Did You Know? Recognizing and Managing Tardive Dyskinesia (TD)

What is Tardive Dyskinesia (TD)?

Tardive Dyskinesia (TD) is a drug-induced involuntary movement disorder (DIMD) generally of the tongue, lower face, jaw, and extremities (but sometimes also pharyngeal, diaphragmatic, and trunk muscles) that can persist even after the discontinuation or alteration of neuroleptic medication regimens.

Movements may be stereotypic (repetitive, purposeless), choreoathetotic (irregular, dance-like), or athetotic (slow, writhing).

TD usually presents after at least 3 months of antipsychotic use and can lead to chronic dyskinesias if not detected early and managed appropriately.

Who is at Risk for Developing Tardive Dyskinesia (TD)?

Antipsychotic Use (and other dopamine receptor blocking agents – DRBAs) is the Primary Risk Factor for Developing Tardive Dyskinesia (TD)

• Overall antipsychotic medication use has increased across the general population, including children, adolescents, adults and geriatrics.
  • Antipsychotic medications are FDA approved for bipolar disorder, schizophrenia, and adjunct therapy in major depressive disorder.
  • Some antipsychotic medications and dosage forms are approved for acute management of mania and paranoia.
  • They are often used off-label for mood disorders, agitation and behavioral symptoms of dementia, despite black box warnings in this population.
  • Increased broader antipsychotic usage in the general population has increased the incidence rate of TD, although many patients have yet to be diagnosed and treated.
• Longer duration of therapy on an antipsychotic medication increases the risk of developing TD.
  • 45-60% of antipsychotic regimens are prescribed for long-term use.
• Other dopamine receptor blocking agents (DRBAs), such as metoclopramide, can also precipitate development of TD, especially when used for longer durations, and in older adults that may have altered or delayed metabolism of the medication(s).
• Higher incidence with first generation antipsychotics vs. second generation antipsychotics.

PATIENT RISK FACTORS	TREATMENT RISK FACTORS
Age ≥ 50 years	Cumulative exposure to antipsychotics
Diagnosis of mood disorder	Treatment with anticholinergics
Postmenopausal status	History of acute drug-induced movement disorders
Substance abuse	Antidopaminergic (D2) potency of antipsychotic

*adapted from American Diabetes Association 2024 Standards of Care in Diabetes

MEDICATIONS THAT REQUIRE MONITORING FOR TD

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The American Psychiatric Association (APA) recommends:

1. Screen for TD before starting or changing DRBA treatment.
2. Monitor for signs of TD at every clinical encounter.
3. 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.

CMS regulations also state that adverse effects related to antipsychotic medications, including movement disorders such as tardive dyskinesia, need to be screened for and monitored while residents receive these medications in the Skilled Nursing Facility (SNF).

SELECT CMS REGULATIONS & GUIDANCE

CMS Regulations also state that adverse effects related to DRBA therapies (i.e. antipsychotics), such as movement disorders and tardive dyskinesia, must be screened for and monitored while residents receive these medications in the Skilled Nursing Facility (SNF).

Recognize and Report Symptoms of TD

From CMS – Each resident’s medication regimen must be managed and monitored to promote or maintain the resident’s highest practicable mental, physical, and psychosocial well-being.

Select CMS Regulations & Guidance

F757 – §483.45(D) UNNECESSARY DRUGS AND F758 – §483.45(C)(3) AND (E) PSYCHOTROPIC DRUGS	The use of a medication without adequate monitoring may increase the risk of adverse consequences
MEDICATION MANAGEMENT MONITORING FOR EFFICACY AND ADVERSE CONSEQUENCES	Monitoring and accurate documentation of the resident’s response to any medication(s) is essential to evaluate the ongoing benefits as well as risks of various medications
PSYCHOTROPIC MEDICATIONS AND ANTIPSYCHOTIC MEDICATIONS (F758 ONLY GUIDANCE)	Residents who take these medications must be monitored for any adverse consequences. TD is considered a potential adverse consequence
MONITORING OF PSYCHOTROPIC MEDICATIONS	If psychotropic medication is identified as possibly causing or contributing to an adverse consequence, the facility and prescriber must document it in the medical record. TD is considered a potential adverse consequence.

* Select guidance is provided for education and information purposes. See full CMS State Operations Manual for long-term facilities for complete information.

** adapted from Centers for Medicare & Medicaid Services – State Operations Manual Pub. 100-07. Appendix PP – Guidance to Surveyors for Long Term Care Facilities. Baltimore, MD: US Dept of Health and Human Services; 2017

The AIMS Assessment:

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

Tips for performing an AIMS Assessment:

Differentiating Drug-Induced Movement Disorders

	When did onset of movements occur?	What does it look like	How might it change?
Acute Movement Disorders	Acute: hours to months	Akathisia (ex. restlessness), dystonia (ex. muscle contractions), parkinsonism (ex. tremors)	May resolve after discontinuation of antipsychotics
Tardive Dyskinesia	Delayed: months to years	Stereotypic (ex. repetitive, purposeless), athetoid (ex. slow, writhing), choreiform (repetitive, jerky) movements	Symptoms may be masked or revealed by changes in antipsychotic medication regimen

Impacts of TD on Patients’ Wellness and Self-Esteem

Tardive dyskinesia often causes people to become embarrassed about their abnormal movements. Among a sample of 204 patients with tardive dyskinesia, 76% of them were noted to be embarrassed by or self-conscious about their involuntary movements.

