What antipsychotics (anti-psychotic medications) should be used in patients with schizophrenia, bipolar disorder, or dementia, particularly in geriatric patients?

Antipsychotic Selection by Clinical Context

Dementia with Agitation or Psychosis (Geriatric Patients)

For elderly patients with dementia-related behavioral symptoms, antipsychotics should be reserved exclusively for severe, dangerous agitation after non-pharmacological interventions have failed, using risperidone 0.25-1.25 mg/day as first-line, with quetiapine 12.5-150 mg/day as the preferred alternative. 1, 2

Treatment Algorithm for Dementia-Related Agitation:

Step 1: Mandatory Non-Pharmacological Interventions First

• Systematically investigate and treat reversible medical causes: pain (major contributor), urinary tract infections, pneumonia, constipation, urinary retention, dehydration, and medication side effects (especially anticholinergics) 2
• Implement environmental modifications: adequate lighting, reduced noise, structured routines, calm communication with simple one-step commands 1, 2
• These interventions must be attempted and documented as failed before any medication is considered 1, 2

Step 2: Determine if Medication is Warranted

• Antipsychotics are appropriate ONLY when: patient is severely agitated, threatening substantial harm to self or others, symptoms are dangerous or cause significant distress, and behavioral interventions have been thoroughly attempted 1, 2
• Do NOT use antipsychotics for: mild agitation, unfriendliness, poor self-care, memory problems, repetitive questioning, rejection of care, shadowing, or wandering 2

Step 3: Medication Selection for Dementia

For chronic agitation WITHOUT psychotic features:

• First-line: SSRIs - Citalopram 10 mg/day (max 40 mg/day) or Sertraline 25-50 mg/day (max 200 mg/day) 2
• Assess response at 4 weeks; taper and discontinue if no benefit 1, 2

For severe agitation WITH psychotic features or aggression:

• First-line: Risperidone 0.25 mg at bedtime, titrate to 0.5-1.25 mg/day (max 2-3 mg/day; extrapyramidal symptoms increase at >2 mg/day) 2, 3
• Second-line: Quetiapine 12.5 mg twice daily, titrate to 50-150 mg/day (max 200 mg twice daily; more sedating, risk of orthostatic hypotension) 2, 3
• Third-line: Olanzapine 2.5 mg at bedtime (max 10 mg/day; less effective in patients >75 years) 1, 2, 3

Step 4: Critical Safety Discussion Required

• Before initiating ANY antipsychotic, discuss with patient (if feasible) and surrogate decision maker: 1.6-1.7 times increased mortality risk, cardiovascular effects including QT prolongation and sudden death, cerebrovascular events (stroke/TIA), falls, pneumonia, and metabolic changes 1, 2, 4
• The absolute mortality risk increase ranges from 2.0% for quetiapine (NNH=50) to 3.8% for haloperidol (NNH=26) over 180 days 4

Step 5: Dosing and Monitoring

• Start at lowest effective dose and titrate slowly 1, 2
• Evaluate response daily with in-person examination initially, then at 4 weeks using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) 1, 2
• If no clinically significant response after 4 weeks at adequate dose, taper and withdraw 1, 2
• Monitor for: extrapyramidal symptoms, falls, sedation, metabolic changes, QT prolongation, cognitive worsening 2

Step 6: Duration and Discontinuation

• Target duration: taper within 3-6 months to determine lowest effective maintenance dose 3
• Approximately 47% of patients continue antipsychotics after discharge without clear indication—avoid inadvertent chronic use 2
• Periodically reassess need at every visit; taper if no longer indicated 2

What NOT to Use in Dementia:

• Avoid typical antipsychotics (haloperidol, fluphenazine, thiothixene) as first-line due to 50% risk of tardive dyskinesia after 2 years of continuous use 2
• Avoid benzodiazepines for routine agitation management—they increase delirium incidence/duration, cause paradoxical agitation in 10% of elderly patients, and risk respiratory depression 1, 2
• Avoid anticholinergic medications (diphenhydramine, oxybutynin)—they worsen agitation and cognitive function 2

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Acute Severe Agitation in Geriatric Patients (Emergency Situations)

For acute severe agitation with imminent risk of harm when behavioral interventions have failed, use haloperidol 0.5-1 mg orally or subcutaneously (maximum 5 mg daily in elderly), reserving this only for the shortest duration possible with daily reassessment. 2

