What is the appropriate starting dose of olanzapine (Zyprexa) for an 89‑year‑old man with acute delirium?

Starting Dose of Olanzapine (Zyprexa) for an 89-Year-Old Male with Acute Delirium

Start with olanzapine 2.5 mg orally once daily at bedtime, which is the recommended initial dose for elderly patients with delirium, particularly those over 75 years who respond less well to antipsychotics and require lower starting doses to minimize sedation, falls, and orthostatic hypotension. 1, 2

Critical Prerequisites Before Initiating Any Antipsychotic

Before administering olanzapine, you must systematically investigate and treat reversible medical causes that commonly drive delirium in elderly patients who cannot verbally communicate discomfort 1:

• Pain assessment and management – untreated pain is a major contributor to behavioral disturbances 1
• Infections – check for urinary tract infections and pneumonia, which are disproportionately common triggers 1
• Metabolic disturbances – evaluate for hypoxia, dehydration, electrolyte abnormalities, and hyperglycemia 3, 1
• Constipation and urinary retention – both significantly contribute to restlessness and agitation 1
• Medication review – identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion 1

Specific Dosing Algorithm for This 89-Year-Old Patient

Initial dose: Olanzapine 2.5 mg orally once daily at bedtime 1, 2

This lower starting dose is critical because 1, 4:

• Patients over 75 years respond less well to antipsychotics, particularly olanzapine
• Elderly patients are more susceptible to sedation, falls, and orthostatic hypotension
• Starting at 2.5 mg minimizes these risks while providing therapeutic benefit

Dose titration (if needed after 24-48 hours):

• If delirium persists and the patient tolerates the initial dose, increase to 5 mg once daily at bedtime 2, 4
• Maximum dose in elderly patients: 10 mg/day – do not exceed this without compelling justification 1, 2
• Dose adjustments should occur at intervals of not less than 1 week after initial titration, as steady-state concentrations require approximately one week to achieve 2

Why Olanzapine Over Haloperidol in This Case

While haloperidol 0.5-1 mg is the traditional first-line medication for acute delirium in elderly patients 3, 1, olanzapine offers specific advantages 5, 6:

• Lower risk of extrapyramidal symptoms – particularly important in frail elderly patients 2, 5
• Less akathisia – which can be mistaken for worsening delirium 7, 5
• Effective for delirium – studies show 45-50% of patients achieve significant improvement on the Delirium Rating Scale 6
• Better tolerability – no injection site reactions with subcutaneous administration if oral route becomes unavailable 8

However, haloperidol remains preferred if 1:

• The patient has severe, dangerous agitation requiring immediate control
• There is concern about metabolic effects (olanzapine carries higher risk of weight gain, diabetes, dyslipidemia) 2
• The patient has Parkinson's disease or Lewy body dementia (quetiapine would be first-line instead) 4

Critical Safety Discussion Required Before Initiation

You must discuss with the patient's surrogate decision maker 1:

• Increased mortality risk – 1.6-1.7 times higher than placebo in elderly dementia patients
• Cardiovascular effects – QT prolongation, sudden death, hypotension
• Cerebrovascular adverse events – particularly stroke risk
• Falls risk – due to sedation and orthostatic hypotension
• Expected benefits and treatment goals – symptom control, not cure

Administration and Monitoring

Route of administration:

• Oral (preferred): 2.5 mg tablet or orally disintegrating tablet (ODT) at bedtime 2
• Subcutaneous (if oral not feasible): 2.5-5 mg SC every 8 hours – well tolerated with no injection site toxicity in studies 8
• Intramuscular (emergency only): 2.5 mg IM, reduced from the standard 5-10 mg adult dose 2

Daily monitoring requirements 1, 2:

• In-person examination to evaluate ongoing need
• Orthostatic vital signs (blood pressure sitting and standing)
• Assessment for extrapyramidal symptoms (tremor, rigidity, bradykinesia)
• Falls risk assessment
• Sedation level and cognitive status
• ECG monitoring if patient has known cardiac arrhythmias or is on other QTc-prolonging medications 2

Duration of Treatment

For acute delirium: Attempt to taper and discontinue within 1 week after delirium resolves 4

The goal is to use the lowest effective dose for the shortest possible duration 1. Once the underlying cause of delirium is treated and symptoms improve:

• Begin tapering within 3-7 days of symptom resolution 4
• Reassess daily whether continued treatment is necessary 1
• Avoid inadvertent chronic use – approximately 47% of patients continue receiving antipsychotics after discharge without clear indication 1

What NOT to Do

Avoid these common pitfalls 1, 2:

• Do not combine with benzodiazepines – fatalities have been reported with concurrent use of high-dose olanzapine and benzodiazepines due to oversedation and respiratory depression 2
• Do not use benzodiazepines as first-line for delirium (except alcohol/benzodiazepine withdrawal) – they increase delirium incidence and duration, cause paradoxical agitation in ~10% of elderly patients 1
• Do not start at doses higher than 2.5 mg in this 89-year-old patient – higher initial doses provide no evidence of greater effectiveness and result in significantly greater risk of sedation and side effects 1
• Do not exceed 10 mg/day in elderly patients – the risk-benefit ratio becomes unfavorable 2, 4
• Do not continue indefinitely – review need at every visit and taper as soon as clinically appropriate 1

Alternative if Olanzapine is Contraindicated or Ineffective

If olanzapine is not appropriate or fails after 24-48 hours at adequate dosing 3, 1:

Second-line: Haloperidol 0.5-1 mg orally or subcutaneously (maximum 5 mg/day in elderly) 3, 1

• More extensive evidence base for acute delirium
• Lower risk of metabolic effects
• Higher risk of extrapyramidal symptoms

Third-line: Quetiapine 12.5-25 mg twice daily (if Parkinson's disease or Lewy body dementia) 4

• First-line for patients with movement disorders
• More sedating, higher risk of orthostatic hypotension