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Citation bot (talk | contribs) Add: article-number, volume. | Use this bot. Report bugs. | Suggested by Abductive | Category:World Health Organization essential medicines | #UCB_Category 291/525 |
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{{Short description|Antipsychotic medication}}
{{Use dmy dates|date=February 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 464382756
| image = Risperidone.svg
| image_class = skin-invert-image
| width = 250
| alt =
| image2 = Risperidone3D.png
| width2 = 300
| alt2 = <!-- Clinical data -->
| pronounce =
| tradename = Risperdal, Okedi, others<ref name=generics/>
| Drugs.com = {{drugs.com|monograph|risperidone}}
| MedlinePlus = a694015
| DailyMedID = Risperidone
| pregnancy_AU = C
| routes_of_administration = [[Oral administration|By mouth]], [[intramuscular injection|intramuscular]], [[subcutaneous injection|subcutaneous]]
| class = [[Atypical antipsychotic]]<ref name=AHFS2015/>
| ATC_prefix = N05
| ATC_suffix = AX08
| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Risperdal Product information | website=[[Health Canada]] | date=28 March 2019 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=13904 | access-date=2 April 2024 | archive-date=2 April 2024 | archive-url=https://web.archive.org/web/20240402044135/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=13904 | url-status=live }}</ref>
| legal_UK = POM
| legal_UK_comment = <ref name="Risperdal SmPC">{{cite web | title=Risperdal Consta 25 mg powder and solvent for prolonged-release suspension for injection - Summary of Product Characteristics (SmPC) | website=(emc) | date=6 December 2018 | url=https://www.medicines.org.uk/emc/product/1690/smpc | access-date=29 January 2022 | archive-date=30 January 2022 | archive-url=https://web.archive.org/web/20220130045004/https://www.medicines.org.uk/emc/product/1690/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Risperdal FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Okedi EPAR">{{cite web | title=Okedi EPAR | website=[[European Medicines Agency]] (EMA) | date=15 December 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/okedi | access-date=2 March 2022 | archive-date=3 March 2022 | archive-url=https://web.archive.org/web/20220303055511/https://www.ema.europa.eu/en/medicines/human/EPAR/okedi | url-status=live }}</ref>
<!-- Pharmacokinetic data -->| bioavailability = 70% (by mouth)<ref name=AHFS2015/>
| metabolism = [[Liver]] ([[CYP2D6]] mediated to [[9-hydroxyrisperidone]])<ref name=AHFS2015/>
| elimination_half-life = 20 hours (by mouth), 3–6 days (IM)<ref name=AHFS2015/>
| excretion = Urinary (70%) feces (14%)<ref name=AHFS2015/>
<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 106266-06-2
| PubChem = 5073
| PubChemSubstance = 475100
| IUPHAR_ligand = 96
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00734
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4895
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = L6UH7ZF8HC
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00426
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 8871
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 85
| PDB_ligand = 8NU
| synonyms = <!-- Chemical data -->
| IUPAC_name = 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
| C = 23
| H = 27
| F = 1
| N = 4
| O = 2
| SMILES = Cc1c(c(=O)n2c(n1)CCCC2)CCN3CCC(CC3)c4c5ccc(cc5on4)F
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C23H27FN4O2/c1-15-18(23(29)28-10-3-2-4-21(28)25-15)9-13-27-11-7-16(8-12-27)22-19-6-5-17(24)14-20(19)30-26-22/h5-6,14,16H,2-4,7-13H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RAPZEAPATHNIPO-UHFFFAOYSA-N
}}
[[File:Rispolept Risperidone.jpg|thumb|A box of Rispolept (Risperidone) tablets]]
<!-- Definition and medical uses -->