Acute Management Protocol:

First: Address Reversible Causes

• Check for and treat: hypoxia, urinary retention, constipation, pain, infections (especially UTI and pneumonia), metabolic disturbances 2

Medication for Acute Agitation:

• Haloperidol 0.5-1 mg orally, IM, or subcutaneously every 2 hours as needed (max 5 mg daily in elderly) 2
• Monitor ECG for QTc prolongation and watch for extrapyramidal symptoms 2
• Use lowest dose for shortest duration; evaluate need daily 1, 2

Alternative if haloperidol contraindicated:

• Olanzapine 2.5 mg IM (reduced from standard 5 mg dose due to elderly status; risk of oversedation and respiratory depression) 2

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Schizophrenia in Older Adults

For late-life schizophrenia, risperidone 1.25-3.5 mg/day is first-line, with quetiapine 100-300 mg/day, olanzapine 7.5-15 mg/day, and aripiprazole 15-30 mg/day as high second-line alternatives. 3

• Continue treatment indefinitely at the lowest effective dose 3
• Regular monitoring for metabolic effects, extrapyramidal symptoms, and cardiovascular risks is essential 2

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Bipolar Disorder in Older Adults

For geriatric mania with psychosis, combine a mood stabilizer with risperidone 1.25-3.0 mg/day or olanzapine 5-15 mg/day as first-line treatment, with quetiapine 50-250 mg/day as high second-line. 3

Bipolar Treatment Algorithm:

Mild nonpsychotic mania:

• Mood stabilizer alone (first-line); discontinue any antidepressant 3

Severe nonpsychotic mania:

• Mood stabilizer alone OR mood stabilizer + antipsychotic (both first-line); discontinue any antidepressant 3

Psychotic mania:

• Mood stabilizer + antipsychotic (98% first-line recommendation) 3
• Duration: continue antipsychotic for 3 months after stabilization, then reassess 3

Bipolar depression:

• Antipsychotic + antidepressant (98% first-line for psychotic depression) 3
• Continue antipsychotic for 6 months after remission 3

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Special Populations and Comorbidities

Parkinson's Disease with Psychosis:

• First-line: Quetiapine (very low doses, 12.5 mg twice daily, titrate slowly) 1, 5, 3
• Alternatives: Clozapine or pimavanserin 1
• Absolutely avoid: Typical antipsychotics (haloperidol), risperidone, olanzapine due to severe sensitivity reactions and high risk of extrapyramidal symptoms 5, 3

Lewy Body Dementia with Psychosis:

• Quetiapine 12.5 mg twice daily (max 200 mg twice daily) with slow titration 5
• Monitor closely for worsening cognition, extrapyramidal symptoms, orthostatic hypotension 5
• Avoid typical antipsychotics entirely 5

Diabetes, Dyslipidemia, or Obesity:

• Avoid: Clozapine, olanzapine, conventional antipsychotics (especially low- and mid-potency) 3
• Prefer: Risperidone or quetiapine 3

QTc Prolongation or Congestive Heart Failure:

• Avoid: Clozapine, ziprasidone, conventional antipsychotics (especially low- and mid-potency) 3
• Prefer: Risperidone or quetiapine with ECG monitoring 2, 3

Cognitive Impairment, Constipation, or Anticholinergic Sensitivity:

• Prefer: Risperidone, with quetiapine as high second-line 3
• Avoid medications with high anticholinergic burden 2

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Critical Pitfalls to Avoid

Common Errors:

• Using antipsychotics for mild behavioral symptoms without attempting non-pharmacological interventions 1, 2
• Continuing antipsychotics indefinitely without regular reassessment (47% continue without indication) 2
• Using benzodiazepines as first-line for agitated delirium in elderly patients 1, 2
• Prescribing typical antipsychotics as first-line in dementia (50% tardive dyskinesia risk after 2 years) 2
• Failing to discuss mortality risks with patients/surrogates before initiating treatment 1, 2
• Using standard adult doses without dose reduction for elderly patients 2
• Prescribing olanzapine to patients >75 years (significantly less effective in this age group) 1, 2

Dose-Response Mortality Risk:

• Atypical antipsychotics show dose-dependent mortality increase—high doses have 3.5% greater mortality than low doses 4
• When compared directly, risperidone and olanzapine have higher dose-adjusted mortality risk than quetiapine 4

1, 2, 5, 3, 4