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paliperidone

Antipsychotic

LAI available

Brands: INVEGA, INVEGA SUSTENNA, INVEGA TRINZA, INVEGA HAFYERA

Published 2026-03-24 · Last reviewed 2026-03-31 · 5 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Antipsychotic·Typical dose: Paliperidone extended-release tablets: start 6 mg once daily; adjust 3–12 mg/day (max 12 mg/day; adolescents start at 3 mg daily).·Half-life: Steady-state mean 23 h·LAI available: Yes

Class: Antipsychotic
Typical dose: Paliperidone extended-release tablets: start 6 mg once daily; adjust 3–12 mg/day (max 12 mg/day; adolescents start at 3 mg daily).
Half-life: Steady-state mean 23 h
LAI available: Yes

Quick answers

What is paliperidone?: Paliperidone (brand Invega) is the active metabolite of risperidone, delivered as extended-release tablets and long-acting injectable palmitate formulations for schizophrenia and schizoaffective disorder.
What is INVEGA?: INVEGA is a brand name for paliperidone (other brands: INVEGA SUSTENNA, INVEGA TRINZA, INVEGA HAFYERA).
What is INVEGA (paliperidone) used for?: Label indications include: Schizophrenia; schizoaffective disorder.
What drug class is INVEGA (paliperidone)?: Atypical Antipsychotic.
What is the mechanism of action of INVEGA (paliperidone)?: D2 and 5‑HT2A antagonism; active metabolite of risperidone.
What strengths does INVEGA (paliperidone) come in?: Paliperidone extended-release (OROS) tablets: 1.5 mg, 3 mg, 6 mg, 9 mg, 12 mg once daily without cyclic titration.
Is INVEGA (paliperidone) a controlled substance?: No — it is not scheduled as a controlled substance under U.S. federal law.
What is INVEGA (paliperidone) dosing for schizophrenia?: Schizophrenia (adults): start 6 mg ER once daily; adjust 3–12 mg/day. Adolescents start 3 mg once daily (max 12 mg/day).
How is paliperidone started as a long-acting injectable (LAI)?: Invega Sustenna: loading 234 mg (day 1 deltoid) and 156 mg (day 8 deltoid) then 39–234 mg monthly (max 234 mg monthly).

General information

Paliperidone (brand Invega) is the active metabolite of risperidone, delivered as extended-release tablets and long-acting injectable palmitate formulations for schizophrenia and schizoaffective disorder.

Paliperidone mechanism of action centers on dopamine D2 and serotonin 5-HT2A antagonism, mirroring risperidone while adding α1/α2 and H1 blockade that supports negative-symptom targeting.

This profile focuses on oral ER use and palmitate LAIs (Sustenna, Trinza, Hafyera) for adherence support.

Review cross-titration nuances alongside the Risperidone profile since the agents share metabolic pathways and prolactin considerations.

The compare view and the Paliperidone evidence feed can help contextualize switches and depot escalation planning.

U.S. approvals

Schizophrenia (adults) (2006)
Schizophrenia (adolescents 12–17) (2011)
Schizoaffective disorder (adults) (2009)
Invega Sustenna (monthly LAI) (2009)
Invega Trinza (three-month LAI) (2015)
Invega Hafyera (six-month LAI) (2021)

Formulations & strengths

Paliperidone extended-release (OROS) tablets: 1.5 mg, 3 mg, 6 mg, 9 mg, 12 mg once daily without cyclic titration.
Paliperidone palmitate LAIs: Sustenna (39–234 mg monthly), Trinza (273–819 mg quarterly), Hafyera (1,092–1,560 mg every 6 months); max doses 234 mg, 819 mg, and 1,560 mg per interval.

Generic availability

Generic ER tablets available since 2017; palmitate LAIs remain brand-only.

Steady plasma levels and LAI options make paliperidone central to relapse prevention; prolactin elevation and weight gain require monitoring.

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Paliperidone mechanism of action antagonizes dopamine D2 and serotonin 5-HT2A receptors, mirroring risperidone’s profile with additional α1, α2, and H1 antagonism for negative-symptom coverage.

Minimal muscarinic activity yields low anticholinergic burden.