'''Risperidone''', sold under the brand name '''Risperdal''' among others, is an [[atypical antipsychotic]]<ref name=AHFS2015>{{cite web|title=Risperidone|url=https://www.drugs.com/monograph/risperidone.html|publisher=The American Society of Health-System Pharmacists|access-date=1 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151202010615/http://www.drugs.com/monograph/risperidone.html|archive-date=2 December 2015}}</ref> used to treat [[schizophrenia]] and [[bipolar disorder]],<ref name="AHFS2015" /> as well as aggressive and self-injurious behaviors associated with [[autism spectrum disorder]].<ref name=":0" /> It is taken either [[Oral administration|by mouth]] or by injection (i.e., [[Subcutaneous administration|subcutaneous]] or [[Intramuscular injection|intramuscular]]).<ref name=AHFS2015/> The injectable versions are long-acting and last for 2–4 weeks.<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|pages=434–435}}</ref>
<!-- Side effects -->
Common side effects include [[weight gain]], [[Somnolence|drowsiness]], [[fatigue]], [[insomnia]], [[dry mouth]], [[constipation]], [[Hyperprolactinaemia|elevated prolactin levels]], and [[Akathisia|restlessness]].<ref name=AHFS2015/><ref name=Has2012>{{cite journal | vauthors = Hasnain M, Vieweg WV, Hollett B | title = Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians | journal = Postgraduate Medicine | volume = 124 | issue = 4 | pages = 154–67 | date = July 2012 | pmid = 22913904 | doi = 10.3810/pgm.2012.07.2577 | s2cid = 39697130 }}</ref> Serious side effects may include the potentially permanent movement disorder [[tardive dyskinesia]], as well as [[neuroleptic malignant syndrome]], an increased risk of [[suicide]], and [[hyperglycemia|high blood sugar levels]].<ref name=AHFS2015/><ref name=Ric2015/> In older people with [[psychosis]] as a result of [[dementia]], it may increase the risk of death.<ref name=AHFS2015/> It is unknown if it is safe for use in pregnancy.<ref name=AHFS2015/> Its mechanism of action is not entirely clear, but is believed to be related to its action as a [[dopamine antagonist|dopamine]] and [[serotonin antagonist]].<ref name=AHFS2015/>
<!-- History, society, and culture -->
Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993.<ref name=AHFS2015/><ref name=":0">{{cite book | vauthors = Schatzberg AF, Nemeroff CB |title=The American Psychiatric Publishing textbook of psychopharmacology|date=2009|publisher=American Psychiatric Pub.|___location=Washington, D.C.|isbn=9781585623099|pages = 627|edition=4th|url=https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA627}}</ref><ref name="Risperdal FDA label">{{cite web |title=Risperdal- risperidone tablet Risperdal M-Tab- risperidone tablet, orally disintegrating Risperdal- risperidone solution |url= https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e117c7e-02fc-4343-92a1-230061dfc5e0 |access-date=31 December 2019 |website=DailyMed |archive-date=30 April 2017 |archive-url=https://web.archive.org/web/20170430220000/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e117c7e-02fc-4343-92a1-230061dfc5e0 |url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | ___location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=Ric2015/> In 2023, it was the 176th most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref>{{cite web |title=The Top 300 of 2023 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |url-status=live |archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx |archive-date=12 August 2025 |access-date=13 August 2025 |website=ClinCalc}}</ref><ref>{{cite web |title=Risperidone Drug Usage Statistics, United States, 2014 - 2023 |url=https://clincalc.com/DrugStats/Drugs/Risperidone |access-date=13 August 2025 |website=ClinCalc}}</ref>
==Medical uses==
Risperidone is mainly used for the treatment of [[schizophrenia]], [[bipolar disorder]], and [[irritability]] associated with [[autism]].<ref name=AHFS>{{cite web|title=Respiridone|url=https://www.drugs.com/monograph/risperidone.html|website=The American Society of Health-System Pharmacists|access-date=3 April 2011|url-status=live|archive-url=https://web.archive.org/web/20110413025208/http://www.drugs.com/monograph/risperidone.html|archive-date=13 April 2011}}</ref>
===Schizophrenia===
Risperidone is effective in treating [[Psychogenic disease|psychogenic]] [[polydipsia]] and the acute exacerbations of schizophrenia.<ref name="auto1">{{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 = 951–62 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref><ref>{{cite journal | vauthors = Osser DN, Roudsari MJ, Manschreck T | title = The psychopharmacology algorithm project at the Harvard South Shore Program: an update on schizophrenia | journal = Harvard Review of Psychiatry | volume = 21 | issue = 1 | pages = 18–40 | year = 2013 | pmid = 23656760 | doi = 10.1097/HRP.0b013e31827fd915 | s2cid = 22523977 }}</ref>
