What is the recommended restart dose for a patient with a history of taking Zyprexa (olanzapine) 5mg in the morning and 10mg at bedtime, who has not taken the medication in 3 months?

Restarting Olanzapine After 3-Month Discontinuation

For a patient who previously tolerated olanzapine 15 mg daily (5 mg AM + 10 mg HS) but has been off the medication for 3 months, restart at 2.5-5 mg once daily at bedtime, then titrate upward over 1-2 weeks to the previous therapeutic dose of 15 mg daily. 1

Initial Restart Dosing

• Start with 2.5-5 mg orally once daily at bedtime rather than immediately resuming the previous 15 mg daily dose 1
• The 3-month gap represents a complete washout period (olanzapine half-life is 21-54 hours, mean 33 hours), meaning the patient should be treated as if starting fresh 2
• Bedtime administration is preferred because it minimizes daytime sedation and leverages olanzapine's sedating properties for sleep 3, 1

Rationale for Conservative Restart

After 3 months off olanzapine, the patient has lost any tolerance to side effects that may have developed during chronic use. Key safety concerns with immediate full-dose resumption include:

• Orthostatic hypotension risk is highest during initial dosing and dose escalation 1
• Excessive sedation and drowsiness are common side effects that may be more pronounced without prior tolerance 1
• Fall risk is elevated, particularly if this is an elderly patient 1

Titration Schedule

Week 1: Start 2.5-5 mg at bedtime 1

Week 2: If tolerated, increase to 7.5-10 mg at bedtime 1

Week 3: If needed, increase to 15 mg at bedtime (or split as 5 mg AM + 10 mg HS if the previous regimen worked well) 1

• Do not increase doses more frequently than every 1 week, as steady-state concentrations require approximately one week to achieve 1
• The previous split-dosing regimen (5 mg AM + 10 mg HS) can be resumed once the total daily dose reaches 15 mg, but consolidating to bedtime-only dosing (15 mg HS) may improve adherence and minimize daytime sedation 3, 1

Special Considerations

Patient-Specific Factors Requiring Lower Starting Dose (2.5 mg):

• Elderly patients (maximum 10 mg/day in elderly) 1
• Hepatic impairment 1
• Frailty or high fall risk 1
• Concurrent benzodiazepine use (fatalities reported with combined use due to respiratory depression) 1

Monitoring During Titration:

• Orthostatic vital signs at baseline and during dose increases 1
• Sedation and fall risk daily, especially in elderly patients 1
• Metabolic parameters (weight, glucose, lipids) as approximately 40% of patients experience weight gain 1

Common Pitfalls to Avoid

• Do not restart at the previous full dose of 15 mg daily without titration, as this significantly increases risk of orthostatic hypotension, excessive sedation, and falls 1
• Avoid combining with metoclopramide, phenothiazines, or haloperidol during restart to prevent excessive dopamine blockade 1
• Do not use benzodiazepines concurrently without extreme caution and lowest effective doses, given reported fatalities 1
• Do not titrate faster than weekly intervals, as steady-state requires approximately one week 1

Reassessment Timeline

• Evaluate therapeutic response after 4 weeks at the target dose before considering the medication ineffective 1
• After 9 months of stable dosing, consider dosage reduction to reassess ongoing need for medication 1