What is the recommended treatment for agitation and anxiety in patients with dementia?

Treatment of Agitation and Anxiety in Dementia

For agitation and anxiety in dementia, implement non-pharmacological interventions first, then use trazodone (starting at 25 mg/day) as the safest first-line medication option, reserving antipsychotics only for severe, dangerous symptoms that fail behavioral approaches. 1

Initial Assessment and Non-Pharmacological Management

Before any medication, systematically assess and address modifiable contributors:

• Evaluate for pain, which is often undertreated and frequently manifests as agitation in patients who cannot verbally communicate discomfort 1, 2
• Assess the type, frequency, severity, pattern, and timing of symptoms using quantitative measures such as the Cohen-Mansfield Agitation Inventory or Neuropsychiatric Inventory Questionnaire 3
• Rule out medical causes including urinary tract infections, constipation, dehydration, pneumonia, medication side effects (especially anticholinergic drugs), and sensory impairments 4

Implement person-centered non-pharmacological interventions:

• Provide environmental modifications including adequate lighting, reduced noise, structured daily routines, and meaningful activities tailored to the patient's interests 1, 2
• Use effective communication with calm tones, simple one-step commands, gentle touch for reassurance, and allow adequate time for processing information 4
• Ensure adequate supervision and environmental safety, including removal of hazardous items 1

Pharmacological Treatment Algorithm

For Mild to Moderate Agitation/Anxiety

First-line: Trazodone

• Start at 25 mg per day, titrate to maximum 200-400 mg per day in divided doses 3, 1
• Trazodone is the safest first-line option due to better tolerability than antipsychotics or mood stabilizers 1
• Use with caution in patients with premature ventricular contractions 3, 1

Second-line: SSRIs (for chronic agitation)

• Sertraline 25-50 mg per day (maximum 200 mg per day) - well tolerated with less effect on metabolism of other medications 3
• Citalopram 10 mg per day (maximum 40 mg per day) - well tolerated though some patients experience nausea and sleep disturbances 3
• Allow 4-8 weeks for full therapeutic trial before assessing response 3

Third-line: Divalproex sodium (mood stabilizer)

• Start at 125 mg twice daily, titrate to therapeutic blood level (40-90 mcg/mL) 3, 1
• Generally better tolerated than other mood stabilizers 3
• Monitor liver enzyme levels, platelets, prothrombin time, and partial thromboplastin time 3, 1

For Severe Agitation with Psychotic Features

Antipsychotics should only be used when:

• Symptoms are severe, dangerous, and/or cause significant distress to the patient 3
• The patient is threatening substantial harm to self or others 3, 4
• Non-pharmacological interventions have been reviewed and failed 3

Before initiating antipsychotics, discuss with patient (if feasible) and surrogate decision maker:

• Increased mortality risk (particularly in patients over 75 years) 3, 4
• Cardiovascular effects, cerebrovascular adverse reactions, falls risk, and metabolic changes 3, 4
• Expected benefits, treatment goals, and plans for ongoing monitoring 3, 4

Atypical antipsychotic options (in order of preference):

• Risperidone: Start at 0.25 mg at bedtime, maximum 2-3 mg per day in divided doses; potential extrapyramidal symptoms at 2 mg per day 3
• Quetiapine: Start at 12.5 mg twice daily, maximum 200 mg twice daily; more sedating with risk of transient orthostasis 3, 2
• Olanzapine: Start at 2.5 mg at bedtime, maximum 10 mg per day; generally well tolerated but less effective in patients over 75 years 3, 4

Initiate at low dose and titrate to minimum effective dose as tolerated 3

Medications to Avoid

Benzodiazepines should be avoided due to:

• Risk of tolerance, addiction, depression, and cognitive impairment 3, 1
• Paradoxical agitation occurs in approximately 10% of elderly patients 3, 1
• Can increase delirium incidence and duration 4

Typical antipsychotics (haloperidol, fluphenazine, thiothixene) should be avoided as first-line therapy:

• Associated with 50% risk of irreversible tardive dyskinesia after 2 years of continuous use in elderly patients 3, 1
• Significant extrapyramidal symptoms and severe anticholinergic, cardiovascular effects 3

Monitoring and Reassessment

Assess response to treatment using quantitative measures:

• If no clinically significant response after 4 weeks of adequate dosing, taper and withdraw the medication 3, 1
• If significant side effects develop, review the risk/benefit balance and determine if tapering and discontinuing is indicated 3

For patients who respond positively:

• Periodically reassess the need for continued medication at every visit 3, 4
• Avoid inadvertent chronic use of antipsychotics - approximately 47% of patients continue receiving them after discharge without clear indication 4
• After 9 months, use dosage reduction to reassess the need to medicate 3

Common Pitfalls to Avoid

• Do not use antipsychotics for mild agitation - reserve them only for severe, dangerous symptoms 3, 4
• Do not skip non-pharmacological interventions unless in an emergency situation with imminent risk of harm 3, 4
• Do not continue antipsychotics indefinitely - the benefits are modest at best (SMD -0.21) and must be weighed against mortality risks 2
• Do not use typical antipsychotics as first-line due to the high risk of tardive dyskinesia and extrapyramidal symptoms 3, 1