What are the safety considerations for using Abilify (aripiprazole) in older adults?

Safety Considerations for Abilify (Aripiprazole) in Older Adults

Aripiprazole should be avoided in older adults with dementia-related psychosis due to increased mortality risk, and used with extreme caution in other older adults only when absolutely necessary, starting at very low doses (2.5-5mg) with careful monitoring.

Boxed Warning and Mortality Risk

• Elderly patients with dementia-related psychosis treated with antipsychotics, including aripiprazole, have an increased risk of death 1
• Aripiprazole is NOT FDA-approved for the treatment of patients with dementia-related psychosis 1
• In placebo-controlled studies of aripiprazole in elderly patients with psychosis associated with Alzheimer's disease, there was an increased incidence of cerebrovascular adverse events, including fatalities 1

Adverse Effects in Older Adults

• Common adverse reactions in elderly patients (incidence ≥3% and at least twice that of placebo) include:

  • Lethargy (5% vs 2% for placebo) 1
  • Somnolence/sedation (8% vs 3% for placebo) 1
  • Urinary incontinence (5% vs 1% for placebo) 1
  • Excessive salivation (4% vs 0% for placebo) 1
  • Lightheadedness (4% vs 1% for placebo) 1

• Additional risks include:

  • Increased risk of cerebrovascular adverse events (stroke, TIA) with a dose-dependent relationship 1
  • Difficulty swallowing or excessive somnolence that could lead to injury or aspiration 1

Dosing Considerations

• If aripiprazole must be used in older adults (for non-dementia indications), start at much lower doses than used in younger adults 2
• The recommended starting dose should be significantly reduced from standard adult dosing 2
• Allow at least 1-2 weeks, sometimes up to 4 weeks, before assessing full effect of aripiprazole 3
• Steady-state concentrations are attained within 14 days of dosing 3

Comparison to Other Antipsychotics

• Among antipsychotics, aripiprazole is described as "less likely to cause extrapyramidal symptoms (EPS)" compared to typical antipsychotics, but requires careful dosing and has more potential drug interactions 2
• In the EPS risk hierarchy for elderly patients, aripiprazole has moderate risk, higher than quetiapine (which has the lowest risk) but lower than risperidone and typical antipsychotics 2
• Aripiprazole has a more favorable metabolic and cardiovascular profile compared to some other atypical antipsychotics 4

Monitoring Recommendations

• Monitor for:
  • Orthostatic hypotension, especially during initial dose titration 2
  • Sedation and somnolence 1
  • Difficulty swallowing 1
  • Extrapyramidal symptoms 2
  • Cardiovascular effects 1

Beers Criteria Recommendations

• The American Geriatrics Society Beers Criteria® identifies antipsychotics as potentially inappropriate medications in older adults 5
• Antipsychotics should be avoided in older adults due to the risk of increased mortality 5
• The use of these medications can cause substantial harm in older adults, including worsening heart failure, hypotension, and delirium 5

Drug Interactions of Concern

• Avoid combining aripiprazole with:
  • Benzodiazepines (increased sedation risk) 2
  • Other CNS depressants 5
  • The concurrent use of a combination of three or more central nervous system agents (antidepressants, antipsychotics, benzodiazepines, nonbenzodiazepine hypnotics, antiepileptics, and opioids) increases fall risk 5

Clinical Practice Recommendations

• Aripiprazole should only be used in selected patient populations resistant to non-pharmacological treatment with persisting or severe symptoms 6
• The indication for continuing treatment should be revised regularly 6
• Behavioral interventions should be tried before pharmacological treatment whenever possible 2
• If an antipsychotic is deemed necessary, consider quetiapine as an alternative with lower EPS risk in older adults 2