Can we discontinue risperidone (oral) on the same day as administering the second dose of paliperidone (Invega) 75 mg intramuscularly (IM) in an adult patient with schizophrenia?

Discontinuing Oral Risperidone with Second Dose of Paliperidone 75 mg IM

Yes, oral risperidone should be discontinued on the same day as the second dose of paliperidone palmitate 75 mg IM, as adequate paliperidone plasma levels are established by this point and continued oral supplementation risks excessive dopamine blockade and dose-dependent adverse effects. 1

Rationale for Discontinuation Timing

• Paliperidone palmitate provides sustained therapeutic plasma concentrations after the second injection, eliminating the need for oral antipsychotic supplementation 2, 3
• The osmotic controlled-release delivery system of paliperidone minimizes peak-trough fluctuations and maintains stable plasma concentrations with once-monthly dosing 3
• Continuing oral risperidone beyond the second paliperidone injection increases risk of extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner 2, 3

Standard Long-Acting Injectable Initiation Protocol

• Oral supplementation is only required during the initial lead-in phase (typically 2 weeks) when transitioning to long-acting injectable formulations 4
• After the loading doses establish therapeutic plasma levels, oral supplementation becomes unnecessary and potentially harmful 4
• Mean plasma concentrations for paliperidone remain stable during monthly dosing without oral supplementation 4

Critical Safety Considerations

• Monitor for extrapyramidal symptoms at every visit, as these predict poor long-term adherence and occur in a dose-dependent manner with both risperidone and paliperidone 5
• Assess for hyperprolactinemia, which occurs at higher rates with paliperidone compared to other atypical antipsychotics 2
• Obtain baseline ECG if cardiac risk factors are present, as both medications can prolong QTc interval 6

Important Caveats

• Individual pharmacogenetic variation in CYP2D6 metabolism may affect the risperidone-to-paliperidone conversion ratio 7
• In rare cases of CYP2D6 polymorphism, patients may have differential responses to risperidone versus paliperidone despite their metabolic relationship 7
• If psychotic symptoms emerge after discontinuing oral risperidone, consider restarting oral supplementation temporarily while reassessing the patient's metabolic phenotype 7

Monitoring Algorithm Post-Discontinuation

• Week 1-2: Assess for withdrawal symptoms or symptom exacerbation; monitor extrapyramidal symptoms
• Week 4: Evaluate PANSS scores and clinical global impression to confirm therapeutic stability 8
• Monthly: Continue monitoring for relapse signs, extrapyramidal symptoms, and metabolic effects 4, 3

1, 4, 2, 3, 7