What are the considerations for increasing the dose of Invega Sustenna (paliperidone) in an adult patient with a psychiatric condition, such as schizophrenia, who is currently receiving 234mg intramuscularly (IM) and is due for their next dose?

Dose Increase Considerations for Invega Sustenna 234mg IM

For a patient currently on Invega Sustenna 234mg IM who is due for their next dose, increasing beyond 234mg is not recommended as this represents the maximum approved monthly maintenance dose. 1, 2, 3

Current Dosing Context

Your patient is receiving 234mg (150mg eq. paliperidone), which is already the highest approved monthly maintenance dose for Invega Sustenna. 2, 3 The approved maintenance dosing range is 39-234mg (25-150mg eq. paliperidone), with 117mg (75mg eq. paliperidone) being the recommended standard maintenance dose. 3

Why Dose Escalation Beyond 234mg is Not Appropriate

• No approved doses exist above 234mg monthly for Invega Sustenna, as this formulation is designed with a maximum ceiling dose based on safety and efficacy data. 2, 3
• Transient excursions above therapeutic plasma concentrations are associated with increased risk of adverse effects including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms. 4
• The biphasic pharmacokinetic profile of paliperidone palmitate means that increasing dose beyond approved limits could result in clinically dangerous plasma concentration spikes during the initial zero-order absorption phase. 4

Alternative Strategies When 234mg Monthly is Insufficient

Option 1: Verify Adequate Trial Duration

• Ensure the patient has received at least 6-8 weeks at the current 234mg dose before concluding inadequate response, as steady-state concentrations and full therapeutic effects may not be apparent earlier. 5
• Confirm medication adherence by verifying injection administration dates and checking for missed doses. 5

Option 2: Add Oral Supplementation

• Consider adding oral paliperidone extended-release 3-12mg daily to augment the LAI if symptoms persist despite maximum monthly dosing. 6
• Alternatively, add a mood stabilizer (lithium or valproate) if treating bipolar disorder with psychotic features, as combination therapy provides superior efficacy compared to antipsychotic monotherapy. 5

Option 3: Switch to More Frequent Dosing Formulation

• Transition to Invega Trinza (PP3M) if the patient has been stable on monthly injections for at least 4 months, which provides more sustained plasma levels and may improve symptom control. 7
• For patients requiring even more sustained coverage, Invega Hafyera (PP6M) is now available for once-every-6-months administration after stabilization on PP3M. 7

Option 4: Augmentation with Another Antipsychotic

• Add aripiprazole 5-15mg daily as augmentation, which has shown efficacy when combined with other antipsychotics and has a favorable metabolic profile. 5, 8
• Consider low-dose risperidone 0.5-2mg daily as augmentation, though monitor carefully for additive prolactin elevation given paliperidone's mechanism. 8

Option 5: Switch to Different Antipsychotic

• If the patient has failed adequate trial at maximum paliperidone palmitate dosing, consider switching to clozapine for treatment-resistant schizophrenia, which requires routine laboratory monitoring. 5
• Alternatively, switch to another long-acting injectable such as risperidone LAI or aripiprazole LAI if tolerability issues exist with paliperidone. 2

Critical Monitoring if Pursuing Augmentation

• Baseline metabolic assessment including BMI, waist circumference, blood pressure, fasting glucose, and lipid panel before adding any medication. 5
• Monitor for extrapyramidal symptoms more frequently with antipsychotic polypharmacy, as risk increases with combined dopamine blockade. 9
• Check prolactin levels if adding another antipsychotic to paliperidone, as hyperprolactinemia risk is already elevated with paliperidone monotherapy. 2, 6
• Assess for drug-drug interactions particularly if adding medications metabolized by CYP2D6, though paliperidone itself has minimal enzymatic metabolism. 6

Common Pitfalls to Avoid

• Never exceed 234mg monthly dosing of Invega Sustenna, as no safety or efficacy data exist for higher doses and adverse effect risk increases substantially. 2, 4
• Avoid premature dose escalation before completing an adequate 6-8 week trial at therapeutic doses, as this leads to unnecessary polypharmacy and increased side effect burden. 5
• Do not add antidepressants without mood stabilizers if treating bipolar disorder, as this risks mood destabilization and mania induction. 5
• Avoid combining multiple high-potency antipsychotics without clear rationale, as this dramatically increases extrapyramidal symptom risk and metabolic complications without proven added benefit. 9