What is the first line treatment for agitation in dementia?

First-Line Treatment for Agitation in Dementia

Non-pharmacological, person-centered interventions are the mandatory first-line treatment for agitation in dementia, and medications should only be considered after these behavioral approaches have been adequately trialed and failed, or in emergency situations with imminent risk of harm. 1, 2

Initial Assessment Before Any Treatment

Before implementing any intervention, you must:

• Evaluate and treat underlying medical causes, particularly pain (often undertreated and manifests as agitation), urinary tract infections, constipation, dehydration, pneumonia, hypoxia, and medication side effects (especially anticholinergic drugs) 1, 2, 3
• Use quantitative measures such as the Cohen-Mansfield Agitation Inventory or Neuropsychiatric Inventory Questionnaire (NPI-Q) to establish baseline severity and monitor treatment response 3
• Review all current medications for drug toxicity or adverse effects that may be worsening agitation 3

Non-Pharmacological Interventions (Mandatory First-Line)

These interventions must be implemented before considering any medication 1, 2:

Environmental Modifications

• Reduce noise levels and ensure appropriate lighting to minimize triggers 2, 3
• Establish predictable daily routines for exercise, meals, and bedtime 2
• Remove hazardous items and install safety features like handrails 3

Person-Centered Behavioral Approaches

• Implement structured, tailored activities individualized to the person's current capabilities and previous interests 2
• Use the "three R's" approach: repeat instructions, reassure the patient, and redirect attention away from problematic situations 2
• Employ effective communication: calm tones, simple one-step commands, gentle touch for reassurance, and allow adequate time for processing 3
• Consider simulated presence therapy using audio/video recordings prepared by family members 2

Evidence-Based Specific Interventions

• Massage therapy, animal-assisted interventions, and personally tailored interventions have the strongest evidence for reducing agitation 2, 4
• Person-centered care and communication skills training decrease symptomatic and severe agitation immediately (effect sizes 0.3-1.8) and for up to 6 months (effect sizes 0.2-2.2) 5
• Music therapy and structured activities by protocol decrease overall agitation with effect sizes of 0.5-0.6 5

When to Consider Pharmacological Treatment

Medications should only be considered when 1, 3:

• Symptoms are severe, dangerous, or causing significant distress
• The patient is threatening substantial harm to self or others
• Non-pharmacological interventions have been adequately trialed and failed
• Emergency situations with imminent risk of harm

First-Line Pharmacological Treatment (When Non-Pharmacological Fails)

SSRIs are the first-line pharmacological treatment for chronic agitation in dementia 2, 3:

Preferred SSRI Options

• Citalopram: Start 10 mg/day, maximum 40 mg/day 2, 3
• Sertraline: Start 25-50 mg/day, maximum 200 mg/day 2, 3

Evidence and Monitoring

• SSRIs significantly reduce overall neuropsychiatric symptoms and agitation in patients with vascular cognitive impairment and dementia 2
• Monitor for side effects: sweating, tremors, nervousness, insomnia/somnolence, dizziness, gastrointestinal disturbances, nausea, and sleep disturbances 2, 3
• Assess response after 4 weeks at adequate dosing; if no clinically significant response, taper and withdraw 2, 3
• Periodically reassess the need for continued medication even with positive response 2, 3

Second-Line Pharmacological Options

For Severe Agitation with Psychotic Features (After SSRI Failure)

Low-dose atypical antipsychotics may be considered only after careful risk-benefit discussion 1, 3:

• Risperidone: Start 0.25 mg at bedtime, maximum 2-3 mg/day in divided doses (extrapyramidal symptoms risk at ≥2 mg/day) 3
• Quetiapine: Start 12.5 mg twice daily, maximum 200 mg twice daily (more sedating, risk of orthostatic hypotension) 3
• Olanzapine: Start 2.5 mg at bedtime, maximum 10 mg/day (less effective in patients >75 years) 3

Critical Antipsychotic Warnings

• Antipsychotics have at best small benefits with modest effect sizes (SMD -0.21,95% CI -0.30 to -0.12) 1
• Increased mortality risk in elderly dementia patients must be discussed with patient/surrogate before initiating 1, 3
• Additional risks include: QT prolongation, sudden death, dysrhythmias, hypotension, pneumonia, falls, metabolic effects, and cerebrovascular adverse reactions 3
• Start at lowest dose, titrate slowly, use for shortest duration possible, and evaluate daily 1, 3
• Approximately 47% of patients continue antipsychotics after discharge without clear indication—avoid inadvertent chronic use 3

Alternative Second-Line Option

• Trazodone: Start 25 mg/day, maximum 200-400 mg/day in divided doses (use caution with premature ventricular contractions due to orthostatic hypotension risk) 3

What NOT to Use

• Avoid benzodiazepines as first-line treatment (except for alcohol/benzodiazepine withdrawal) due to increased delirium incidence and duration, paradoxical agitation in ~10% of elderly patients, tolerance, addiction, and cognitive impairment 3
• Avoid typical antipsychotics (haloperidol, fluphenazine, thiothixene) as first-line due to 50% risk of tardive dyskinesia after 2 years of continuous use 3
• Do not newly prescribe cholinesterase inhibitors to prevent or treat agitation, as they are associated with increased mortality 3

Common Pitfalls to Avoid

• Never skip non-pharmacological interventions unless in an emergency with imminent harm 1, 2, 3
• Do not use antipsychotics for mild agitation—reserve only for severe, dangerous symptoms 3
• Do not continue antipsychotics indefinitely—review need at every visit and taper if no longer indicated 3
• Do not forget to treat pain—it is a major contributor to agitation in patients who cannot verbally communicate discomfort 1, 3