What olanzapine (Zyprexa) dose should be started for an adult male currently on paliperidone (Invega) 6 mg daily?

Olanzapine Dosing When Switching from Paliperidone 6 mg

Start olanzapine at 10 mg once daily at bedtime when switching from paliperidone 6 mg, using a cross-taper strategy where you gradually reduce paliperidone over 1-2 weeks while maintaining the full olanzapine dose. 1, 2

Rationale for 10 mg Starting Dose

• Paliperidone 6 mg is approximately equivalent to risperidone 4-6 mg daily, and when switching from risperidone to olanzapine, higher doses of the new antipsychotic are typically required to maintain therapeutic effect 2
• The standard therapeutic dose of olanzapine for schizophrenia is 10 mg/day, which represents the target dose for most patients with established psychotic illness 1
• Starting at 2.5-5 mg would only be appropriate for elderly patients, those with hepatic impairment, or patients with significant frailty—none of which apply to your adult male patient 1, 3

Cross-Tapering Strategy (Preferred Approach)

Week 1:

• Start olanzapine 10 mg at bedtime 1
• Continue paliperidone 6 mg daily (100% of current dose) 2

Week 2:

• Continue olanzapine 10 mg at bedtime 1
• Reduce paliperidone to 3 mg daily (50% of current dose) 2

Week 3 onward:

• Continue olanzapine 10 mg at bedtime 1
• Discontinue paliperidone completely 2

Why Cross-Tapering Over Abrupt Switch

• Cross-tapering reduces the risk of rebound psychotic symptoms and withdrawal effects compared to abrupt discontinuation 4, 2
• Research demonstrates that gradual reduction of the pre-switch antipsychotic over 2 weeks results in higher treatment retention rates (88% vs 72-75% with faster switches) 4
• Paliperidone has minimal sedative and anticholinergic activity, so a 2-week taper is sufficient—longer tapers are only needed for highly sedating or anticholinergic agents 2

Important Monitoring During the Switch

• Monitor for extrapyramidal symptoms (EPS) improvement: Paliperidone causes EPS in approximately 25% of patients at therapeutic doses, while olanzapine has significantly lower EPS risk 5, 6
• Watch for increased sedation: Olanzapine is more sedating than paliperidone, particularly in the first 1-2 weeks; bedtime dosing minimizes daytime impairment 1
• Monitor weight and metabolic parameters: Olanzapine causes clinically significant weight gain (≥7%) in approximately 40% of patients, compared to 8-15% with paliperidone 6, 7
• Check orthostatic vital signs: Olanzapine can cause orthostatic hypotension, especially during dose initiation 1, 3

Dose Adjustments After Initial Switch

• Maintain 10 mg/day for at least 4 weeks before considering dose adjustments, as this is the minimum time needed to assess therapeutic response 1
• If inadequate response after 4 weeks, increase to 15 mg daily; maximum dose is 20 mg/day, though most patients respond to 10-15 mg 1
• If excessive sedation occurs, consider reducing to 7.5 mg daily rather than switching medications 1

Common Pitfalls to Avoid

• Do not start at 2.5-5 mg in a non-elderly adult male: This dose is subtherapeutic for schizophrenia and increases the risk of relapse during the switch 1
• Do not abruptly discontinue paliperidone: This increases discontinuation rates by approximately 50% compared to gradual tapering 4
• Do not combine with benzodiazepines at high doses: Fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine due to respiratory depression 1, 3
• Do not ignore metabolic monitoring: Approximately 40% of patients gain significant weight on olanzapine; consider prophylactic metformin if metabolic risk factors are present 1