TREATMENT APPROACHES

Inappropriate Anticholinergic Use In Tardive Dyskinesia (TD)

Key Differences in Pharmacologic Effect of Common Treatment Strategies for TD1

Anticholinergics block acetylcholine receptors in the central and autonomic nervous system, and are used to treat a variety of conditions

Anticholinergics may be considered to treat acute dystonia and DIP

Benztropine Prescribing Information2

“In treating acute drug-induced extrapyramidal disorders, after one or two weeks the drug should be withdrawn to determine continued need for it”
“Antiparkinsonism agents do not alleviate the symptoms of TD and in some instances may aggravate them”

“Benztropine is not recommended for use in patients with TD”​

Benztropine in Guidelines

American Academy of Neurology (AAN)

American Psychiatric Association (APA)

American Academy of Neurology (AAN)

2013 AAN Evidence-Based Guidelines3:
  • No controlled trials examining the efficacy of benztropine, biperiden, chlorprothixene, and trihexyphenidyl in treating TD
  • Insufficient data to determine the effectiveness of anticholinergics for the treatment of TD (Level U)

American Psychiatric Association (APA)

2022 APA DSM-5-TR: Medication Induced Movement Disorders4:
The symptoms of tardive dyskinesia tend to be worsened by stimulants, antipsychotic medication withdrawal, and anticholinergic medications (such as benztropine) and may be transiently worsened by emotional arousal, stress, and distraction during voluntary movements in unaffected parts of the body

The need for anticholinergic medication(s) should be reconsidered regularly to reduce anticholinergic burden5

American Geriatric Society’s Beers Criteria6

What are the AGS Beers Criteria?

An explicit list of potentially inappropriate medications that are best avoided by adults aged ≥ 65 years old

What is the Purpose of the AGS Beers Criteria?

Improve medication selection
Educate clinicians and patients
Reduce adverse drug events
Benztropine (oral) and trihexyphenidyl are not recommended in older adults for prevention or treatment of extrapyramidal symptoms associated with antipsychotics according to the AGS Beers Criteria®

Tardive Dyskinesia

Defined as abnormal, involuntary movements of the tongue, jaw, trunk, or extremities that develop in association with medications that block post-synaptic dopamine receptors.7
Tardive Dyskinesia is caused by upregulation and subsequent hypersensitivity of brain dopamine D2 receptors following prolonged exposure to Dopamine Receptor Blocking Agents (DRBAs), such as antipsychotics.8

VMAT 2 Inhibitors Recommended by APA Clinical Guidelines9

Reversible VMAT2 inhibitors are recommended in patients with moderate to severe or disabling TD

VMAT2 inhibitors can also be considered for patients with mild TD

There is insufficient evidence to support a guideline statement on the use of the following treatments in individuals with TD:

Anticholinergics (e.g., benztropine)

Benzodiazepines (e.g., clonazepam)

Change in antipsychotic therapy to a lower-potency medication

Ginkgo biloba

Cessation or reduction of antipsychotic medication

Amantadine

Vitamin E

For Medical Information Only.

Up Next
Rethinking the Use of Anticholinergics in Older Adults Diagnosed with Tardive Dyskinesia
Tune in as Jennifer Mondillo, a gerontology nurse practitioner, and Rob Leffler, a board-certified geriatric pharmacist, explain the inappropriate use of anticholinergic medications to treat older adults with tardive dyskinesia (TD), a drug-induced movement disorder. These experts emphasize the importance of reducing or eliminating the anticholinergic burden in patients with TD and discuss practical approaches to evaluating anticholinergic use in LTC residents with drug-induced movement disorders, de-prescribing, and treating TD appropriately with VMAT2 inhibitors.
This podcast has been sponsored and co-developed by Neurocrine Biosciences, Inc. This podcast is for educational purposes only and is not intended to promote any specific product. The speakers are presenting on behalf of and are paid consultants for Neurocrine Biosciences. The information provided herein is based upon the healthcare provider’s clinical judgement and personal experience.
Up Next
EXPLORE OUR FOCUS ON VMAT2 INHIBITORS PATH
Want to learn more about treating tardive dyskinesia? Follow this path to learn about the mechanism of action and pharmacology of VMAT2 inhibitors.
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a) Dopamine Receptor Blocking Agent

References
1. Hauser RA, Meyer JM, Factor SA, Comella CL, Tanner CM, Xavier RM, Caroff SN, Lundt L. Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice. CNS Spectr. 2022 Apr;27(2):208-217. doi: 10.1017/S109285292000200X. Epub 2020 Nov 20. PMID: 33213556; PMCID: PMC9249122.
2. Benztropine mesylate [package insert]. Warren, NJ: Cipla USA, Inc.; 2020.
3. Bhidayasiri R, et al. Neurology. 2013;81(5):463-469.
4. APA: DSM-5-TR. Washington, DC. 2022.
5. Vanegas-Arroyave, N., Caroff, S.N., Citrome, L. et al. An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders. CNS Drugs 38, 239–254 (2024).
6. 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. J Am Geriatr Soc. 2023;2023(71):2052–81.
7. American Psychiatric Association: Diagnostic and Stat Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition – Text Revision. American Psychiatric
Association: Washington, DC; 2022
8. Klawans H, et al. Acta Neurol Scand. 1970;46(4):409-441.
9. American Psychiatric Association. Clinical Practice Guidelines for Treatment of Patients with Schizophrenia. Accessed on November 8, 2020. 
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Your Resources on Tardive Dyskinesia and Other DIMDs

These free educational resources are sponsored and developed by Neurocrine Biosciences, Inc.
Discover TD®
In this interactive application, users can differentially diagnose and develop appropriate management plans for hypothetical, virtual patients with various movement disorders.
DIMD Course
Enroll in this free, virtual self-paced learning platform delving into various clinical aspects of the most common DRBA-induced movement disorders and earn a recognized certificate of completion. 

Media Platforms

TD Dialogues® Podcast
Hear from experts in insightful conversations as they discuss the challenges of recognizing TD and share real-world strategies to effectively support patients in managing symptoms.
Neurocrine Medical: Brave Science™ YouTube Channel
This channel features educational videos designed to further understanding of TD, including content on the proposed mechanism of disease in TD and differentiating TD from drug-induced parkinsonism.

Explore the DIMD Ecosystem Library

Want to explore our collection of DIMD educational resources on your own? Use the link below to view the full content library.
This educational content was sponsored and developed by Neurocrine Biosciences, Inc. This non-CME program is intended to provide general information about drug-induced movement disorders and not medical advice for any particular patient.

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