Abnormal movements associated with TD can also decrease physical functioning of a patient. These can present as respiratory, orofacial, and truncal dystonia which can interfere with activities of daily life and add unneeded stress to the patient’s life.

These movements have had reported moderately to extremely negative effects on confidence, self-esteem, self-worth, and overall quality of life.

Pharmacological Management of Tardive Dyskinesia:

In previous years, there was no evidence-based treatment for tardive dyskinesia and patients who developed it had no answer for their symptoms. They could be taken off their antipsychotic medications but since TD symptoms are commonly non-reversible, often symptoms persisted despite removal of the DRBA. Recent studies have found strong evidence for the efficacy and tolerability of VMAT2 inhibitors in the treatment of tardive dyskinesia and the use of them as part of a patient and symptom management plan.

American Psychiatric Association (APA) recommends that patients who have moderate to severe
antipsychotic-induced TD be treated with a VMAT2 inhibitor:

• Treatment with a VMAT2 inhibitor can also be considered in mild TD based on factors like patient preference, other impairments, and psychosocial functioning.
• New generation VMAT2 inhibitors are preferred because there is greater evidence supporting their use and tolerability profile.
• Anticholinergic medications should not be used in TD
  • They do not alleviate symptoms and can even aggravate them in some instances.

Options for treatment based on the Modified Delphi Panel Consensus Recommendations:
(Can be any combination of these)

• Consider treatment with a VMAT2 inhibitor
• Review and consider modifying anticholinergic TD regimen
• Review and consider modifying antipsychotic regimen
• Discuss treatment options with the patients or appropriate caregivers

Comparison of VMAT-2 Inhibitors for Tardive Dyskinesia

Brand name	Valbenazine [6,7] Ingrezza	Deutetrabenazine [6,8] Austedo
Available dose formulation	Ingrezza: 40, 60, 80 mg capsules Ingrezza Sprinkle: 40, 60, 80 mg capsules	Tablets: 6, 9, and 12 mg XR (extended-release) 6, 9 and 24 mg
Other indications	Chorea associated with Huntington’s disease	Chorea associated with Huntington’s disease
Contraindications relevant to TD	None	Hepatic impairment, use of reserpine, MAOIs, tetrabenazine or valbenazine
Warnings and precaution contained in Highlights of Prescribing Information	Somnolence; QT interval prolongation	QT interval prolongation; neuroleptic malignant syndrome; akathisia, agitation, restlessness, and parkinsonism (latter not applicable to TD); sedation/somnolence
Dosing frequency	Once daily	Twice daily (IR) Once daily (XR)
Recommended dosing	Take with or without food; start at 40 mg daily; increase to 80 mg daily after one week as indicated and tolerated. Titration to 60 mg daily after one week of 40 mg, then further titration to 80 mg as indicated may be considered. A therapeutic dosage of 40 mg or 60 mg once daily may be appropriate based on patient’s clinical response and tolerability.	Take 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 metabolizers	Maximum recommended dose is 40 mg/ day	Maximum recommended dose is 36 mg/day
Hepatic impairment	Moderate-to-severe hepatic impairment: maximum recommended dose is 40 mg/day	Contraindicated
Renal impairment	Dosage adjustments are not necessary for patients with mild, moderate, or severe renal impairment	Package insert does not provide any recommendations (cites a lack of studies in this population), but the metabolites are excreted renally
Drug-drug interactions	Valbenazine 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 recommendation	If the patient is at increased risk for QT prolongation, assess QT interval before increasing the dose	If the patient is at increased risk for QT prolongation, assess QT interval before and after increasing the dose above 24 mg/day

References:

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders-Text Revision. 5th ed. Arlington, VA: American Psychiatric Association; 2022.
2. Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Psychiatry. 1988;39(11):1172-1177.
3. Madubueze N, Hammonds LS, Lindfors E. Implementing the Abnormal Involuntary Movement Scale AIMS as an evidence based practice screening tool in adult patients taking antipsychotics to detect and treat tardive dyskinesia. J Psychiatry. 2019;22(1):1-7.
4. Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020;81(2):19cs12983.
5. 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
6. 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
7. Touma, K. T. B., & Scarff, J. R. (2018). Valbenazine and Deutetrabenazine for Tardive Dyskinesia. Innovations in clinical neuroscience, 15(5-6), 13–16.
8. Ingrezza and Ingrezza Sprinkle (valbenazine) capsules package insert. San Diego, CA: Neurocrine Biosciences, Inc.; 2024 Apr.
9. Austedo and Austedo XR (deutetrabenazine) tablets package insert. Parsippany, NJ: Teva Neuroscience, Inc.; 2023 Feb

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