Studies evaluating the utility of risperidone by mouth for maintenance therapy have reached varying conclusions. A 2012 systematic review concluded that evidence is strong that risperidone is more effective than all first-generation antipsychotics other than [[haloperidol]], but that evidence directly supporting its superiority to placebo is equivocal.<ref>{{cite journal | vauthors = Barry SJ, Gaughan TM, Hunter R | title = Schizophrenia | journal = BMJ Clinical Evidence | volume = 2012 | date = June 2012 | pmid = 23870705 | pmc = 3385413 }}</ref> A 2011 review concluded that risperidone is more effective in relapse prevention than other first- and second-generation antipsychotics with the exception of [[olanzapine]] and clozapine.<ref>{{cite journal | vauthors = Glick ID, Correll CU, Altamura AC, Marder SR, Csernansky JG, Weiden PJ, Leucht S, Davis JM | title = Mid-term and long-term efficacy and effectiveness of antipsychotic medications for schizophrenia: a data-driven, personalized clinical approach | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 12 | pages = 1616–27 | date = December 2011 | pmid = 22244023 | doi = 10.4088/JCP.11r06927 }}</ref> A 2016 Cochrane review suggests that risperidone reduces the overall symptoms of schizophrenia, but firm conclusions are difficult to make due to very low-quality evidence. Data and information are scarce, poorly reported, and probably biased in favour of risperidone, with about half of the included trials developed by drug companies. The article raises concerns regarding the serious side effects of risperidone, such as parkinsonism.<ref name=Cochrane2016>{{cite journal | vauthors = Rattehalli RD, Zhao S, Li BG, Jayaram MB, Xia J, Sampson S | title = Risperidone versus placebo for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD006918 | date = December 2016 | issue = 12 | pmid = 27977041 | pmc = 6463908 | doi = 10.1002/14651858.CD006918.pub3 | url = http://eprints.whiterose.ac.uk/134704/1/Rattehalli_et_al_2016_Cochrane_Database_of_Systematic_Reviews.pdf | access-date = 27 November 2018 | archive-date = 28 January 2019 | archive-url = https://web.archive.org/web/20190128030405/http://eprints.whiterose.ac.uk/134704/1/Rattehalli_et_al_2016_Cochrane_Database_of_Systematic_Reviews.pdf | url-status = live }}</ref> A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as [[olanzapine]] for schizophrenia:<ref name=Kom2011>{{cite journal | vauthors = Komossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, Leucht S | title = Risperidone versus other atypical antipsychotics for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006626 | date = January 2011 | volume = 2013 | pmid = 21249678 | pmc = 4167865 | doi = 10.1002/14651858.CD006626.pub2 }}</ref>
{| class="wikitable"
! Summary
|-
|Risperidone seems to produce somewhat more [[Extrapyramidal symptoms|extrapyramidal]] side effects and clearly more prolactin increase than other [[atypical antipsychotic]]s. It may also differ from other compounds in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation, and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes drawing firm conclusions difficult.<ref name=Kom2011/>
|-
| style="padding:0;" |
{| class="wikitable collapsible collapsed" style="width:100%;"
|-
! scope="col" style="text-align: left;"| Outcome
! scope="col" style="text-align: left;"| Findings in words
! scope="col" style="text-align: left;"| Findings in numbers
! scope="col" style="text-align: left;"| Quality of evidence
|-
! colspan="4" style="text-align: left;"| Global state
|-
| No clinically significant response || Risperidone is not clearly different when compared to olanzapine. Data supporting this finding are based on moderate-quality evidence.
|| [[Relative risk|RR]] 1.06 (0.99 to 1.13) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
| Leaving the study early due to any reason || Risperidone probably slightly increases the chance of leaving the study early, when compared with olanzapine. Data are based on moderate-quality evidence.
