How to switch from Risperidone (risperidone) 2 mg bid to Abilify (aripiprazole)?

Switching from Risperidone 2 mg BID to Aripiprazole

The recommended approach for switching from risperidone 2 mg twice daily to aripiprazole is to start with aripiprazole 10 mg once daily while gradually tapering risperidone over 1-2 weeks to minimize the risk of withdrawal symptoms or psychotic exacerbation.

Switching Protocol

Step 1: Initiation of Aripiprazole

• Start aripiprazole at 10 mg once daily (FDA recommended starting dose) 1
• Continue full dose of risperidone (2 mg BID) for the first 2-3 days

Step 2: Gradual Tapering of Risperidone

• Days 4-7: Reduce risperidone to 1.5 mg BID while maintaining aripiprazole at 10 mg daily
• Days 8-11: Further reduce risperidone to 1 mg BID
• Days 12-14: Reduce risperidone to 0.5 mg BID
• After day 14: Discontinue risperidone completely

Step 3: Aripiprazole Dose Adjustment

• After risperidone is completely discontinued, assess clinical response to aripiprazole
• If needed, aripiprazole can be titrated up to 15-30 mg daily based on efficacy and tolerability 1
• Allow at least 2 weeks between dose adjustments to reach steady-state levels

Rationale for This Approach

The cross-titration method is preferred over abrupt switching because:

1. It minimizes the risk of withdrawal symptoms from risperidone
2. It prevents a gap in dopamine receptor occupancy that could lead to psychotic exacerbation
3. It allows for gradual adaptation to the different receptor binding profiles of the two medications

Aripiprazole has a unique partial agonist activity at D2 receptors, unlike risperidone which is a full antagonist 2. This pharmacological difference necessitates a careful transition to prevent destabilization of symptoms.

Special Considerations

Potential Drug Interactions

• If the patient is taking strong CYP3A4 inhibitors (e.g., ketoconazole) or CYP2D6 inhibitors (e.g., fluoxetine), the aripiprazole dose should be reduced by 50% 1
• For known CYP2D6 poor metabolizers, start with half the usual aripiprazole dose (5 mg) 1

Monitoring During Transition

• Monitor closely for:
  • Psychotic symptom exacerbation (particularly in the first 2 weeks)
  • Extrapyramidal symptoms (EPS)
  • Akathisia (more common with aripiprazole)
  • Sleep disturbances (may be more prominent with aripiprazole) 3

Advantages of Switching

• Aripiprazole may help resolve risperidone-induced hyperprolactinemia 4
• Aripiprazole typically has less weight gain and metabolic effects compared to risperidone
• Once-daily dosing with aripiprazole may improve adherence compared to twice-daily risperidone

Potential Pitfalls and How to Avoid Them

1. Psychotic exacerbation: Cases of severe psychotic exacerbation have been reported when switching from risperidone to aripiprazole 2. This risk can be minimized by:

   • Using the gradual cross-titration approach rather than abrupt switching
   • Maintaining adequate dopamine blockade during the transition
   • Close monitoring during the first 2-3 weeks of the switch

2. Akathisia: Aripiprazole can cause akathisia, which may be mistaken for anxiety or agitation. If this occurs:

   • Consider temporary dose reduction of aripiprazole
   • Beta-blockers (e.g., propranolol) may be helpful for management 5

3. Sleep disturbances: Aripiprazole is less sedating than risperidone and may cause insomnia initially. Consider:

   • Morning administration of aripiprazole
   • Temporary use of a hypnotic if needed

4. Withdrawal symptoms: Too rapid discontinuation of risperidone can lead to withdrawal symptoms. The gradual taper over 2 weeks helps prevent this complication.

By following this structured approach, the transition from risperidone to aripiprazole can be accomplished safely while maintaining symptom control and minimizing adverse effects.