In a 66-year-old woman with dementia who is anxious and pacing despite quetiapine 25 mg twice daily, what additional medication can be given to help?

Management of Anxiety and Pacing in a 66-Year-Old Woman with Dementia on Quetiapine

Add an SSRI—specifically citalopram 10 mg daily or sertraline 25–50 mg daily—as first-line pharmacological treatment for chronic agitation and anxiety in dementia, and systematically investigate reversible medical causes (pain, infection, constipation, urinary retention) before any medication adjustment. 1

Critical First Step: Rule Out Reversible Medical Causes

Before adding any medication, you must systematically investigate and treat underlying medical triggers that commonly drive behavioral symptoms in dementia patients who cannot verbally communicate discomfort:

• Pain assessment and management is a major contributor to behavioral disturbances and must be addressed first 1
• Check for urinary tract infections and pneumonia, which are disproportionately common triggers of agitation in dementia 1
• Evaluate for constipation and urinary retention, both of which significantly contribute to restlessness and pacing 1
• Review all medications to identify and discontinue anticholinergic agents (diphenhydramine, hydroxyzine, oxybutynin, cyclobenzaprine) that worsen confusion and agitation 1
• Assess for metabolic disturbances including dehydration, electrolyte abnormalities, and hypoxia 1

Non-Pharmacological Interventions Must Be Intensified

The American Geriatrics Society and American Psychiatric Association require documented implementation of behavioral approaches before adding medications 1:

• Use calm tones, simple one-step commands, and gentle touch for reassurance rather than complex multi-step instructions 1
• Ensure adequate lighting and reduce excessive noise to minimize overstimulation 1
• Establish predictable daily routines with structured activities, including at least 30 minutes of sunlight exposure daily 1
• Allow adequate time for the patient to process information before expecting a response 1
• Use ABC (antecedent-behavior-consequence) charting to identify specific triggers of the pacing behavior 1

Pharmacological Treatment: Add an SSRI as First-Line

SSRIs are the preferred first-line pharmacological option for chronic agitation and anxiety in dementia, with substantially better safety profiles than increasing or adding additional antipsychotics 1:

Recommended SSRI Options:

• Citalopram: Start 10 mg daily, maximum 40 mg daily 1

  • Well-tolerated, though some patients experience nausea and sleep disturbances 1
  • Requires 4 weeks at adequate dosing to assess response 1

• Sertraline: Start 25–50 mg daily, maximum 200 mg daily 1

  • Well-tolerated with less effect on metabolism of other medications 1
  • Significantly reduces overall neuropsychiatric symptoms, agitation, and depression in vascular cognitive impairment and dementia 1

Why SSRIs Over Increasing Quetiapine:

The World Health Organization explicitly states that antipsychotics should not be used as first-line management for behavioral symptoms in dementia 1. Your patient is already on quetiapine 25 mg BID (50 mg total daily), which is within the therapeutic range for agitation (typical dosing 50–150 mg/day) 2. Increasing quetiapine further carries significant risks:

• Increased mortality risk (1.6–1.7 times higher than placebo) in elderly dementia patients 1, 3
• Recent 2025 data shows low-dose quetiapine for behavioral symptoms in older adults is associated with significantly higher rates of mortality (HR 3.1), dementia progression (HR 8.1), and falls (HR 2.8) compared to alternatives like trazodone 4
• Patients over 75 years respond less well to antipsychotics, particularly olanzapine, and short-term treatment is associated with increased mortality 1
• Risk of QT prolongation, dysrhythmias, sudden death, hypotension, pneumonia, falls, and metabolic effects 1

Alternative Second-Line Option: Trazodone

If SSRIs fail or are not tolerated after 4 weeks at adequate dosing, consider trazodone 25 mg daily (maximum 200–400 mg/day in divided doses) 1:

• Safer alternative to increasing antipsychotics with better tolerability profile 1
• Use caution in patients with premature ventricular contractions due to risk of orthostatic hypotension 1
• Falls risk of 30% in real-world studies, so monitor closely 1

What NOT to Do

Avoid Benzodiazepines:

• The American Geriatrics Society explicitly recommends avoiding benzodiazepines for routine agitation management in dementia (except for alcohol/benzodiazepine withdrawal) 1
• They increase delirium incidence and duration, cause paradoxical agitation in approximately 10% of elderly patients, and risk tolerance, addiction, cognitive impairment, and respiratory depression 1

Do Not Add Typical Antipsychotics:

• The American Academy of Family Physicians recommends avoiding typical antipsychotics (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 Anticholinergic Medications:

• Diphenhydramine, oxybutynin, and cyclobenzaprine worsen agitation and cognitive function in dementia 1

Monitoring and Reassessment Protocol

Once you initiate an SSRI:

• Evaluate 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 the medication 1
• Even with positive response, periodically reassess the need for continued medication 1
• Monitor for side effects including nausea, sleep disturbances, and falls 1

Critical Safety Discussion Required

Before initiating any new psychotropic medication, the American Psychiatric Association requires discussing with the patient (if feasible) and surrogate decision maker 1, 3:

• Increased mortality risk (1.6–1.7 times higher than placebo with antipsychotics) 1
• Cardiovascular effects and cerebrovascular adverse reactions 3
• Expected benefits and treatment goals 1
• Alternative non-pharmacological approaches 1
• Plans for ongoing monitoring and reassessment 1

Duration of Treatment

If the SSRI provides benefit, continue treatment but attempt taper within 9 months to reassess necessity 1. For the existing quetiapine, the American Geriatrics Society recommends attempting taper within 3–6 months to determine the lowest effective maintenance dose, as approximately 47% of patients continue receiving antipsychotics after discharge without clear indication 1.

Common Pitfalls to Avoid

• Do not add multiple psychotropics simultaneously without first treating reversible medical causes 1
• Do not continue antipsychotics indefinitely—review need at every visit and taper if no longer indicated 1
• Do not use antipsychotics for mild agitation or behaviors like unfriendliness, poor self-care, repetitive questioning, or wandering, as these are unlikely to respond to psychotropics 1
• Do not ignore environmental modifications—these have substantial evidence for efficacy without mortality risks 1