What is the preferred oral alternative, oral paliperidone (Invega) or risperidone (Risperdal), for a patient previously stable on Long-Acting Injectable (LAI) paliperidone (Invega)?

Oral Paliperidone vs Risperidone for a Patient Previously Stable on LAI Paliperidone

For patients previously stable on long-acting injectable (LAI) paliperidone, oral paliperidone is the preferred oral alternative over risperidone due to its identical active metabolite and more predictable pharmacokinetic profile.

Pharmacological Rationale

• Paliperidone (9-hydroxyrisperidone) is the active metabolite of risperidone, making paliperidone a more direct continuation of the patient's previous treatment 1
• Risperidone requires conversion to paliperidone through CYP2D6 metabolism, introducing potential variability in therapeutic response due to genetic polymorphisms 2
• Oral paliperidone provides more consistent plasma levels compared to risperidone, which may be particularly important for patients transitioning from a stable LAI regimen 3

Clinical Evidence Supporting This Recommendation

• Patients switching from risperidone LAI to paliperidone have shown fewer relapse events (26 vs. 32), longer time to relapse (mean 70 vs. 47 days), and lower overall risk of relapse (hazard ratio 0.54) compared to switching to oral antipsychotics 4
• Case reports document psychosis induced specifically by switching from risperidone to paliperidone in patients with CYP2D6 polymorphisms, suggesting that the medications are not always clinically interchangeable despite their pharmacological relationship 2
• The British Journal of Psychiatry guidelines recommend that when transitioning from LAI to oral medication, maintaining the same active compound is preferred to minimize risk of relapse 5

Practical Implementation

• No oral supplementation is required when switching from paliperidone LAI to oral paliperidone 3
• Initiate oral paliperidone at the time of what would have been the next scheduled injection of paliperidone LAI 3
• Dosing equivalence: Paliperidone LAI 117 mg monthly is approximately equivalent to 6 mg daily oral paliperidone 6

Special Considerations

• For patients with renal impairment, dosage adjustment is required for oral paliperidone but not always for risperidone, which may influence the choice in certain clinical scenarios 6
• If the patient was previously on a high dose of paliperidone LAI (>150 mg monthly), consider bridging with oral paliperidone for at least 7 days to maintain therapeutic levels 7
• Monitor closely for signs of psychotic relapse during and after the transition, being prepared to reinstate antipsychotic treatment immediately if symptoms emerge 8

Potential Pitfalls to Avoid

• Avoid assuming risperidone and paliperidone are clinically interchangeable for all patients despite their pharmacological relationship 2
• Be aware that CYP2D6 genetic polymorphisms can cause significant variability in how patients metabolize risperidone to paliperidone, potentially affecting clinical response 2
• Do not abruptly discontinue LAI paliperidone without establishing therapeutic levels of the oral medication first 5

By maintaining the same active compound (paliperidone) when transitioning from LAI to oral formulation, you can minimize the risk of relapse and maintain the clinical stability previously achieved with the LAI formulation.