Switching from Olanzapine 20mg Daily to Quetiapine 150mg Nightly
Use a gradual 2-week cross-titration strategy: continue olanzapine at full dose (10mg twice daily) for week 1 while starting quetiapine, reduce olanzapine to 50% (10mg once daily) in week 2, then discontinue olanzapine completely at the start of week 3. 1, 2
Recommended Cross-Titration Schedule
Week 1
- Continue olanzapine 10mg twice daily (full dose) 2
- Start quetiapine 12.5mg at bedtime on day 1 3, 4
- Titrate quetiapine rapidly: 25mg on day 2, 50mg on day 3, 100mg on day 4, 150mg on day 5 5
- This maintains antipsychotic coverage while establishing therapeutic quetiapine levels 1
Week 2
- Reduce olanzapine to 10mg once daily (50% of original dose) 2
- Continue quetiapine 150mg at bedtime 4
- Monitor closely for breakthrough psychotic symptoms or withdrawal effects 1
Week 3 Onward
Evidence Supporting This Approach
The gradual 2-week reduction strategy has the strongest evidence base. A randomized controlled trial comparing three olanzapine discontinuation strategies when switching to risperidone found that maintaining olanzapine at 100% dose for week 1, then 50% for week 2 before discontinuation resulted in the lowest treatment discontinuation rate (12%) compared to abrupt switching (25%) or faster tapering (28%). 2 The relative risk of early discontinuation was 0.77 (95% CI 0.61-0.99) favoring the slower taper. 2
This gradual approach is particularly important because abrupt quetiapine discontinuation can cause rebound insomnia, agitation, and symptom relapse. 1 The 2-week overlap provides adequate time for quetiapine to reach steady-state while preventing destabilization. 1
Critical Monitoring Parameters
During Cross-Titration (Weeks 1-3)
- Monitor for orthostatic hypotension daily during week 1 - quetiapine is more sedating and causes transient orthostasis, especially during initial titration 3, 4, 1
- Check orthostatic vital signs (lying and standing blood pressure) before each dose increase 1
- Assess for breakthrough psychotic symptoms - positive symptoms (hallucinations, delusions) or negative symptoms indicating inadequate antipsychotic coverage 1
- Monitor for extrapyramidal symptoms - though less likely with this switch direction, assess for akathisia, dystonia, and rigidity 1
Ongoing Monitoring (Weeks 4-12)
- Weight and metabolic parameters at 4,8, and 12 weeks - both medications affect metabolism, though patients typically lose weight when switching from olanzapine 1, 6
- Fasting glucose and lipid panel - metabolic dysfunction occurs more commonly with olanzapine than quetiapine 6
- Sedation assessment - quetiapine causes more sedation than olanzapine; if excessive daytime sedation occurs, adjust timing rather than adding stimulants 3, 1
Common Pitfalls to Avoid
Do not abruptly discontinue olanzapine - this increases risk of treatment discontinuation by more than 2-fold compared to gradual tapering. 2 Abrupt cessation can cause symptom relapse and withdrawal effects. 1
Do not exceed quetiapine 200mg twice daily (400mg total) - the maximum recommended dose is 200mg twice daily, though 150mg nightly may be sufficient for maintenance. 3, 4 Your target dose of 150mg nightly is appropriate and conservative. 4
Do not add stimulants for sedation during cross-titration - if morning grogginess occurs, adjust the quetiapine dose schedule or timing rather than adding methylphenidate or modafinil. 1 Consider giving quetiapine earlier in the evening (e.g., 8 PM instead of bedtime) to reduce morning sedation.
Monitor for falls risk - both medications cause orthostatic hypotension, and the risk is additive during overlap periods, particularly in elderly patients. 1 This is especially critical during week 1 when both medications are at full/near-full doses.
Special Considerations for Elderly Patients
If this patient is elderly, use a more conservative approach: start quetiapine at 12.5mg nightly and increase by 12.5-25mg every 2-3 days rather than daily. 3 The maximum dose in elderly patients should not exceed 200mg daily total. 3 Elderly patients are at higher risk for orthostatic hypotension, falls, and sedation with both medications. 3, 1
When to Reassess the Switch
If breakthrough psychotic symptoms emerge during weeks 1-2, do not accelerate the olanzapine taper - instead, consider temporarily increasing the quetiapine dose within the safe range (up to 200mg nightly) while maintaining the planned olanzapine taper schedule. 1, 5 If symptoms persist beyond week 3, the target quetiapine dose of 150mg may be insufficient, and titration to 200-300mg nightly may be necessary. 5