paliperidone

In the US, 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.

In the EU, 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.

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.{{cite journal | vauthors = 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 | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}

The most frequent 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, increased weight, 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. Palperidone can also rarely cause priapism or sexual dysfunction related to hyperprolactinemia.

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo in the early months of psychosis treatment.{{cite journal | vauthors = 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 | title = 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 | journal = Translational Psychiatry | volume = 13 | issue = 1 | pages = 199 | date = June 2023 | pmid = 37301832 | pmc = 10257667 | doi = 10.1038/s41398-023-02501-7 }}

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.{{cite book | editor = BMJ Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}} Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.{{cite book |vauthors=Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |access-date=August 28, 2020 |archive-date=January 10, 2023 |archive-url=https://web.archive.org/web/20230110164012/https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |url-status=live }} 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. Symptoms generally resolve after a short period of time.

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.{{cite news | url = http://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY | title = 21 users of schizophrenia drug dead | publisher = The Japan Times | newspaper = The Japan Times Online | date = April 18, 2014 | access-date = April 21, 2014 | archive-date = July 3, 2021 | archive-url = https://web.archive.org/web/20210703152415/https://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY | url-status = live }}{{cite news | url = http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php | title = Schizophrénie: controverse autour d'un médicament au Japon | work = Médecine | date = April 9, 2014 | access-date = April 21, 2014 | archive-date = April 22, 2014 | archive-url = https://web.archive.org/web/20140422232448/http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php | url-status = live }}{{cite web | url = http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540 | title = 20 minutes - Un médicament anti-schizophrénie tue | work = Monde | date = April 9, 2014 | access-date = April 21, 2014 | archive-date = April 23, 2014 | archive-url = https://web.archive.org/web/20140423051757/http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540 | url-status = live }}{{cite web | url = http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899 | title = Deaths reported after Xeplion injections | work = Life & Style | publisher = NZ Herald News | access-date = April 21, 2014 | archive-date = March 4, 2016 | archive-url = https://web.archive.org/web/20160304003317/http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899 | url-status = dead }}{{cite web | url = http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections | title = 17 deaths reported after schizophrenia drug injections | work = Japan Today: Japan News and Discussion | date = April 10, 2014 | access-date = April 21, 2014 | archive-date = April 23, 2014 | archive-url = https://web.archive.org/web/20140423055204/http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections | url-status = live }}{{cite web | url = https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/ | title = 21 Dead in Japan From New Johnson & Johnson Antipsychotic | work = Mad In America | date = April 18, 2014 | access-date = April 21, 2014 | archive-date = April 22, 2014 | archive-url = https://web.archive.org/web/20140422232117/https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/ | url-status = live }}{{cite web | url = http://www.skynews.com.au/health/article.aspx?id=966055 | title = Schizophrenia drug blamed for 17 deaths | work = Sky News Australia | date = June 29, 2023 | access-date = April 21, 2014 | archive-date = April 13, 2014 | archive-url = https://web.archive.org/web/20140413192428/http://www.skynews.com.au/health/article.aspx?id=966055 | url-status = live }}{{Excessive citations inline|date=December 2024}}

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.{{cite web | url = http://www.drugbank.ca/drugs/DB01267 | title = Paliperidone | work = DrugBank | access-date = November 18, 2011 | archive-date = November 17, 2011 | archive-url = https://web.archive.org/web/20111117205610/http://www.drugbank.ca/drugs/DB01267 | url-status = live }}{{Unreliable medical source|date=February 2024}} While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.{{cite journal | vauthors = Corena-McLeod M | title = Comparative Pharmacology of Risperidone and Paliperidone | journal = Drugs in R&D | volume = 15 | issue = 2 | pages = 163–174 | date = June 2015 | pmid = 25943458 | pmc = 4488186 | doi = 10.1007/s40268-015-0092-x }} 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 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791992/ 15]. Paliperidone also acts as an antagonist of alpha-1 and alpha-2 adrenergic receptors as well as H1 histaminergic 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.{{cite web | title = Paliperidone extended release: Scientific Discussion | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf | publisher = EMA | date = July 16, 2007 | access-date = May 8, 2017 | archive-date = May 19, 2012 | archive-url = https://web.archive.org/web/20120519124924/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf | url-status = dead }}

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort{{cite journal | vauthors = Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL | title = The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein | journal = The International Journal of Neuropsychopharmacology | volume = 7 | issue = 4 | pages = 415–419 | date = December 2004 | pmid = 15683552 | doi = 10.1017/S1461145704004390 | doi-access = }}{{cite journal | vauthors = Gurley BJ, Swain A, Williams DK, Barone G, Battu SK | title = 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 | journal = Molecular Nutrition & Food Research | volume = 52 | issue = 7 | pages = 772–779 | date = July 2008 | pmid = 18214850 | pmc = 2562898 | doi = 10.1002/mnfr.200700081 }}

{{Pharmacokinetics of long-acting injectable antipsychotics}}

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

Paliperidone (as Invega) was approved by the 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,{{cite web | title=Invega Sustenna- paliperidone palmitate injection | website=DailyMed | date=January 31, 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554 | access-date=August 19, 2020 | archive-date=May 13, 2021 | archive-url=https://web.archive.org/web/20210513225814/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554 | url-status=live }} and Xeplion in the EU, was approved by the FDA in July 2009.

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.{{cite web | title = Procedural steps taken and scientific information after the authorisation | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000746/WC500034930.pdf | publisher = EMA | date = July 16, 2015 | access-date = May 8, 2017 | archive-date = June 18, 2018 | archive-url = https://web.archive.org/web/20180618050405/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000746/WC500034930.pdf | url-status = dead }}

In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.{{cite web | title = Invega Trinza (paliperidone palmitate) NDA approval letter | url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf | website = U.S. Food and Drug Administration | access-date = December 10, 2015 | archive-date = December 22, 2015 | archive-url = https://web.archive.org/web/20151222170554/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf | url-status = live }}{{cite web | title=Invega Trinza- paliperidone palmitate injection, suspension, extended release | website=DailyMed | date=January 31, 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae | access-date=August 19, 2020 | archive-date=June 17, 2021 | archive-url=https://web.archive.org/web/20210617113151/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae | url-status=live }} 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.{{cite web | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004066/human_med_001829.jsp&mid=WC0b01ac058001d124 | title = Trevicta (previously Paliperidone Janssen) | work = Summary of the European public assessment report (EPAR) for Trevicta | publisher = EMC | date = September 17, 2018 | access-date = January 17, 2017 | archive-date = June 20, 2018 | archive-url = https://web.archive.org/web/20180620172955/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F004066%2Fhuman_med_001829.jsp&mid=WC0b01ac058001d124 | url-status = dead }} On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.{{cite web | title=Invega Hafyera- paliperidone palmitate injection, suspension, extended release | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b | access-date=October 31, 2021 | archive-date=October 20, 2021 | archive-url=https://web.archive.org/web/20211020045452/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b | url-status=live }}

{{reflist}}

• {{cite web | title=Paliperidone Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a615032.html }}

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