What is the best approach to manage Behavioral and Psychological Symptoms of Dementia (BPSD) in an elderly patient with dementia who is experiencing agitation and side effects from Risperidone (risperidone)?

Management of BPSD Agitation When Risperidone Causes Side Effects

Immediate Action: Switch to Alternative Medication

If risperidone is causing intolerable side effects in an elderly patient with dementia and agitation, switch to quetiapine (starting at 12.5 mg twice daily, maximum 200 mg twice daily) or consider an SSRI (citalopram 10 mg/day or sertraline 25-50 mg/day) depending on symptom severity and the presence of psychotic features. 1, 2

Step 1: Identify and Document Specific Side Effects

Before switching medications, determine which adverse effects are occurring:

• Extrapyramidal symptoms (tremor, rigidity, bradykinesia, akathisia) - occur in up to 50% of patients, especially at doses >2 mg/day 1, 3, 4
• Cognitive decline - worsening confusion or memory 4
• Sedation or orthostatic hypotension 3
• Metabolic effects (weight gain, hyperglycemia) 3
• Falls or gait disturbance 1

The FDA label explicitly warns that risperidone causes parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, orthostatic hypotension, and cognitive impairment as common adverse reactions 3.

Step 2: Reassess Medical and Environmental Triggers

Before changing medications, aggressively investigate reversible causes that may be driving the agitation:

• Pain assessment - a major contributor to behavioral disturbances in patients who cannot verbally communicate discomfort 1
• Infections - urinary tract infections and pneumonia are common triggers 1
• Constipation and urinary retention 1
• Medication review - discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen agitation 1
• Environmental modifications - adequate lighting, reduced noise, structured routines 1, 5

Step 3: Select Alternative Pharmacological Treatment

For Agitation WITH Psychotic Features (delusions, hallucinations):

First-line alternative: Quetiapine 1, 2, 6

• Start at 12.5 mg twice daily (especially in frail elderly) 1, 2
• Titrate slowly to 50-150 mg/day 1, 6
• Maximum dose: 200 mg twice daily 1
• Advantages: Lower risk of extrapyramidal symptoms compared to risperidone, preferred in Parkinson's disease 2, 6
• Monitor for: Sedation and orthostatic hypotension (30% falls risk in real-world studies) 1, 2

Second-line alternative: Olanzapine 1, 6

• Start at 2.5 mg at bedtime 1
• Maximum dose: 10 mg/day 1
• Caution: Less effective in patients over 75 years, avoid in diabetes/dyslipidemia/obesity 1, 6

Third-line alternative: Brexiprazole 5

• Only after non-pharmacological interventions exhausted 5
• Requires structured monitoring with Cohen-Mansfield Agitation Inventory 5
• Discontinue if no response after 4 weeks 5

For Agitation WITHOUT Psychotic Features (chronic agitation, irritability):

First-line: SSRIs 1

• Citalopram: Start 10 mg/day, maximum 40 mg/day 1
• Sertraline: Start 25-50 mg/day, maximum 200 mg/day 1
• Rationale: Significantly reduce overall neuropsychiatric symptoms, agitation, and depression in vascular cognitive impairment and dementia 1
• Timeline: Assess response at 4 weeks; if no benefit, taper and discontinue 1

Second-line: Trazodone 1

• Start 25 mg/day, maximum 200-400 mg/day in divided doses 1
• Caution: Use caution in patients with premature ventricular contractions, risk of orthostatic hypotension 1

Third-line: Divalproex sodium 1

• For severe agitation without psychotic features 1
• Start 125 mg twice daily, titrate to therapeutic blood level 1
• Monitor liver enzymes and coagulation parameters 1

Step 4: Avoid These Medications

Never use as first-line alternatives:

• Typical antipsychotics (haloperidol, fluphenazine) - 50% risk of tardive dyskinesia after 2 years in elderly patients 1, 2
• Benzodiazepines - increase delirium incidence/duration, cause paradoxical agitation in 10% of elderly patients, risk of tolerance and addiction 1
• Anticholinergic agents - worsen confusion and agitation 1

Step 5: Critical Safety Discussion Required

Before initiating any alternative antipsychotic, discuss with the patient (if feasible) and surrogate decision-maker:

• Increased mortality risk - 1.6-1.7 times higher than placebo in elderly patients with dementia (FDA Black Box Warning) 1, 3
• Cerebrovascular adverse events including stroke 3
• Expected benefits and treatment goals 1
• Plans for ongoing monitoring and reassessment 1

Step 6: Monitoring Protocol After Medication Switch

• Evaluate response within 4 weeks using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) 1, 5
• Daily in-person examination to assess ongoing need and side effects 1
• Monitor for: Extrapyramidal symptoms, falls, sedation, metabolic changes, QT prolongation, cognitive worsening 1
• If no clinically significant response after 4 weeks at adequate dose: Taper and withdraw the medication 1, 5

Step 7: Duration of Treatment

• Agitated dementia: Taper within 3-6 months to determine lowest effective maintenance dose 6
• Review need at every visit and taper if no longer indicated 1
• Avoid inadvertent chronic use - approximately 47% of patients continue receiving antipsychotics after discharge without clear indication 1

Common Pitfalls to Avoid

• Do not continue antipsychotics indefinitely without regular reassessment 1
• Do not use antipsychotics for mild agitation - reserve for severe symptoms that are dangerous or cause significant distress 1
• Do not skip non-pharmacological interventions unless in an emergency situation 1, 5
• Do not use high doses - patients over 75 years respond less well to antipsychotics and require lower doses 1