What is the difference between Invega Sustenna (paliperidone palmitate) and Invega (paliperidone) for treating schizophrenia?

Invega vs Invega Sustenna: Key Differences

Invega Sustenna (paliperidone palmitate) is a long-acting injectable formulation that should be preferred over oral Invega (paliperidone) for patients with a history of poor or uncertain adherence, as it directly addresses the primary cause of relapse in schizophrenia. 1

Formulation and Administration

Oral Invega (Paliperidone ER):

• Extended-release oral tablet taken once daily 2
• Provides stable plasma concentrations over 24 hours 2
• Can be initiated at therapeutically effective dosages (3-12 mg/day) without titration 2
• Requires daily patient adherence 2

Invega Sustenna (Paliperidone Palmitate):

• Long-acting injectable (LAI) administered intramuscularly once monthly 3
• Dosing range: 25-150 mg equivalents 3
• Recommended initiation: 150 mg eq. deltoid injection on day 1, followed by monthly maintenance dosing 3
• Onset of clinical response within 8 days when using recommended initiation regimen 3

Clinical Efficacy

Both formulations demonstrate comparable efficacy in reducing PANSS total scores and treating positive and negative symptoms of schizophrenia 2, 3. The oral formulation showed significant improvement in PANSS scores after 4 days in some trials 2, while the injectable formulation demonstrated clinical response within 8 days 3.

Critical efficacy advantage of Invega Sustenna: In a 24-week maintenance trial, the injectable formulation was associated with significantly longer time to relapse compared to placebo, leading to early study termination due to favorable results 3. This directly impacts the most important clinical outcomes—preventing relapse reduces morbidity and preserves functional capacity.

Adherence and Real-World Outcomes

The American Psychiatric Association suggests (2B) that patients receive treatment with a long-acting injectable antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence. 1

This recommendation is critical because:

• Medication nonadherence is the primary driver of symptomatic relapse in schizophrenia 4
• Each relapse worsens prognosis and increases disease burden 4
• Adherence improves with decreased dosing frequency 4
• LAIs eliminate the daily decision-making required with oral medications 1

Tolerability Profile

Both formulations share similar tolerability profiles, as Invega Sustenna contains the same active metabolite as oral Invega 3. Common considerations include:

• Extrapyramidal symptoms occur in approximately 25% of patients at higher doses (9-12 mg/day oral; mean 10 mg/day injectable) 2, 3
• Elevated plasma prolactin levels with both formulations 2
• Minimal effects on glucose, lipid, or insulin levels 2
• Clinically significant weight gain in approximately 15% of patients 2
• Unique to injectable: Injection site reactions 3

Extended Formulation Options

For patients stabilized on monthly Invega Sustenna, longer-acting formulations are available:

• PP3M (Invega Trinza): Once every 3 months, requiring minimum 4 months stability on PP1M 4, 5
• PP6M (Invega Hafyera): Once every 6 months, further reducing administration frequency 6

These extended formulations improve adherence and decrease relapse/hospitalization rates while maintaining comparable efficacy and safety 4, 6.

Clinical Decision Algorithm

Choose Invega Sustenna (LAI) when:

• Patient has documented history of medication nonadherence 1
• Previous relapses related to stopping oral medications 1
• Patient preference for less frequent dosing 1
• Need for objective confirmation of medication delivery 1

Choose oral Invega when:

• Patient demonstrates reliable adherence to daily oral medications 2
• Patient refuses injectable formulations 2
• Initial stabilization phase where rapid dose adjustments may be needed 2

Critical Pitfall to Avoid

Do not underutilize long-acting injectables. 1 LAIs remain underutilized despite frequent nonadherence with oral medications and subsequent relapse 1. The evidence clearly demonstrates that LAIs should be considered earlier in treatment, not reserved only for patients who have already experienced multiple relapses due to nonadherence 1.