What is the most appropriate and safe medication adjustment for a 71-year-old woman with severe dementia, exit seeking, severe delusions and agitation, who is currently taking sertraline 100 mg daily, melatonin 10 mg twice daily, and trazodone 25 mg at bedtime?

Medication Adjustment for Severe Exit-Seeking, Delusions, and Agitation in Dementia

Increase trazodone to 50-100 mg at bedtime as the first medication adjustment, as this targets her exit-seeking behavior and agitation with a safer profile than antipsychotics in this 71-year-old severely demented patient. 1

Critical First Step: Rule Out Reversible Medical Causes

Before any medication adjustment, you must systematically investigate and treat:

• Pain assessment – a major driver of behavioral disturbances in patients who cannot verbally communicate discomfort 1
• Urinary tract infection or pneumonia – disproportionately common triggers of agitation in dementia 1
• Constipation and urinary retention – both significantly contribute to exit-seeking and restlessness 1
• Metabolic disturbances – dehydration, electrolyte abnormalities, hypoxia 1
• Medication review – identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion and agitation 1

Recommended Medication Adjustment Algorithm

Step 1: Optimize Trazodone (Preferred First-Line Adjustment)

Increase trazodone from 25 mg to 50-100 mg at bedtime, with a maximum dose of 200-400 mg/day in divided doses if needed. 1

Rationale:

• Trazodone specifically targets repetitive behaviors, verbal aggression, and oppositional behaviors (which includes exit-seeking) more effectively than other agents 2
• Comparable efficacy to haloperidol for overall agitation but with significantly fewer adverse effects 2
• Safer cardiovascular profile than antipsychotics – use caution only if she has premature ventricular contractions 1
• The current 25 mg dose is subtherapeutic; therapeutic range begins at 50 mg 1, 2

Monitoring: Assess response within 4 weeks using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q). 1

Step 2: If Trazodone Optimization Fails After 4 Weeks

Optimize sertraline from 100 mg to 150-200 mg daily (maximum 200 mg/day). 1

Rationale:

• SSRIs are first-line pharmacological treatment for chronic agitation in dementia 1
• Current 100 mg dose may be suboptimal; therapeutic range extends to 200 mg/day 1
• SSRIs significantly reduce overall neuropsychiatric symptoms, agitation, and depression in vascular cognitive impairment and dementia 1
• Well-tolerated with less effect on metabolism of other medications 1

Step 3: Only If Both Fail AND Severe Danger Persists

Add low-dose risperidone 0.25 mg at bedtime, titrating to 0.5-1 mg daily maximum. 1

Critical prerequisites before antipsychotic initiation:

• Patient must be severely agitated, threatening substantial harm to self or others 1
• Behavioral interventions documented as failed or impossible 1
• Mandatory discussion with surrogate decision maker about 1.6-1.7 times increased mortality risk, cardiovascular effects, cerebrovascular adverse reactions, falls, and stroke risk 1

Why risperidone over other antipsychotics:

• Preferred first-line antipsychotic for severe agitation with psychotic features 1
• More extensive evidence base than quetiapine for exit-seeking behaviors 1
• Lower risk of extrapyramidal symptoms at doses ≤2 mg/day 1

Monitoring requirements:

• Daily in-person examination to assess ongoing need 1
• Monitor for extrapyramidal symptoms, falls, sedation, metabolic changes, QT prolongation 1
• Attempt taper within 3-6 months to determine lowest effective maintenance dose 1

What NOT to Do

Do not add benzodiazepines – they increase delirium incidence and duration, cause paradoxical agitation in 10% of elderly patients, and worsen cognitive function. 1

Do not use haloperidol as first-line – reserve only for acute dangerous agitation requiring immediate intervention; typical antipsychotics carry 50% risk of tardive dyskinesia after 2 years in elderly patients. 1

Do not add multiple psychotropics simultaneously without first optimizing existing medications and treating reversible causes. 1

Non-Pharmacological Interventions (Implement Concurrently)

• Environmental modifications: Ensure adequate lighting, reduce excessive noise, install safety equipment (grab bars, door locks) 1
• Communication strategies: Use calm tones, simple one-step commands, gentle touch for reassurance 1
• Structured routines: Predictable daily schedule for meals, activities, bedtime 1
• Caregiver education: Behaviors are symptoms of dementia, not intentional actions 1
• ABC charting: Document antecedents, behaviors, and consequences to identify specific triggers of exit-seeking 1

Common Pitfalls to Avoid

• Starting antipsychotics before optimizing trazodone and sertraline – antipsychotics carry significantly higher mortality risk 1
• Ignoring reversible medical causes – pain, infection, and constipation are frequently overlooked drivers of exit-seeking 1
• Continuing antipsychotics indefinitely – approximately 47% of patients continue receiving antipsychotics without clear indication; review need at every visit 1
• Using doses of trazodone <50 mg – subtherapeutic and unlikely to provide benefit 2, 3