Tardive Dyskinesia Overview in Adults and Elderly US 2025

Description and Characteristics of Tardive Dyskinesia

Tardive dyskinesia is a hyperkinetic movement disorder linked to long-term use of dopamine receptor blocking agents. It manifests as involuntary, repetitive movements, commonly including:

• Orofacial movements such as tongue protrusion, lip smacking, and chewing
• Facial grimacing
• Movements involving the trunk and limbs

Symptoms usually develop after months or years of dopamine antagonist treatment and may persist after stopping these medications. TD primarily occurs in patients treated for neuropsychiatric disorders such as schizophrenia, schizoaffective disorder, bipolar disorder, or mood disorders, but it can also affect individuals with developmental disabilities or brain disorders following limited exposure.

Risk Factors and Prevalence in Elderly Populations

Age is a significant risk factor for TD, with elderly adults (65 years and older) demonstrating higher rates compared to younger adults. Research shows:

• Approximately 29% of elderly patients on dopamine antagonist therapy for three months may develop TD.
• Longer-term use is linked to prevalence rates ranging roughly from 26% to 67% among elderly patients.
• Adults aged 60 and older sometimes develop symptoms after as little as one month of drug exposure.
• Some evidence indicates elderly females may be more susceptible.
• Certain groups, including African and African American populations, may exhibit increased vulnerability after low-dose or short-term exposure.
• Smoking is also associated with higher risk.

These factors likely relate to age-associated changes in dopamine receptor sensitivity, variations in drug metabolism, and possible genetic influences.

Underlying Mechanisms and Genetic Contributions

The precise mechanisms of TD are not completely understood but generally include:

• Dopamine Receptor Supersensitivity: Prolonged blockade of dopamine D2 receptors in the basal ganglia can cause compensatory receptor changes and increased sensitivity.
• Altered Dopamine Signaling: Subsequent receptor hypersensitivity contributes to abnormal hyperkinetic movements.
• Additional dopamine receptors, such as D3, D4, and D5, may also be implicated.
• Genetic variants in dopamine receptor genes (DRD2, DRD3), serotonin receptor genes (5-HT2A, 5-HT2C), and brain-derived neurotrophic factor (BDNF) gene variants might influence individual susceptibility.
• Oxidative stress and neurodegenerative factors, including lipid peroxidation, may play a role.

While genetics may be contributory, their precise impact in elderly populations calls for further investigation.

Medications Associated with Tardive Dyskinesia

Drugs commonly linked to TD include:

• First-generation (typical) antipsychotics: High-potency agents like haloperidol, droperidol, fluphenazine
• Second-generation (atypical) antipsychotics: Such as olanzapine, risperidone, paliperidone, and amisulpride, which carry a lower but existent risk.
• Other dopamine antagonists: Metoclopramide and prochlorperazine, with considerable risk especially in elderly patients.
• Additional medications: Certain antidepressants like fluoxetine and amoxapine, antihistamines, and anticholinergics may also be implicated.

Risk depends on drug potency, dosage, duration of use, and patient-specific sensitivity.

Clinical Features and Impact in Adults and Elderly Patients

Typical clinical signs include:

• Orofacial Dyskinesias: Tongue thrusting, lip smacking, puckering, chewing movements.
• Peripheral Movements: Involuntary motions of limbs and trunk which can impair mobility and balance.
• Functional Effects: Challenges with eating, swallowing, and potential respiratory or dental complications.
• Impact on Quality of Life: Symptoms may cause social withdrawal, isolation, increased caregiver burden, and reduced quality of life, especially in elderly individuals.

Movement symptoms vary in severity and can sometimes become chronic.

Distinguishing TD from Other Movement Disorders

TD is differentiated from other conditions such as:

• Acute extrapyramidal symptoms (EPS): Including acute dystonia, akathisia, and parkinsonism, which often appear shortly after starting dopamine antagonists and typically improve with dosage adjustments.
• Psychogenic or non-organic movements: Characterized by inconsistent patterns unexplained by neurological causes.
• Withdrawal dyskinesias: Movement symptoms occurring temporarily after cessation of dopamine antagonists.

Diagnosis involves clinical examination, patient history, and ruling out alternative causes.

Treatment Developments: Valbenazine Use in Elderly Patients

Valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for TD treatment and has clinical trial data supporting its use in elderly patients. Long-term study findings include:

• Efficacy:
  • Reduction in TD symptoms was recorded via changes in Abnormal Involuntary Movement Scale (AIMS) scores.
  • A significant proportion of elderly patients showed improvements of 30% or more on AIMS after 48 weeks.
  • Clinical Global Impression of Change (CGI-TD) ratings reflected perceived patient improvement.
• Safety:
  • Valbenazine was generally well tolerated in adults aged 65 and older.
  • Common side effects included urinary tract infections and somnolence, occurring in about 10.9% of patients.
  • No notable destabilization of psychiatric symptoms occurred during treatment.
• Dosing and Administration:
  • Administered once daily without requiring dose adjustments specific to elderly patients.
  • Available in capsule forms, including sprinkle formulations suitable for those with swallowing difficulties.
  • Typical dosages are 40 mg or 80 mg daily, with data suggesting higher doses may yield better symptom control.
• Clinical Considerations:
  • Use under medical supervision is advised, with monitoring for sedation or potential worsening of movements.

Valbenazine provides an additional option for symptom management in elderly patients with TD.

Approaches to Patient Management and Education

Management approaches include:

• Patient and Caregiver Education:
  • Offering information about TD risks linked to dopamine antagonist use.
  • Discussing possible benefits and side effects of ongoing therapies.
• Monitoring:
  • Regular assessment for movement symptoms using standardized tools such as AIMS.
  • Early detection facilitates timely intervention.
• Treatment Planning:
  • Careful consideration of dosage reductions or cessation of offending agents when feasible.
  • Considering VMAT2 inhibitors like valbenazine for symptom control if appropriate.
• Safety Measures:
  • Avoiding dopamine receptor blocking drugs when possible.
  • Employing medical alert devices to help prevent accidental medication exposures.
• Support and Quality of Life:
  • Addressing social factors and caregiver support needs.
  • Multidisciplinary care models may enhance overall patient well-being.

Conclusion

Tardive dyskinesia remains a significant clinical challenge in adults and elderly patients due to heightened vulnerability with advancing age and its potential effects on function and quality of life. It is a persistent movement disorder mainly resulting from dopamine receptor blocking treatments. Current therapeutic options, including valbenazine, offer symptom management choices that have been evaluated in elderly populations, demonstrating efficacy and tolerability. Continued research and vigilant clinical monitoring are critical to improving care for those affected by TD.

Sources

1. eMedicine Medscape: Tardive Dyskinesia Overview
2. Journal of Clinical Psychiatry 2025: Improvements Over Time with Valbenazine in Elderly Adults with TD
3. PR Newswire 2025: Neurocrine Biosciences on Valbenazine in Older Adults with TD

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