What is the recommended protocol for cross-tapering from Seroquel (quetiapine) to olanzapine?

Cross-Tapering from Quetiapine (Seroquel) to Olanzapine

The most effective protocol for cross-tapering from quetiapine to olanzapine is a gradual reduction of quetiapine over 2 weeks while simultaneously initiating olanzapine at a low dose and gradually increasing it to the target dose.

Recommended Cross-Tapering Protocol

Step 1: Initiation (Week 1)

• Start olanzapine at 2.5-5 mg once daily (preferably at bedtime)
• Continue quetiapine at 100% of the original dose for the first week
• Monitor for sedation, orthostatic hypotension, and other side effects

Step 2: Transition (Week 2)

• Increase olanzapine to target dose (typically 5-10 mg/day for most indications)
• Reduce quetiapine to 50% of the original dose
• Continue monitoring for side effects and clinical response

Step 3: Completion (Week 3)

• Discontinue quetiapine completely
• Continue olanzapine at the established target dose
• Assess clinical response and adjust olanzapine dose if needed

Evidence Supporting This Approach

Research evidence supports that a gradual cross-tapering strategy over 2 weeks is associated with higher rates of treatment retention and fewer discontinuations compared to more abrupt switching strategies 1. The gradual approach minimizes withdrawal symptoms, rebound effects, and adverse events that might occur with abrupt discontinuation.

Dosing Considerations

Olanzapine Starting Dose:

• For most adults: 2.5-5 mg once daily 2
• For elderly patients or those with hepatic impairment: Start with 2.5 mg 2
• Available as oral tablets or orally disintegrating tablets (ODT) 2

Target Olanzapine Dose:

• Typical maintenance dose: 5-20 mg daily 2
• Adjust based on clinical response and tolerability

Special Considerations and Monitoring

Potential Side Effects to Monitor:

1. Sedation/drowsiness: Both medications cause sedation, but the effect may differ between agents
2. Orthostatic hypotension: Particularly during the transition period
3. Metabolic effects: Monitor weight, blood glucose, and lipids
4. Extrapyramidal symptoms: Less common with these atypical antipsychotics but should be monitored

Important Precautions:

• Avoid combining with benzodiazepines when possible due to risk of oversedation and respiratory depression 2
• Use caution in elderly patients due to increased sensitivity to side effects 2
• Be aware that both medications can cause QTc prolongation, though to different degrees

Clinical Pearls

• The cross-tapering period may need to be extended beyond 2 weeks for patients on high doses of quetiapine (>600 mg/day)
• Morning sedation may decrease when switching from quetiapine to olanzapine due to differences in half-life
• Sexual dysfunction may be less severe with quetiapine compared to olanzapine 3, so monitor for changes in sexual function during the switch
• If excessive sedation occurs during cross-tapering, consider administering olanzapine at bedtime and quetiapine doses earlier in the day
• For patients with acute agitation during the transition, temporary dose adjustments may be needed 4

This cross-tapering protocol balances the need to maintain symptom control while minimizing adverse effects during the transition between these two atypical antipsychotics.