What should be done with olanzapine (olanzapine) 2.5 mg orally (PO) every night at bedtime (QHS) in an 81-year-old female patient with hepatic encephalopathy and elevated ammonia levels?

Discontinue Olanzapine in an Elderly Patient with Hepatic Encephalopathy

Olanzapine should be discontinued immediately in this 81-year-old female patient with alcoholic liver cirrhosis and hepatic encephalopathy due to the significant risk of worsening encephalopathy and potential hepatotoxicity. 1, 2

Rationale for Discontinuation

Hepatic Metabolism Concerns

• Olanzapine is highly metabolized by the liver with only 7% excreted unchanged in urine 2
• Primary metabolism occurs through CYP1A2 and CYP2D6 enzymes, which may be impaired in cirrhosis 2
• Patients with liver cirrhosis have reduced drug clearance, leading to increased drug exposure and potential toxicity

Age-Related Factors

• Elderly patients (≥65 years) have approximately 1.5 times longer elimination half-life of olanzapine compared to younger adults 2
• This patient's advanced age (81 years) compounds the risk of drug accumulation and adverse effects

Risk of Worsening Encephalopathy

• Antipsychotics can worsen hepatic encephalopathy by:
  • Further sedating the patient
  • Potentially interfering with ammonia metabolism
  • Adding to the cognitive burden in an already compromised brain

Management Algorithm

1. Immediate Action:

   • Discontinue olanzapine 2.5 mg PO QHS
   • Do not taper as the risk of continued exposure outweighs withdrawal concerns in this context

2. Address Underlying Hepatic Encephalopathy:

   • Ensure adequate lactulose therapy (first-line treatment) 1, 3
   • Initial dose: 25-30 mL lactulose every 1-2 hours until at least two soft bowel movements per day
   • Maintenance: 30-45 mL orally every 6-8 hours, titrated to maintain 2-3 soft bowel movements daily

3. Consider Adding Rifaximin:

   • If patient has had recurrent episodes of hepatic encephalopathy
   • Rifaximin 550 mg twice daily as an add-on to lactulose 1, 3
   • Note: Rifaximin should not be used alone without lactulose 1, 3

4. Psychiatric Symptom Management:

   • For agitation or psychosis that requires medication after olanzapine discontinuation:
     • Consider very low-dose haloperidol (0.5-1 mg) only for severe symptoms that pose safety risks
     • Use for shortest duration possible with close monitoring
     • Avoid benzodiazepines which can worsen encephalopathy 1

5. Monitor:

   • Mental status daily
   • Serum ammonia levels (though not proportional to HE severity, can help track trends) 1
   • Liver function tests
   • Electrolytes, particularly sodium and potassium

Important Considerations

Precipitating Factors

• Identify and address all potential precipitating factors for hepatic encephalopathy 1:
  • Medication non-compliance (particularly lactulose)
  • Infection
  • Gastrointestinal bleeding
  • Electrolyte disturbances
  • Constipation
  • Dehydration

Pitfalls to Avoid

• Do not substitute with other antipsychotics without careful consideration of hepatic metabolism
• Avoid benzodiazepines which can worsen encephalopathy 1
• Do not assume normal ammonia levels rule out hepatic encephalopathy - clinical presentation is more important than laboratory values 1
• Avoid overuse of lactulose which can lead to dehydration, hypernatremia, and aspiration risk 1, 3

Alternative Approaches for Psychiatric Symptoms

• Non-pharmacological interventions for agitation/confusion:
  • Reorientation strategies
  • Familiar caregivers when possible
  • Maintaining day-night cycle
  • Minimizing unnecessary stimulation

If psychiatric symptoms persist after hepatic encephalopathy resolves, psychiatric consultation should be obtained to evaluate for the safest possible management approach that prioritizes liver function.