Risperidone Tapering to Zero
For patients discontinuing risperidone, taper hyperbolically by reducing 10% of the most recent dose every 3-6 months, continuing down to very small final doses (as low as 1/40th of the therapeutic dose) before complete cessation to minimize withdrawal and relapse risk.
Rationale for Hyperbolic Tapering
The hyperbolic tapering approach is critical for risperidone because of the non-linear relationship between dose and dopamine D2 receptor blockade 1. Linear dose reductions create disproportionately large changes in receptor occupancy at lower doses, which can trigger withdrawal symptoms and increase relapse risk 1.
- Each reduction should be 10-25% of the most recent dose (not the original dose), with intervals of 3-6 months between reductions 1
- Some patients may prefer monthly reductions of 10% or less of their most recent dose 1
- This approach allows neuroadaptations (including dopaminergic hypersensitivity) time to resolve, which can persist for months or years after stopping 1
Specific Tapering Schedule Example
For a patient on risperidone 4 mg/day (a common therapeutic dose 2, 3):
- Month 0-3: 4 mg → 3 mg (25% reduction)
- Month 3-6: 3 mg → 2.25 mg (25% reduction)
- Month 6-9: 2.25 mg → 1.7 mg (25% reduction)
- Month 9-12: 1.7 mg → 1.3 mg (25% reduction)
- Continue this pattern down to approximately 0.1 mg before complete cessation 1
The entire process may take 12-24 months or longer to reach zero 1.
Critical Considerations
Never abruptly discontinue risperidone in patients who have been on it long-term, as this creates severe withdrawal risks and dramatically increases relapse probability 1.
- PET imaging shows that risperidone 3 mg/day produces approximately 72% D2 receptor occupancy, while 6 mg/day produces 82% occupancy 3
- The final doses before complete cessation may need to be as small as 1/40th of a therapeutic dose (approximately 0.1 mg for a patient originally on 4 mg) to prevent a large decrease in D2 blockade when stopped 1
- Relapses cluster in the months to years after antipsychotic cessation, suggesting persistent neuroadaptations 1
Monitoring During Tapering
Assess for withdrawal symptoms and early relapse signs after each dose reduction before proceeding to the next step 4:
- Monitor for psychotic symptom recurrence (positive and negative symptoms)
- Watch for extrapyramidal symptoms, which may paradoxically emerge or worsen during tapering
- Screen for anxiety, depression, and sleep disturbances that may emerge 5
- If withdrawal symptoms or early relapse signs appear, return to the previous well-tolerated dose and slow the taper further 4
Adjunctive Support
Consider non-pharmacological support during the tapering process:
- Cognitive behavioral therapy and stress management techniques 4
- Frequent clinical contact (at least monthly) during active tapering 4
- Patient education about the prolonged nature of safe tapering and the rationale for very small final doses
Common Pitfalls to Avoid
Do not use standard "therapeutic minimum dose" approaches (such as tapering to 0.5 mg and then stopping), as these create large drops in receptor occupancy 1, 6.