Paliperidone

Overview

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic. It is used for the treatment of schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals.[1][2][3] WP

Paliperidone was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in December 2006, and in the European Union in June 2007. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester. It is on the World Health Organization's List of Essential Medicines. Paliperidone is available as a generic medication.[1][3–7] WP

Uses, dosage and effects

Medical use

In the United States, paliperidone is indicated for the treatment of schizophrenia and for the treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants.[2][3] WP

In the European Union, paliperidone is indicated for the treatment of schizophrenia in adults and in adolescents fifteen years of age and older and for the treatment of schizoaffective disorder in adults.[4] WP

Risks and side effects

Adverse effects

The most common side effects include headache, insomnia, sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, weight gain, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough.[4] WP

A 2020 pharmacovigilance study using the Korean Adverse Event Reporting System (KAERS) compared safety signals for paliperidone with those of other atypical antipsychotics. The analysis found that paliperidone was disproportionately associated with hyperprolactinemia‑related events (galactorrhea, amenorrhea, gynecomastia), weight increase, and metabolic disturbances. The authors concluded that the real‑world safety profile of paliperidone warrants continued monitoring, particularly for endocrine and metabolic adverse effects.[8] WP

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo in the early months of psychosis treatment.[9] WP

Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[10] WP

Pharmacology

Pharmacology

Paliperidone is the primary active metabolite of the older antipsychotic risperidone. While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways. Its efficacy is believed to result from central dopaminergic and serotonergic antagonism except paliperidone, like its parent compound risperidone, functions as an inverse agonist at 5-HT2A receptor 15. Paliperidone also acts as an antagonist of alpha-1 and alpha-2 adrenergic receptors as well as H₁ histamine receptors. Food is known to increase the absorption of Invega type ER OROS prolonged-release tablets. Food increased exposure of paliperidone by up to 50-60%; however, half-life was not significantly affected. The effect was probably due to a delay in the transit of the ER OROS formulation in the upper part of the GI tract, resulting in increased absorption.[11][12][13] WP

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[14][15] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Values are Kᵢ (nM). The smaller the value, the more strongly the drug binds to the site. WP

History

History

Paliperidone (as Invega) was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in 2006. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. The long-acting injectable form of paliperidone, marketed as Invega Sustenna in the US, and Xeplion in the EU, was approved by the FDA in July 2009.[16][17] WP

It was initially approved in the European Union in 2007, for schizophrenia, the extended release form and use for schizoaffective disorder were approved in the EU in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.[18] WP

Legal status

Deaths

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone palmitate had died, out of 10,700 individuals prescribed the drug.[19–25] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

On December 4, 2014, a 5-year-old Spanish boy, Borja Piriz Matía, died 15 days after he started taking paliperidone (Invega) 3 mg.[26] WP

In 2019, it was reported that a 33-year-old man died after a single injection of 819 mg of Trevicta (paliperidone palmitate three-monthly injection), with paliperidone poisoning appearing to be the highly likely cause of death.[27] WP

Suicides

On January 17, 2020, a video titled "Medical Help" was uploaded to YouTube by 26-year-old Wail Ardab of Palatka, Florida, who developed dystonia and insomnia after taking Invega Trinza injections. On March 5, 2020, Ardab committed suicide by jumping from Memorial Bridge in Palatka.[28][29] WP

From June 2023 to April 2024, Serbian television presenter and journalist Bojana Nikolić Janković posted to the internet forum Bluelight that she received 4 shots of Invega Sustenna and 2 shots of Invega Trinza due to the stress of her divorce from Ognjen Janković, a member of the hip-hop group Beogradski Sindikat. Janković, known for hosting the show City, wrote that she was bedridden with persistent anhedonia, cognitive issues, low energy and other symptoms consistent with neuroleptic-induced deficit syndrome after receiving the injections. She died in Belgrade on April 19, 2024, at age 46.[30][31][32] WP

Homicides

On December 28, 2021, 19-year-old Peyton Moyer fatally shot his mother and her boyfriend in Watkinsville, Georgia, while under the influence of the long-acting injectable paliperidone palmitate (Invega Sustenna). On November 2, 2023, Moyer was sentenced to life in prison.[33][34] WP

