What adjustments should be made to the treatment plan of an elderly male patient with aggressive behaviors, who is taking citalopram, divalproex, trazodone, and quetiapine, and has a moderate gene-drug interaction for sertraline, trazodone, and olanzapine based on Genesite testing results?

Treatment Plan Adjustments for Elderly Male with Aggressive Behaviors

Critical Immediate Action: Address Polypharmacy and Genetic Testing Results

The genetic testing showing moderate gene-drug interactions for trazodone should prompt immediate consideration of discontinuing or replacing trazodone, as this PRN medication adds to polypharmacy without clear benefit and carries increased risk given the genetic interaction. 1

Step 1: Systematic Deprescribing Before Adding Medications

• Discontinue trazodone 100 mg PRN immediately due to the moderate gene-drug interaction identified on Genesite testing and lack of evidence supporting its use for aggressive behaviors in elderly patients 1
• Trazodone takes 2-4 weeks to become effective and is only useful for mild to moderate agitation, making PRN dosing inappropriate 1
• The current regimen represents problematic polypharmacy (4 psychotropic medications) that increases fall risk, cognitive impairment, and mortality without demonstrated additive benefit 1

Step 2: Optimize Existing SSRI Therapy First

Before making any other medication changes, increase citalopram from the subtherapeutic dose of 10 mg to a therapeutic dose of 20-40 mg daily, as SSRIs are first-line pharmacological treatment for chronic agitation in elderly patients with aggressive behaviors. 1

• Citalopram 10 mg is below the therapeutic range for behavioral symptoms in dementia 1
• The target dose should be 20-40 mg daily (maximum 40 mg/day in elderly patients due to QTc prolongation risk) 2
• Allow 4 weeks at adequate dosing (minimum 20 mg daily) before assessing response using quantitative measures such as the Cohen-Mansfield Agitation Inventory or NPI-Q 1
• Citalopram has minimal drug interactions and is well-tolerated, though some patients experience nausea and sleep disturbances 3

Step 3: Optimize Quetiapine Dosing

Increase quetiapine from 25 mg twice daily (50 mg total) to a therapeutic dose of 50-150 mg/day, as the current dose is subtherapeutic for managing aggressive behaviors in elderly patients. 4

• The current dose of 50 mg/day is below the recommended range of 50-150 mg/day for agitated dementia 4
• For elderly patients, start with 12.5 mg twice daily and titrate to 50-150 mg/day in divided doses 5
• Quetiapine is more sedating and carries risk of orthostatic hypotension, requiring blood pressure monitoring 1
• Use the lowest effective dose for the shortest duration, with daily evaluation and attempt to taper within 3-6 months 1

Step 4: Continue Divalproex with Monitoring

Maintain divalproex at current dose with therapeutic drug monitoring to ensure levels are in the therapeutic range (50-125 mcg/mL), as mood stabilizers have evidence for treating aggressive behavior in elderly patients. 6

• Divalproex sodium is recommended for severe agitation without psychotic features in elderly patients 1
• Monitor liver enzymes and coagulation parameters regularly 6
• Ensure therapeutic blood levels are achieved through TDM 6

Step 5: Investigate and Treat Reversible Medical Causes

Systematically evaluate for pain, urinary tract infections, constipation, dehydration, and medication side effects before attributing behaviors solely to psychiatric causes. 1

• Pain is a major contributor to behavioral disturbances in patients who cannot verbally communicate discomfort 1
• Check for urinary tract infections and pneumonia, which are disproportionately common contributors to neuropsychiatric symptoms 1
• Evaluate for constipation and urinary retention, which significantly contribute to restlessness and aggression 1
• Review all medications for anticholinergic properties that worsen confusion and agitation 1

Step 6: Implement Intensive Non-Pharmacological Interventions

Use calm tones, simple one-step commands, environmental modifications (adequate lighting, reduced noise), and structured daily routines as these have substantial evidence for efficacy without mortality risks. 1

• Ensure adequate lighting and reduce excessive noise to minimize overstimulation 1
• Provide predictable daily routines and structured activities 1
• Use ABC (antecedent-behavior-consequence) charting to identify specific triggers of aggressive behavior 1
• Allow adequate time for the patient to process information before expecting a response 1

Critical Safety Warnings and Monitoring

Mortality Risk Discussion Required

All antipsychotics increase mortality risk 1.6-1.7 times higher than placebo in elderly patients with dementia, and this must be discussed with the patient's surrogate decision maker before continuing or adjusting treatment. 1

• Discuss cardiovascular risks including QTc prolongation, sudden death, stroke risk, hypotension, and falls 1
• Document this discussion in the medical record 1

Monitoring Requirements

• ECG monitoring for QTc prolongation is necessary when using both citalopram (maximum 40 mg/day due to QTc risk) and quetiapine 2
• Daily in-person examination to evaluate ongoing need and assess for side effects 1
• Monitor for extrapyramidal symptoms, falls, sedation, metabolic changes, and cognitive worsening 1
• Evaluate response within 4 weeks using the same quantitative measure used at baseline 1

What NOT to Do

• Do not add benzodiazepines for routine agitation management, as they increase delirium incidence and duration, cause paradoxical agitation in approximately 10% of elderly patients, and worsen cognitive function 1
• Do not continue trazodone given the moderate gene-drug interaction and lack of evidence for aggressive behaviors 1
• Do not add additional antipsychotics without first optimizing the current regimen and attempting deprescribing 1
• Do not use typical antipsychotics (haloperidol, perphenazine) as they carry a 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 7

Reassessment Timeline

• Evaluate response to citalopram dose increase within 4 weeks using quantitative measures 1
• If no clinically significant response after 4 weeks at adequate dose (minimum 20 mg daily), consider tapering and withdrawing 1
• Attempt to taper quetiapine within 3-6 months to determine the lowest effective maintenance dose or if still needed 1
• Review need for all psychotropics at every visit, as approximately 47% of patients continue receiving antipsychotics after discharge without clear indication 1