What medication can be added to treat clinically significant agitation in an older adult with dementia?

Medication for Dementia-Related Agitation

For clinically significant agitation in dementia, SSRIs (citalopram or sertraline) are the first-line pharmacological treatment after non-pharmacological interventions have been attempted, with antipsychotics reserved only for severe, dangerous agitation that poses imminent risk of harm. 1

Prerequisites Before Any Medication

Before prescribing any psychotropic medication, you must systematically investigate and treat reversible medical causes that commonly drive agitation in dementia patients who cannot verbally communicate discomfort 1:

• Pain assessment and management – a major contributor to behavioral disturbances 1
• Infections – check for urinary tract infections and pneumonia 1
• Metabolic disturbances – evaluate for hypoxia, dehydration, electrolyte abnormalities, hyperglycemia 1
• Constipation and urinary retention – both significantly contribute to restlessness 1
• Medication review – identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion and agitation 1

Non-Pharmacological Interventions (Mandatory First-Line)

Behavioral interventions must be attempted and documented as failed before considering medications, unless there is an emergency situation with imminent risk of harm 1:

• Environmental modifications – ensure adequate lighting (especially late afternoon), reduce excessive noise, provide predictable daily routines 1, 2
• Communication strategies – use calm tones, simple one-step commands, gentle touch for reassurance, allow adequate time for processing 1
• Bright light therapy – 2 hours of morning bright light at 3,000-5,000 lux decreases agitation 1
• Physical activity – at least 30 minutes of daily sunlight exposure and supervised mobility 1
• Caregiver education – teach that behaviors are symptoms of dementia, not intentional actions 1

First-Line Pharmacological Treatment: SSRIs

When non-pharmacological approaches are insufficient after adequate trial (typically 24-48 hours to several weeks depending on severity), initiate an SSRI as the preferred medication 1:

Citalopram

• Starting dose: 10 mg daily 1
• Maximum dose: 40 mg daily 1
• Well-tolerated, though some patients experience nausea and sleep disturbances 1

Sertraline

• Starting dose: 25-50 mg daily 1
• Maximum dose: 200 mg daily 1
• Top choice due to minimal drug interactions and excellent tolerability 1

Evidence Supporting SSRIs

• SSRIs significantly reduce overall neuropsychiatric symptoms, agitation, and depression in patients with vascular cognitive impairment and dementia 1
• The Canadian Stroke Best Practice Recommendations explicitly designate SSRIs as first-line pharmacological treatment for agitation in dementia 1
• SSRIs provide broader neuropsychiatric benefits with substantially lower cerebrovascular risk compared to antipsychotics 1

Monitoring SSRIs

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

Second-Line: Trazodone

If SSRIs fail or are not tolerated, consider trazodone 1:

• Starting dose: 25 mg daily 1
• Maximum dose: 200-400 mg daily in divided doses 1
• Use caution in patients with premature ventricular contractions due to orthostatic hypotension risk 1
• Preferred over benzodiazepines, which cause tolerance, addiction, cognitive impairment, and paradoxical agitation in 10% of elderly patients 1

Antipsychotics: Reserved for Severe, Dangerous Agitation Only

Antipsychotics should ONLY be used when 1:

1. The patient is severely agitated, distressed, or threatening substantial harm to self or others
2. Behavioral interventions have been thoroughly attempted and documented as insufficient
3. The patient has severe agitation with psychotic features (delusions, hallucinations)
4. There is an emergency situation with imminent risk of harm

Critical Safety Discussion Required

Before initiating any antipsychotic, you MUST discuss with the patient (if feasible) and surrogate decision maker 1:

• Increased mortality risk – 1.6-1.7 times higher than placebo 1
• Cardiovascular effects – QT prolongation, dysrhythmias, sudden death, hypotension 1
• Cerebrovascular adverse reactions – increased stroke risk 1
• Falls, pneumonia, metabolic changes 1

Risperidone (Preferred Antipsychotic)

• Starting dose: 0.25 mg once daily at bedtime 1, 3
• Target dose: 0.5-1.25 mg daily 1, 3
• Maximum dose: 2 mg daily 1, 3
• Extrapyramidal symptoms increase dramatically above 2 mg/day 1
• Moderate-certainty evidence shows it probably reduces agitation slightly (SMD -0.21) 3

Quetiapine (Alternative)

• Starting dose: 12.5 mg twice daily 1, 2
• Maximum dose: 200 mg twice daily 1, 2
• More sedating with risk of transient orthostasis 1, 2
• Monitor closely for sedation and orthostatic hypotension 2

Olanzapine

• Starting dose: 2.5 mg at bedtime 1
• Maximum dose: 10 mg daily 1
• Less effective in patients over 75 years 1

Haloperidol (Acute Severe Agitation Only)

• Use only for acute severe agitation with imminent risk of harm when rapid control is needed 1
• Dose: 0.5-1 mg orally or subcutaneously 1
• Maximum: 5 mg daily in elderly patients 1
• Higher doses provide no additional benefit and significantly increase adverse effects 1
• ECG monitoring required for QTc prolongation 1

Duration and Monitoring of Antipsychotics

• Use the lowest effective dose for the shortest possible duration 1
• Evaluate daily with in-person examination to assess ongoing need 1
• Attempt taper within 3-6 months to determine if still needed 1
• Monitor for: extrapyramidal symptoms, falls, sedation, metabolic changes, QT prolongation, cognitive worsening 1
• Approximately 47% of patients continue receiving antipsychotics after discharge without clear indication – avoid inadvertent chronic use 1

What NOT to Use

Avoid Benzodiazepines

Benzodiazepines should NOT be used for routine agitation management (except for alcohol or 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, falls 1

Avoid Typical Antipsychotics as First-Line

Avoid haloperidol, fluphenazine, thiothixene as first-line therapy due to 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 1

Avoid Cholinesterase Inhibitors for Agitation

Do not newly prescribe cholinesterase inhibitors to prevent or treat delirium or agitation – associated with increased mortality 1

Common Pitfalls to Avoid

• Do not add medications without first treating reversible medical causes (pain, infection, metabolic issues) 1
• Do not use antipsychotics for mild agitation or behaviors like unfriendliness, poor self-care, repetitive questioning, or wandering 1
• Do not continue antipsychotics indefinitely – review need at every visit and taper if no longer indicated 1
• Do not combine high-dose benzodiazepines with antipsychotics – risk of fatal respiratory depression 1
• Patients over 75 years respond less well to antipsychotics, particularly olanzapine 1