Tardive Dyskinesia Overview in Adults and Elderly US 2025

Description and Characteristics of Tardive Dyskinesia

Tardive dyskinesia is a hyperkinetic movement disorder associated with prolonged use of dopamine receptor blocking agents. It presents as involuntary, repetitive movements, commonly including:

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

Symptoms often develop after months or years of treatment with dopamine antagonists and may continue after discontinuation of these medications. TD mainly occurs in patients treated for neuropsychiatric disorders such as schizophrenia, schizoaffective disorder, bipolar disorder, or mood disorders, but it may also affect individuals with developmental disabilities or brain disorders following limited exposure.

Risk Factors and Prevalence in Elderly Populations

Age is an important risk factor for TD, with elderly adults (65 years and older) showing increased rates compared to younger adults. Research indicates:

• Around 29% of elderly patients on dopamine antagonist treatment for three months may develop TD.
• Longer-term use is associated with prevalence ranging approximately from 26% to 67% among elderly patients.
• Adults aged 60 and older sometimes develop symptoms after as little as one month of exposure to these medications.
• Some studies suggest elderly females may have higher susceptibility.
• Certain populations, including African and African American individuals, may have increased vulnerability following low-dose or short-duration exposure.
• Smoking is also linked to elevated risk.

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

Underlying Mechanisms and Genetic Contributions

The exact mechanisms of TD are not fully defined but generally involve:

• Dopamine Receptor Supersensitivity: Extended blockade of dopamine D2 receptors in the basal ganglia can lead to compensatory receptor changes and increased sensitivity.
• Altered Dopamine Signaling: Resulting receptor hypersensitivity contributes to abnormal hyperkinetic movements.
• Other dopamine receptors, such as D3, D4, and D5, may also be involved.
• Genetic variations in dopamine receptor genes (DRD2, DRD3), serotonin receptor genes (5-HT2A, 5-HT2C), and brain-derived neurotrophic factor (BDNF) gene variants might affect individual susceptibility.
• Oxidative stress and neurodegenerative factors, like lipid peroxidation, may contribute.

While genetics may play a role, their specific impact in elderly populations requires further study.

Medications Associated with Tardive Dyskinesia

Medications commonly linked to TD include:

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

Risk is influenced by drug potency, dosage, duration of exposure, and patient-specific sensitivity.

Clinical Features and Impact in Adults and Elderly Patients

Common clinical signs include:

• Orofacial Dyskinesias: Tongue thrusting, lip smacking, puckering, chewing motions.
• Peripheral Movements: Involuntary movements of limbs and trunk which can affect mobility and balance.
• Functional Effects: Difficulties with eating, swallowing, and potential respiratory or dental issues.
• Impact on Quality of Life: Symptoms may lead to social withdrawal, isolation, increased caregiver demands, and diminished quality of life, particularly in elderly individuals.

Movement symptoms may vary in severity and sometimes become persistent.

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 soon after starting dopamine antagonists and commonly improve with dosage adjustments.
• Psychogenic or non-organic movements: Characterized by inconsistent patterns not explained by neurological causes.
• Withdrawal dyskinesias: Movement symptoms that occur temporarily after cessation of dopamine antagonists.

Diagnosis involves clinical evaluation, patient history, and exclusion of alternative explanations.

Treatment Developments: Valbenazine Use in Elderly Patients

Valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved by the FDA for TD treatment and has clinical trial data supporting its use in elderly patients. Findings from long-term studies include:

• Efficacy:
  • Reduction in TD symptoms was observed, measured by changes in Abnormal Involuntary Movement Scale (AIMS) scores.
  • A substantial proportion of elderly patients experienced improvements of 30% or more on AIMS after 48 weeks.
  • Clinical Global Impression of Change (CGI-TD) ratings indicated many participants showed perceived improvements.
• Safety:
  • Valbenazine was generally well tolerated in adults aged 65 and older.
  • Commonly reported side effects included urinary tract infections and somnolence, occurring in approximately 10.9% of patients.
  • No significant destabilization of psychiatric symptoms was reported during treatment.
• Dosing and Administration:
  • Administered once daily with no required elderly-specific dose adjustments.
  • Available in capsule forms, including sprinkle formulations for those with swallowing difficulties.
  • Typical doses are 40 mg or 80 mg daily, with some evidence suggesting higher doses may provide better symptom control.
• Clinical Considerations:
  • Use under medical supervision is recommended, with monitoring for sedation or potential worsening of movements.

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

Approaches to Patient Management and Education

Management strategies include:

• Patient and Caregiver Education:
  • Providing information about TD risks related to dopamine antagonist use.
  • Discussing the potential benefits and side effects of ongoing treatments.
• Monitoring:
  • Regular evaluation for movement symptoms using standardized assessments such as AIMS.
  • Early detection of signs encourages timely management.
• Treatment Planning:
  • Carefully considering dosage adjustments or discontinuation of offending agents when possible.
  • Considering VMAT2 inhibitors like valbenazine for symptom control if appropriate.
• Safety Measures:
  • Avoidance of dopamine receptor blocking drugs when feasible.
  • Use of medical alert devices can help prevent inadvertent medication exposures.
• Support and Quality of Life:
  • Addressing social factors and caregiver needs.
  • Multidisciplinary care approaches may improve overall patient well-being.

Tardive dyskinesia remains an important clinical challenge in adults and elderly patients due to increased susceptibility in older age and potential impact on function and quality of life. It is a persistent movement disorder primarily resulting from dopamine receptor blocking treatments. Current treatment options, including valbenazine, provide symptom management possibilities that have been studied in elderly populations, showing efficacy and tolerability. Ongoing research and attentive clinical monitoring are essential to improve care for individuals 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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