What are the recommended nonsedating medications for an adult or geriatric patient with a history of psychiatric disorders or dementia presenting with aggression?

Nonsedating Medications for Aggression in Adults and Geriatric Patients

First-Line Pharmacological Treatment: SSRIs

For chronic aggression in dementia or psychiatric disorders, SSRIs are the preferred nonsedating first-line pharmacological option, with citalopram 10-40 mg/day or sertraline 25-200 mg/day recommended after behavioral interventions have been attempted. 1

SSRI Dosing and Monitoring

• Citalopram: Start at 10 mg/day, maximum 40 mg/day 1
• Sertraline: Start at 25-50 mg/day, maximum 200 mg/day 1
• Assess response after 4 weeks of adequate dosing using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) 1
• If no clinically significant response after 4 weeks, taper and withdraw 1
• SSRIs significantly reduce overall neuropsychiatric symptoms, agitation, and depression in patients with vascular cognitive impairment and dementia 1
• Sertraline has less effect on metabolism of other medications, making it particularly suitable for patients on multiple medications 1

Why SSRIs Are Nonsedating First-Line

• SSRIs provide therapeutic benefit without the sedation, falls risk, and mortality concerns associated with antipsychotics 1
• They require 4-8 weeks for full therapeutic effect, making them appropriate for chronic rather than acute aggression 1
• Well-tolerated with minimal anticholinergic effects that could worsen cognition 1

Second-Line Nonsedating Option: Trazodone

Trazodone 25-400 mg/day in divided doses is a second-line nonsedating alternative when SSRIs have failed or are not tolerated. 1

Trazodone Specifics

• Start at 25 mg/day, titrate gradually 1
• Maximum dose 200-400 mg/day in divided doses 1
• Use caution in patients with premature ventricular contractions due to orthostatic hypotension risk 1
• Falls risk of approximately 30% in real-world studies 1
• Takes 2-4 weeks to become effective, useful only for mild to moderate agitation 1

Critical Algorithm: When Medications Are Appropriate

Step 1: Mandatory Non-Pharmacological Interventions First

Medications should ONLY be used after systematic attempts at behavioral interventions, with three exceptions: major depression with suicidal ideation, psychosis causing harm, or aggression causing imminent risk to self or others. 2

• Identify and treat pain (major contributor to behavioral disturbances) 1
• Rule out urinary tract infections, pneumonia, constipation, urinary retention, dehydration 1
• Review all medications for anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen agitation 1
• Implement environmental modifications: adequate lighting, reduced noise, structured routines 1
• Use calm tones, simple one-step commands, gentle touch for reassurance 1

Step 2: SSRI Initiation for Chronic Aggression

• Begin citalopram 10 mg/day or sertraline 25-50 mg/day 1
• Document baseline severity using quantitative measures 1
• Titrate to minimum effective dose over 4-8 weeks 1

Step 3: Reassessment at 4 Weeks

• If clinically significant response: continue at lowest effective dose 1
• If no response: taper and withdraw, consider trazodone as alternative 1
• Periodically reassess need for continued medication even with positive response 1

What NOT to Use for Nonsedating Aggression Management

Avoid These Sedating Options

• Benzodiazepines: Cause tolerance, addiction, cognitive impairment, and paradoxical agitation in 10% of elderly patients 1
• Typical antipsychotics (haloperidol): 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 1
• Quetiapine: More sedating with risk of transient orthostasis 1
• Olanzapine: Less effective in patients over 75 years, carries sedation risk 1

Antipsychotics Are NOT Nonsedating Options

• Risperidone, olanzapine, quetiapine, and haloperidol all carry significant sedation risk 1
• Reserved ONLY for severe, dangerous agitation with psychotic features after SSRI failure 1
• Associated with 1.6-1.7 times higher mortality risk than placebo in elderly dementia patients 1
• Increase risk of falls, stroke, QT prolongation, and metabolic changes 1

Special Populations and Considerations

Vascular Dementia

• SSRIs are explicitly designated as first-line pharmacological treatment for agitation in vascular dementia 1
• Antipsychotics carry three-fold increased stroke risk in elderly patients with dementia, making them particularly unsuitable for vascular disease 1

Lewy Body Dementia

• Quetiapine 12.5 mg twice daily is first-line if antipsychotic needed (though sedating) 3
• Avoid typical antipsychotics due to severe sensitivity reactions 3
• SSRIs remain preferred nonsedating option for chronic agitation 1

Parkinson's Disease with Aggression

• Quetiapine is first-line antipsychotic if needed, but SSRIs should be attempted first for nonsedating management 1, 4

Common Pitfalls to Avoid

• Never continue antipsychotics indefinitely: Review need at every visit, taper within 3-6 months 1
• Don't use antipsychotics for mild agitation: They are unlikely to impact unfriendliness, poor self-care, repetitive questioning, or wandering 2
• Don't skip the 4-week SSRI trial: Inadequate duration is a common reason for perceived treatment failure 1
• Don't add medications without addressing reversible causes: Pain, infection, and constipation must be treated first 1
• Don't use buspirone for BPSD: Limited evidence and contributes to polypharmacy without clear benefit 1

Duration of Treatment

• SSRIs for chronic agitation: Continue for 9 months after first episode, then reassess 1
• Trazodone: Reassess need after 3-6 months 1
• Any psychotropic: Attempt taper within 3-6 months to determine lowest effective maintenance dose 1
• Approximately 47% of patients continue receiving medications after discharge without clear indication—avoid inadvertent chronic use 1