Do you discontinue olanzapine (an atypical antipsychotic) abruptly when switching to risperidone (an atypical antipsychotic)?

Switching from Olanzapine to Risperidone: Gradual Cross-Tapering is Strongly Recommended

When switching from olanzapine to risperidone, you should NOT discontinue olanzapine abruptly—instead, implement a gradual 2-week cross-taper while initiating risperidone at the target therapeutic dose. This approach minimizes treatment discontinuation and withdrawal symptoms while maintaining symptom control.

Evidence-Based Cross-Tapering Protocol

The optimal switching strategy involves maintaining olanzapine at 100% of the entry dose for the first week after starting risperidone, then reducing to 50% for the second week before complete discontinuation. 1 This gradual 2-week taper resulted in only 12% treatment discontinuation compared to 25-28% with abrupt or faster discontinuation strategies. 2

Week-by-Week Implementation:

• Week 1: Start risperidone at target dose (typically 2 mg/day for first-episode psychosis, 0.5-2 mg/day depending on clinical context) while continuing olanzapine at 100% of current dose 1, 3
• Week 2: Reduce olanzapine to 50% of entry dose while maintaining risperidone 1
• Week 3 onward: Discontinue olanzapine completely 1

The relative risk of early discontinuation was 0.77 (95% CI: 0.61-0.99) for the slowest dose reduction compared with faster strategies. 2

Risperidone Dosing Considerations

Start risperidone at the target therapeutic dose immediately, not at a low dose requiring titration. 1 For most patients with schizophrenia, this means 2 mg/day. 4, 3

Key dosing parameters:

• Maximum effective dose: 4-6 mg/day; doses above 6 mg/day increase extrapyramidal symptoms without additional benefit 1, 3
• Elderly or frail patients: Reduce starting dose to 0.25-0.5 mg/day 1, 3
• Consider split dosing (e.g., 2 mg at night + 1 mg in morning) to reduce peak plasma concentrations and minimize side effects like orthostatic hypotension 3

Critical Safety Considerations

Abrupt discontinuation of olanzapine can precipitate serious withdrawal symptoms including dyskinesias, parkinsonian symptoms, dystonias, and potentially neuroleptic malignant syndrome. 1 This constitutes unacceptable medical care. 5

Monitor for Withdrawal Symptoms:

• Insomnia, anxiety, irritability 5
• Movement disorders (dyskinesias, parkinsonism) 1
• Exacerbation of original psychotic symptoms 5

If withdrawal symptoms emerge during tapering, temporarily return to the previous olanzapine dose and attempt a smaller reduction after symptoms stabilize. 1

Monitoring Requirements During Cross-Taper

Schedule follow-up appointments every 2-4 weeks during the switching period. 1 At each visit, assess:

• Extrapyramidal symptoms: Risperidone carries higher risk than olanzapine, particularly at doses >2 mg/day 1, 3
• Orthostatic hypotension: Common with risperidone, especially problematic in elderly patients 3
• Return of psychotic symptoms: Document baseline symptoms before initiating switch 1
• Metabolic parameters: Weight changes (expect weight loss as olanzapine is discontinued) 2

Common Pitfalls to Avoid

Do not use fixed timelines—adjust the taper based on individual patient response. 1 If the patient experiences symptom worsening or significant withdrawal effects, slow the taper further by:

• Extending time between dose reductions to 4-6 weeks 5
• Using smaller olanzapine dose reductions (e.g., 25% instead of 50%) 5

Avoid combining olanzapine with benzodiazepines during the cross-taper due to risk of oversedation and respiratory depression. 1

Do not abandon the patient if they struggle with the taper—consider pausing at a stable dose rather than pushing forward. 5

Alternative Approach: When Abrupt Switching May Be Necessary

While gradual cross-tapering is strongly preferred, abrupt switching may be required in cases of severe or acute adverse reactions to olanzapine. 6 However, a retrospective study of 58 elderly dementia patients showed that abrupt switching from risperidone to olanzapine (mean doses 1.54 mg and 5.69 mg respectively) did not result in clinical deterioration, though this was in the opposite direction and in a specific population. 7

The evidence overwhelmingly supports gradual cross-tapering as the safer, more effective approach with lower discontinuation rates and better symptom control. 2