What non‑antipsychotic pharmacologic and non‑pharmacologic options are available for managing agitation in patients with dementia?

Non-Antipsychotic Options for Dementia-Related Agitation

For dementia-related agitation, SSRIs (citalopram 10-40 mg/day or sertraline 25-200 mg/day) are the preferred first-line pharmacological option after non-pharmacological interventions have been attempted, with trazodone 25-200 mg/day as a second-line alternative, while antipsychotics should be reserved only for severe, dangerous agitation threatening substantial harm to self or others. 1

Step 1: Address Reversible Medical Causes First

Before any medication, systematically investigate and treat underlying triggers that commonly drive agitation in dementia patients who cannot verbally communicate discomfort 1:

• Pain assessment and management - the single most important contributor to behavioral disturbances 1
• Infections - particularly urinary tract infections and pneumonia 1
• Metabolic disturbances - hypoxia, dehydration, electrolyte abnormalities, hyperglycemia 1
• Constipation and urinary retention - both significantly contribute to restlessness 1
• Medication review - identify and discontinue anticholinergic medications (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen agitation 1

Step 2: Implement Non-Pharmacological Interventions

These must be attempted and documented as failed before considering medications 1:

Environmental Modifications

• Ensure adequate lighting and reduce excessive noise 1
• Simplify environment with clear labels and structured layouts 1
• Establish predictable daily routines for meals, exercise, and sleep 1
• Increase daytime bright light exposure (2 hours of morning bright light at 3,000-5,000 lux) to reduce sundowning 1

Communication Strategies

• Use calm tones and simple one-step commands instead of complex multi-step instructions 1
• Allow adequate time for the patient to process information before expecting response 1
• Use gentle touch for reassurance 1

Activity-Based Interventions

• Music therapy - most effective non-pharmacological intervention for reducing agitation 2
• Structured individualized activities matching current abilities and past interests 1
• At least 30 minutes of supervised physical activity and sunlight exposure daily 1

Step 3: First-Line Pharmacological Treatment - SSRIs

When to initiate: Only after non-pharmacological interventions have been systematically attempted for 24-48 hours and documented as insufficient, and the patient has chronic agitation without psychotic features 1

Preferred Options

Citalopram 1:

• Start: 10 mg/day
• Maximum: 40 mg/day
• Well-tolerated, though some patients experience nausea and sleep disturbances
• Critical warning: Monitor for QT prolongation 3

Sertraline 1:

• Start: 25-50 mg/day
• Maximum: 200 mg/day
• Well-tolerated with less effect on metabolism of other medications
• Significantly improves overall neuropsychiatric symptoms, agitation, and depression in vascular dementia 1

Monitoring

• Assess response using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) within 4 weeks 1
• If no clinically significant response after 4 weeks at adequate dose, taper and withdraw 1
• Even with positive response, periodically reassess need for continued medication 1

Step 4: Second-Line Pharmacological Treatment - Trazodone

When to consider: If SSRIs have failed or are not tolerated 1

Trazodone dosing 1:

• Start: 25 mg/day
• Maximum: 200-400 mg/day in divided doses
• Caution: Use carefully in patients with premature ventricular contractions due to risk of orthostatic hypotension
• Safer alternative to antipsychotics with better tolerability profile 1

Step 5: Alternative Options (Limited Evidence)

Memantine

• May be helpful for agitation in Alzheimer's disease patients already on acetylcholinesterase inhibitors 4
• Should be initiated to enhance cognition if not already prescribed 3

Carbamazepine

• Preliminary evidence suggests potential benefit 4
• Not extensively studied in placebo-controlled trials in dementia patients 5

What NOT to Use

Benzodiazepines

Avoid for routine agitation management (except alcohol/benzodiazepine withdrawal) 1:

• Increase delirium incidence and duration 1
• Cause paradoxical agitation in approximately 10% of elderly patients 1
• Risk of tolerance, addiction, cognitive impairment, respiratory depression, and falls 1

Anticholinergic Medications

• Diphenhydramine, hydroxyzine, oxybutynin, cyclobenzaprine worsen confusion and agitation 1
• Should be identified and discontinued 1

When Antipsychotics Are Necessary

Reserve only for: Severe agitation with imminent risk of harm to self or others after behavioral interventions have failed 1

Critical safety discussion required before initiation 1:

• Increased mortality risk (1.6-1.7 times higher than placebo)
• Cardiovascular effects including QT prolongation, sudden death, stroke risk
• Falls, hypotension, metabolic changes
• Use lowest effective dose for shortest duration possible
• Daily in-person evaluation required
• Attempt taper within 3-6 months

Special Considerations

Vascular Dementia

• SSRIs are explicitly designated as first-line pharmacological treatment 1
• Avoid risperidone and olanzapine due to three-fold increase in stroke risk 1

Sundowning

• Increase morning bright light exposure (2 hours at 3,000-5,000 lux) 1
• Avoid bright light in evening 1
• Increase daytime physical and social activities 1
• Establish structured bedtime routine 1

Common Pitfalls to Avoid

• Do not add medications without first treating reversible medical causes 1
• Do not use antipsychotics for mild agitation or behaviors like unfriendliness, poor self-care, repetitive questioning, or wandering 1
• Do not continue medications indefinitely - review need at every visit 1
• Do not rely solely on pharmacological interventions without non-pharmacological strategies 6
• Do not underestimate the role of pain as a cause of behavioral disturbances 6