Antagonist at dopamine D2 receptors.
Antagonist at serotonin 5-HT2A/5-HT2C/5-HT7 receptors.
Antagonist at adrenergic α1/α2 and histamine H1 receptors.
Minimal muscarinic receptor affinity.

Metabolism & pharmacokinetics

Paliperidone pharmacokinetics leverage the OROS extended-release system; once-daily ER tablets reach peak levels ~24 hours post-dose and food increases exposure by ~60%.
Approximately 74% protein bound; volume of distribution ~487 L.
Minimal hepatic metabolism; primarily renally excreted unchanged (~59%).
Oral paliperidone half-life averages ~23 hours, while paliperidone palmitate LAIs exhibit apparent half-lives spanning 25–139 days depending on PP1M/PP3M/PP6M interval.
Eliminated largely in urine with minor fecal excretion.

Dosing & administration

Paliperidone extended-release tablets: start 6 mg once daily; adjust 3–12 mg/day (max 12 mg/day; adolescents start at 3 mg daily).
Schizoaffective disorder: initiate 6 mg once daily; adjust 3–12 mg/day as monotherapy or adjunct (max 12 mg/day).
Renal impairment: reduce starting dose to 3 mg (CrCl 50–79) or 1.5 mg (CrCl 10–49); avoid if CrCl <10.
Invega Sustenna: loading 234 mg (day 1 deltoid) and 156 mg (day 8 deltoid) then 39–234 mg monthly (max 234 mg monthly).
Invega Trinza: eligible after ≥4 months on Sustenna; dose conversion based on last Sustenna dose (e.g., 117 mg → 410 mg quarterly; max 819 mg quarterly).
Invega Hafyera: eligible after stability on Trinza; 1,092 mg or 1,560 mg every 6 months (max 1,560 mg every 6 months).

Long‑acting injectable (LAI) options

Paliperidone palmitate (PP1M/PP3M/PP6M)
Interval
Monthly / q3mo / q6mo
Oral overlap
None after loading sequence
Injection site
Deltoid (initiation) or gluteal
Notes
- PP1M loading: Day 1 deltoid 234 mg, Day 8 deltoid 156 mg
- PP3M/PP6M require stabilization on PP1M/PP3M first
Citations
Label Label Label PMCID

Adverse effects

FDA boxed warnings

Increased mortality in elderly patients with dementia-related psychosis (class warning).

Common side effects (≥10%)

Extrapyramidal symptoms: Akathisia/parkinsonism in ~10–20% depending on dose.
Hyperprolactinemia: Galactorrhea, amenorrhea, gynecomastia in 20–30%.
Weight gain: ≥7% gain in 5–12% of patients.
Tachycardia: Approximately 10% in trials.
Somnolence: Around 10% overall.

Other notable effects

Monitor prolactin-related symptoms and bone health for long-term therapy.
Orthostatic hypotension and syncope due to α1 antagonism, notably during initiation.
QT prolongation modest but warrants caution with other QT-active drugs.
Injection-site reactions generally mild; ensure proper technique and rotation.
Rare cases of neuroleptic malignant syndrome and tardive dyskinesia reported.

Interactions

Strong CYP3A4 or P-gp inducers (carbamazepine, rifampin, St. John’s wort) decrease exposure; avoidance or closer monitoring is often used.
Strong P-gp inhibitors (clarithromycin, verapamil) may increase exposure; monitoring for adverse effects is typical.
Concurrent risperidone elevates paliperidone levels; overlap may require dose adjustment.
Additive CNS depression with alcohol, benzodiazepines, opioids.
May antagonize dopaminergic agents; paliperidone is often avoided in Parkinson’s disease when possible.

Other useful information

Renal function strongly influences dosing; creatinine clearance is typically assessed at baseline and rechecked periodically.
Counseling often covers prolactin-related symptoms and fertility concerns.
Routine metabolic monitoring remains standard despite moderate weight gain risk.
Manufacturer algorithms are typically used, and oral tolerability is commonly confirmed before LAI initiation.
Adherence planning is especially important when transitioning from oral to LAI regimens.
The LAI Navigator can support Sustenna/Trinza/Hafyera planning, alongside the Risperidone profile for cross-titration context and the bipolar disorder hub for schizoaffective mood strategies.

References

Related hubs:Schizophrenia hub·Bipolar hub·LAI hub