How to switch a patient from Olanzapine to Risperidone and then to Paliperidone (Invega) depot?

Switching from Olanzapine to Risperidone to Paliperidone Depot

Use a gradual cross-tapering approach over 2 weeks when switching from olanzapine to risperidone, then bridge with oral risperidone for at least 7 days after initiating paliperidone depot if the patient is on ≥4 mg/day risperidone. 1, 2, 3

Step 1: Switch from Olanzapine to Risperidone

Implement a 2-week gradual cross-taper strategy to minimize discontinuation risk and maintain symptom control:

• Week 1: Continue olanzapine at 100% of current dose while initiating risperidone at target therapeutic dose 2
• Week 2: Reduce olanzapine to 50% of entry dose while continuing risperidone 2
• Week 3 onward: Discontinue olanzapine completely 2

This gradual 2-week reduction strategy has the lowest all-cause treatment discontinuation rate (12%) compared to abrupt switching (25%) or faster tapering (28%), with a relative risk of early discontinuation of 0.77 (CI 0.61-0.99) 2. The gradual approach allows time for risperidone to reach therapeutic levels while preventing olanzapine withdrawal symptoms and maintaining receptor coverage during the transition 1.

Monitor for symptom worsening during the switch, as improvements in positive symptoms and anxiety typically occur but require 4-6 weeks to fully manifest 2, 1.

Step 2: Transition from Risperidone to Paliperidone Depot

Determine if bridging with oral risperidone is necessary based on the patient's current risperidone dose:

For patients on risperidone ≥4 mg/day:

• Continue oral risperidone for at least 7 days after the first paliperidone depot injection 3
• This bridging strategy is associated with statistically significant reductions in hospitalization days compared to non-bridged patients 3
• The package insert does not recommend bridging, but clinical evidence demonstrates that patients on higher risperidone doses may have inadequate serum concentrations without it 3

For patients on risperidone <4 mg/day:

• Paliperidone depot can be initiated without oral bridging, as the loading dose strategy provides adequate coverage 3

Paliperidone Depot Dosing Strategy

Initiate paliperidone palmitate using the standard loading dose regimen:

• Day 1: 234 mg deltoid injection 4
• Day 8: 156 mg deltoid injection 4
• Maintenance (Day 36 onward): 117 mg monthly (range 39-234 mg), adjusted based on efficacy and tolerability 4

Consider higher maintenance doses (156-234 mg monthly) if:

• The patient required higher risperidone doses (≥6 mg/day) for symptom control 4
• Acute symptoms are present 4
• Previous antipsychotic showed insufficient efficacy 4

Consider lower maintenance doses (39-78 mg monthly) if:

• The patient is recently diagnosed 4
• Previous tolerability issues occurred with other antipsychotics 4
• Renal impairment is present 4

Critical Dosing Consideration

When switching from risperidone to paliperidone ER/depot, higher doses of paliperidone may be required compared to the risperidone dose due to differences in bioavailability and receptor binding profiles 4. Paliperidone is the active metabolite of risperidone, but direct dose equivalence does not apply.

Common Pitfalls to Avoid

• Abrupt olanzapine discontinuation: This doubles the risk of treatment discontinuation compared to gradual tapering 2
• Failing to bridge patients on higher risperidone doses: Patients on ≥4 mg/day risperidone without bridging have significantly more hospitalization days 3
• Switching too quickly: Allow 4 weeks minimum to assess response at each stage before declaring treatment failure 1
• Inadequate paliperidone dosing: The standard 117 mg maintenance dose may be insufficient for patients previously requiring higher risperidone doses 4

Monitoring During Transitions

• Watch for extrapyramidal symptoms during the olanzapine-to-risperidone switch, as risperidone has higher D2 antagonism 2
• Assess for withdrawal symptoms from olanzapine, particularly anticholinergic rebound effects 4
• Monitor weight changes, as switching from olanzapine may result in weight stabilization or loss 2
• Evaluate symptom control at weeks 2,4, and 6 after each medication change 1, 2