Scale (AIMS) Worksheet

Treatment Approaches of DRBA-Induced Movement Disorders [3,5]

ActionTDAcute DystoniaAcute AkathisiaDIP
Add VMAT-2 inhibitorImproves (approved for treatment of TD)May worsenInsufficient dataMay worsen
Increase DRBA doseMay initially “mask” symptomsMay trigger or worsenMay trigger or worsenMay trigger or worsen
Discontinue DRBA or reduce doseMay initially reveal or worsen symptoms, over time may lead to improvementImprovesImprovesImproves
Add anticholinergicMay worsenMay improveInsufficient dataImproves (approved for treatment of parkinsonism)
Discontinue anticholinergicMay improveMay worsenInsufficient dataMay worsen

*Anticholinergic agents, such as benztropine, are not recommended for use in patients with tardive dyskinesia, and may aggravate and worsen symptoms in these patients.

VMAT-2 inhibitors are the only FDA-approved treatment for TD, per the 2020 APA Guidelines treatment with
a VMAT-2 inhibitor is recommended in patients with moderate to severe TD and may also be considered in
patients with mild TD. These medications offer the ability to treat TD while preserving stable antipsychotic

VMAT-2 inhibitors reversibly bind a transporter that regulates monoamine uptake from the cytoplasm to the
synaptic vesicle for storage and release. Inhibition of VMAT-2 decreases dopamine release and post-synaptic receptor stimulation, thereby decreasing dyskinesia. The attached table provides a brief comparison of FDA approved VMAT-2 inhibitors valbenazine and deutetrabenazine. [5,6]

Comparison of VMAT-2 Inhibitors for Tardive Dyskinesia

Valbenazine [6,7]Deutetrabenazine [6,8]
Brand nameIngrezzaAustedo
Available dose formulationCapsules: 40, 60, 80 mgTablets: 6, 9, and 12 mg
XR (extended-release) 6, 9 and 24 mg
Other indicationsNoneChorea associated with Huntington’s disease
Contraindications relevant to TDNoneHepatic impairment, use of reserpine, MAOIs, tetrabenazine or valbenazine
Warnings and precaution contained in Highlights of Prescribing InformationSomnolence; QT interval prolongationQT interval prolongation; neuroleptic malignant syndrome; akathisia, agitation, restlessness, and parkinsonism (latter not applicable to TD); sedation/somnolence
Dosing frequencyOnce dailyTwice daily (IR) Once daily (XR)
Recommended dosingTake with or without food; start at 40 mg daily, increase to 80 mg daily after 1 weekTake with food; start at 12 mg/day, increase by 6 mg/day at weekly intervals up to 48 mg/day, based on tolerability and response
CYP2D6 poor metabolizersMaximum recommended dose is 40 mg/ dayMaximum recommended dose is 36
Hepatic impairmentModerate-to-severe hepatic impairment: maximum recommended dose is 40 mg/dayContraindicated
Renal impairmentDosage adjustments are not necessary for patients with mild, moderate, or severe renal impairmentPackage insert does not provide any recommendations (cites a lack of studies in this population), but the metabolites are excreted renally
Drug-drug interactionsValbenazine increases digoxin levels;
consider valbenazine dose reduction with strong CYP2D6 inhibitors; with strong CYP3A4 inhibitors the maximum recommended dose is 40 mg daily; use is not recommended with MAOIs or CYP3A4 inducers
Additive sedation may occur with alcohol and other CNS depressants; with strong CYP2D6 inhibitors, the recommended maximum dose is 36 mg/day
QT prolongation recommendationIf the patient is at increased risk for QT prolongation, assess QT interval before increasing the doseIf the patient is at increased risk for QT prolongation, assess QT interval before and after increasing the dose above 24 mg/day


  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders-Text Revision. 5th ed. Arlington, VA: American Psychiatric Association; 2022.
  2. Ward, K. M., & Citrome, L. (2018). Antipsychotic-Related Movement Disorders: Drug-Induced Parkinsonism vs. Tardive Dyskinesia-Key Differences in Pathophysiology and Clinical Management. Neurology and therapy, 7(2), 233–248. https://doi.org/10.1007/s40120-018-0105-0
  3. Hauser, R. A., Meyer, J. M., Factor, et al. (2022). Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice. CNS spectrums, 27(2), 208–217. https://doi.org/10.1017/S109285292000200X
  4. Keepers, G. A., Fochtmann, L. J., Anzia, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. The American journal of psychiatry, 177(9), 868–872. https://doi.org/10.1176/appi.ajp.2020.177901
  5. Bhidayasiri, R., Jitkritsadakul, O., Friedman, J. H., et al. (2018). Updating the recommendations for treatment of tardive syndromes: A systematic review of new evidence and practical treatment algorithm. Journal of the neurological sciences, 389, 67–75. https://doi.org/10.1016/j.jns.2018.02.010
  6. Touma, K. T. B., & Scarff, J. R. (2018). Valbenazine and Deutetrabenazine for Tardive Dyskinesia. Innovations in clinical neuroscience, 15(5-6), 13–16.
  7. Ingrezza (valbenazine) capsules package insert. San Diego, CA: Neurocrine Biosciences, Inc.; 2021 Apr
  8. Austedo and Austedo XR (deutetrabenazine) tablets package insert. Parsippany, NJ: Teva Neuroscience, Inc.; 2023 Feb

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Paul Nolan

As a Consultant Pharmacist, Paul focuses on improving care coordination using best practices to reduce rehospitalizations.

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