Lawsuits

From 2019 to 2024, Maria Francesca Gioia, a former medical student acting as a pro se plaintiff, filed nine product liability lawsuits against Janssen Pharmaceuticals and related parties. She alleged that taking Invega Sustenna (paliperidone palmitate) caused her memory loss, hypothyroidism, Horner's syndrome, nerve damage, motor tremors, vocal tics, confusion, loss of taste and sensation, post-traumatic stress disorder, and metabolic syndrome (including hypertension, diabetes, and stroke), which ended her career as a primary care physician. All nine lawsuits were dismissed on procedural grounds: Gioia I–II for failure to state a claim, Gioia III for failure to prosecute, and Gioia IV–V for lack of subject matter jurisdiction. The court also noted that the side effects she alleged were already listed on Invega's FDA-approved warning label.[35][36] WP

In September 2024, Cassandra Fameux filed a criminal complaint alleging that her husband, a Michigan anesthesiologist, had forcibly injected her with unprescribed Invega Sustenna on multiple occasions between 2017 and 2021. A subsequent police investigation led to a recommendation that he be charged with domestic assault.[37] WP

In May and June 2022, Adilah Patton, a 28‑year‑old pretrial detainee in Indianapolis, was forcibly injected twice with unprescribed Invega Sustenna while in custody at the Marion County Adult Detention Center. A federal lawsuit filed on her behalf alleges that the injections were administered without a medical assessment, a prescription, or the consent of her court‑appointed guardian. The lawsuit describes the injections as assault, battery, excessive force, and violations of the Fourteenth Amendment right to informed consent.[38][39] WP

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the US Food and Drug Administration under the brand name Invega Trinza. A similar prolonged release suspension was approved in 2016 by the European Medicines Agency originally under the brand name Paliperidone Janssen, later renamed to Trevicta. In September 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.[40–43] WP

Chemistry

Formula

C23H27FN4O3 PC

CAS number

144598-75-4 PC

Molar mass (g/mol)

426.5 PC

IUPAC name (computed by PubChem)

