What medications are recommended for treating agitation in dementia?

Medications for Agitation in Dementia

Non-pharmacological interventions should be implemented as first-line management for agitation in dementia, with pharmacological options reserved for when these approaches are insufficient, with atypical antipsychotics being the appropriate first-line pharmacological treatment for severe behavioral symptoms with psychotic features. 1

Treatment Algorithm

Step 1: Non-Pharmacological Approaches (First-Line)

• Identify and address underlying causes through:
  • Screening for pain, medical conditions, medication side effects
  • Investigating sensory deficits, dehydration, fecal impaction
  • Documenting triggers using ABC (antecedent-behavior-consequences) charting
• Implement environmental modifications:
  • Create predictable daily routines
  • Ensure adequate lighting and clear signage
  • Reduce noise and sensory overload
  • Provide comfortable seating and access to necessities
• Use structured activities and distraction techniques
• Provide caregiver education and support

Step 2: Pharmacological Interventions (When Non-Pharmacological Approaches Fail)

First-Line Pharmacological Options:

1. Cholinesterase inhibitors for mild-moderate agitation 1
2. Atypical antipsychotics for severe agitation with psychotic features 1
   • Brexpiprazole - specifically approved for agitation in Alzheimer's dementia
   • Quetiapine - preferred for agitation in Lewy Body Dementia
   • Use lowest effective dose for shortest duration possible

Second-Line Options:

• Trazodone: Initial dose 25 mg/day, maximum 200-400 mg/day 1
• Gabapentin: For behavioral and psychological symptoms of dementia 1

For Acute Severe Agitation:

• Haloperidol: 0.5-1 mg orally at night and every 2 hours when required (max 5 mg daily in elderly) 1
• Lorazepam: 0.25-0.5 mg orally four times daily as required (max 2 mg/24 hours) 1
• Midazolam: 2.5-5 mg subcutaneously every 2-4 hours as required (reduced to 5 mg/24 hours if eGFR <30 mL/min) 1

Important Considerations and Cautions

Black Box Warning

Antipsychotics carry a black box warning for increased mortality in elderly patients with dementia-related psychosis 2. The FDA label for olanzapine explicitly includes this warning, indicating significant risk.

Monitoring Requirements

• Assess effectiveness using quantitative measures like the Neuropsychiatric Inventory Questionnaire (NPI-Q)
• Monitor for medication side effects, particularly:
  • Extrapyramidal symptoms
  • Somnolence
  • Cardiovascular effects
• Reassess at least every 6 months
• Attempt medication tapering after 6 months of symptom stabilization 1

Medication-Specific Considerations

• Atypical antipsychotics probably reduce agitation slightly (moderate-certainty evidence) but have a negligible effect on psychosis (moderate-certainty evidence) 3
• These medications increase risk of somnolence, extrapyramidal symptoms, and serious adverse events 3
• The apparent effectiveness seen in practice may partly reflect the natural course of symptoms, as observed in placebo groups 3

Practical Approach to Medication Selection

1. For patients with Lewy Body Dementia: Quetiapine is preferred due to lower risk of extrapyramidal symptoms 1
2. For Alzheimer's dementia with agitation: Brexpiprazole has specific indication 1
3. For patients at high risk of EPS: Consider risperidone at low doses (mean effective dose ~1.0 mg/day) 4
4. For nighttime agitation ("sundowning"): Trazodone may be particularly effective 5

Remember that combination pharmacotherapy should only be considered after failed trials with two different classes of agents at sufficient doses 1. The goal should always be to use the lowest effective dose for the shortest duration possible to minimize adverse effects while managing symptoms effectively.