Can Risperidone (risperidone) 4mg oral be discontinued on the same day as administering the second dose of Paliperidone (paliperidone) 75mg intramuscularly (IM)?

Discontinuing Oral Risperidone When Initiating Paliperidone Palmitate

Yes, oral risperidone 4mg can be discontinued on the same day as the second dose of paliperidone palmitate 75mg IM, as no oral supplementation is required with the approved paliperidone palmitate initiation regimen. 1

Rationale for Same-Day Discontinuation

The FDA-approved initiation regimen for paliperidone palmitate (150mg equivalent on day 1, followed by 100mg equivalent on day 8) was specifically designed to achieve therapeutic plasma concentrations rapidly without requiring oral antipsychotic supplementation. 1 This loading dose strategy eliminates the need for oral bridging therapy in most patients.

Paliperidone palmitate can be initiated the day after discontinuing previous oral antipsychotic treatment, and when switching from oral risperidone specifically, the long-acting injection should begin at the time of discontinuation. 1

Important Clinical Context

Pharmacokinetic Considerations

• Oral risperidone reaches peak clinical effects at 3-4 hours with a duration of action of 6-8 hours 2, meaning the medication clears relatively quickly from the system
• The paliperidone palmitate loading dose regimen (day 1 and day 8 deltoid injections) was designed through population pharmacokinetic modeling to achieve adequate plasma concentrations immediately without oral supplementation 1

Exception: Higher Dose Risperidone

However, there is one critical caveat: Research suggests that patients on risperidone ≥4mg/day may benefit from oral bridging therapy when switching to paliperidone palmitate. 3

• A study found statistically significant reductions in hospitalization days in patients on risperidone ≥4mg/day who were bridged with oral risperidone for ≥7 days after the first paliperidone injection compared to those who were not bridged 3
• Since your patient is on exactly 4mg risperidone, this represents the threshold dose where bridging may be beneficial

Practical Recommendation Algorithm

For your specific case (risperidone 4mg at the second paliperidone dose):

1. At the second paliperidone injection (day 8): You can safely discontinue oral risperidone the same day, as the loading doses should provide adequate coverage 1

2. Alternative conservative approach: Consider continuing risperidone 4mg for 7 days after the second paliperidone injection if the patient has a history of rapid decompensation or is at high risk for relapse 3

3. Monitor closely: Watch for breakthrough psychotic symptoms, agitation, or behavioral changes in the first 2-4 weeks after discontinuation 3

Common Pitfalls to Avoid

• Do not continue oral risperidone indefinitely "just to be safe" - this defeats the purpose of long-acting injectable therapy and increases side effect burden 1
• Do not assume all patients need bridging - the majority of patients switching from oral antipsychotics to paliperidone palmitate do not require oral supplementation with the approved loading dose regimen 1
• Monitor for extrapyramidal symptoms - risperidone 4mg is at the threshold where EPS can occur, and the transition period may temporarily alter side effect profiles 4