3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one PC

SMILES

CC1=C(C(=O)N2CCCC(C2=N1)O)CCN3CCC(CC3)C4=NOC5=C4C=CC(=C5)F PC

InChIKey

PMXMIIMHBWHSKN-UHFFFAOYSA-N PC

PubChem CID

115237

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Chue P, Chue J. A review of paliperidone palmitate. Expert Review of Neurotherapeutics. December 2012. doi:10.1586/ern.12.137 · PMID 23237346
2. Journal / agency Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. September 2013. doi:10.1016/S0140-6736(13)60733-3 · PMID 23810019
3. Journal / agency Invega- paliperidone tablet, extended release
4. Journal / agency Invega EPAR. June 25, 2007
5. Journal / agency Edinoff AN, Doppalapudi PK, Orellana C, Ochoa C, Patti S, Ghaffar Y, Cornett EM, Kaye AJ, Viswanath O, Urits I, Kaye AM, Kaye AD. Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review. Frontiers in Psychiatry. 2021. doi:10.3389/fpsyt.2021.699748 · PMID 34621193 · PMC8490677
6. Other The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
7. Journal / agency Niapelf EPAR. March 21, 2024
8. Journal / agency Seo DE, Kim S, Park BJ. Signals of adverse drug reactions of paliperidone compared to other atypical antipsychotics using the Korean Adverse Event Reporting System database. Clin Drug Investig. 2020. doi:10.1007/s40261-020-00945-z
9. Journal / agency Allott K, Yuen HP, Baldwin L, O'Donoghue B, Fornito A, Chopra S, Nelson B, Graham J, Kerr MJ, Proffitt TM, Ratheesh A, Alvarez-Jimenez M, Harrigan S, Brown E, Thompson AD, Pantelis C, Berk M, McGorry PD, Francey SM, Wood SJ. Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial. Translational Psychiatry. June 2023. doi:10.1038/s41398-023-02501-7 · PMID 37301832 · PMC10257667
10. Other Haddad PM, Dursun S, Deakin B. Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. 2004
11. Harm reduction site Paliperidone
12. Journal / agency Corena-McLeod M. Comparative Pharmacology of Risperidone and Paliperidone. Drugs in R&D. June 2015. doi:10.1007/s40268-015-0092-x · PMID 25943458 · PMC4488186
13. Journal / agency Paliperidone extended release: Scientific Discussion. July 16, 2007
14. Journal / agency Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL. The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. The International Journal of Neuropsychopharmacology. December 2004. doi:10.1017/S1461145704004390 · PMID 15683552
15. Journal / agency Gurley BJ, Swain A, Williams DK, Barone G, Battu SK. Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Molecular Nutrition & Food Research. July 2008. doi:10.1002/mnfr.200700081 · PMID 18214850 · PMC2562898
16. Journal / agency Invega Sustenna- paliperidone palmitate injection. January 31, 2019
17. Journal / agency Xeplion EPAR. March 4, 2011
18. Journal / agency Procedural steps taken and scientific information after the authorisation. July 16, 2015
19. Other 21 users of schizophrenia drug dead. April 18, 2014
20. Other Schizophrénie: controverse autour d'un médicament au Japon. April 9, 2014
21. Other 20 minutes - Un médicament anti-schizophrénie tue. April 9, 2014
22. Other Deaths reported after Xeplion injections
23. Other 17 deaths reported after schizophrenia drug injections. April 10, 2014
24. Other 21 Dead in Japan From New Johnson & Johnson Antipsychotic. April 18, 2014
25. Other Schizophrenia drug blamed for 17 deaths. June 29, 2023
26. Other Jara M. Habrá juicio penal por la muerte del niño Borja, intoxicado por el fármaco psiquiátrico Invega. February 18, 2021
27. Journal / agency Drevin G, Ripault B. Death following an intramuscular injection of paliperidone: A case report. Toxicologie Analytique et Clinique. November 2019. doi:10.1016/j.toxac.2019.10.006
28. Other Ardab W. Medical Help. January 17, 2020
29. Other Dive team recovers body from river. March 6, 2020
30. Harm reduction site bojana, post to "Coming off Invega/Xeplion (paliperidone) injections v 8.0," Bluelight, December 24, 2023, "So im 10 months off. I have some emotions, i can cry, lost weight, listen to some music. My main problem is 0 motivation, low energy and anhedonia. Also i have cognitive issues. Beddriden mostly.. When do you think it will go away? Im loosing hope
31. Harm reduction site bojana, post to "Coming off Invega/Xeplion (paliperidone) injections v 8.0," Bluelight, March 3, 2024, "They really killed everything in me and about me, im different person who suffers enormasly every day. I juste believed medical doctros and their knowledge. […] I dont accept undignefied life, i was mother, jurnalist, tv host, happiest women ever who adored life, kids, family, friends. Everything is gone. Everything. Somehow deep in my heart i have small hope of being my self again, its just that i am tiered and i had way to much suffering. Life is not worth living anymore, and i cant allowe everybody around me to suffer with me. Id rather be dead, than be this person who i have become
32. Other DECU POSLALA IZ KUĆE, PA OTIŠLA U SMRT! Isplivali novi detalji o Bojani Nikolić! Ugovarala jednu stvar sa sestrom, žalila se NA OVE SIMPTOME!. April 22, 2024
33. Other Robertson R. Doomed by Design: How a Dangerous Drug, a Broken System, and a Failing DA Failed A Mentally Ill Teen. March 27, 2025
34. Other Ford W. Watkinsville man sentenced to life in prison for killing parents in 2021. November 2, 2023
35. Other https://www.courtlistener.com/opinion/9839047/gioia-v-janssen-pharmaceuticals/. February 16, 2021
36. Other https://www.courtlistener.com/opinion/9845094/gioia-v-patterson-belknap-webb-tyler/. April 19, 2024
37. Other Allimadi, Milton. From Hotel Lobby To Psychiatric Ward: The Troubling Ordeal Of Cassandra Fameux. 7 March 2026
38. Other Lawsuit alleges mentally ill woman received forced injections while detained by Marion County authorities. 2024-06-11
39. Other Marion County sheriff, Wellpath accused of forced drug injections on mentally ill inmate. 2024-06-11
40. Journal / agency Invega Trinza (paliperidone palmitate) NDA approval letter
41. Journal / agency Invega Trinza- paliperidone palmitate injection, suspension, extended release. January 31, 2019
42. Journal / agency Trevicta (previously Paliperidone Janssen). September 17, 2018
43. Journal / agency Invega Hafyera- paliperidone palmitate injection, suspension, extended release

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