|| RR 1.14 (1.07 to 1.21) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]
|-
! colspan="4" style="text-align: left;"| Service outcome
|-
| Number of patients rehospitalized<br />Follow-up: up to 12 weeks|| No clear difference is seen between risperidone and olanzapine for the outcome of how much hospital/community care is used. These findings are based on data of low quality.
|| RR 1.35 (0.41 to 4.40) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Low]]
|-
! colspan="4" style="text-align: left;"| [[Mental health|Mental state]]
|-
| Average [[Positive and Negative Syndrome Scale]] (PANSS) score (high = poor)<br />Follow-up: up to 12 weeks|| On average, people receiving risperidone scored slightly higher (worse) than people treated with olanzapine but there was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of low quality. || [[Mean absolute difference|MD]] 0.97 higher (1.1 lower to 3.05 higher) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Low]]
|-
! colspan="4" style="text-align: left;"| [[Adverse event|Adverse effects]]
|-
| At least one adverse effect || There was no clear difference between risperidone and olanzapine for this very general adverse effect outcome. These findings are based on data of low quality.
|| RR 0.96 (0.88 to 1.03) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Low]]
|-
! colspan="4" style="text-align: left;"| [[Quality of life]]
|-
| Average QLS scale score (high = poor)<br />Follow-up: over 26 weeks || On average, people receiving risperidone scored higher than people treated with olanzapine. There was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of moderate quality. || [[Mean absolute difference|MD]] 0.97 higher (1.1 lower to 3.05 higher) || Moderate
|-
|}
|}
Long-acting injectable formulations of antipsychotic drugs provide improved compliance with therapy and reduce relapse rates relative to oral formulations.<ref>{{cite journal | vauthors = Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S | title = Oral versus depot antipsychotic drugs for schizophrenia--a critical systematic review and meta-analysis of randomised long-term trials | journal = Schizophrenia Research | volume = 127 | issue = 13 | pages = 83–92 | date = April 2011 | pmid = 21257294 | doi = 10.1016/j.schres.2010.11.020 | s2cid = 2386150 }}</ref><ref>{{cite journal | vauthors = Lafeuille MH, Dean J, Carter V, Duh MS, Fastenau J, Dirani R, Lefebvre P | title = Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia | journal = Current Medical Research and Opinion | volume = 30 | issue = 8 | pages = 1643–55 | date = August 2014 | pmid = 24730586 | doi = 10.1185/03007995.2014.915211 | s2cid = 24814527 }}</ref> The efficacy of risperidone long-acting injection appears to be similar to that of long-acting injectable forms of first-generation antipsychotics.<ref>{{cite journal | vauthors = Nielsen J, Jensen SO, Friis RB, Valentin JB, Correll CU | title = Comparative effectiveness of risperidone long-acting injectable vs first-generation antipsychotic long-acting injectables in schizophrenia: results from a nationwide, retrospective inception cohort study | journal = Schizophrenia Bulletin | volume = 41 | issue = 3 | pages = 627–36 | date = May 2015 | pmid = 25180312 | pmc = 4393684 | doi = 10.1093/schbul/sbu128 }}</ref>
===Bipolar disorder===
Second-generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder.<ref>{{cite journal | vauthors = Muralidharan K, Ali M, Silveira LE, Bond DJ, Fountoulakis KN, Lam RW, Yatham LN | title = Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: a meta-analysis of placebo-controlled trials | journal = Journal of Affective Disorders | volume = 150 | issue = 2 | pages = 408–14 | date = September 2013 | pmid = 23735211 | doi = 10.1016/j.jad.2013.04.032 }}</ref><ref>{{cite journal | vauthors = Nivoli AM, Murru A, Goikolea JM, Crespo JM, Montes JM, González-Pinto A, García-Portilla P, Bobes J, Sáiz-Ruiz J, Vieta E | title = New treatment guidelines for acute bipolar mania: a critical review | journal = Journal of Affective Disorders | volume = 140 | issue = 2 | pages = 125–41 | date = October 2012 | pmid = 22100133 | doi = 10.1016/j.jad.2011.10.015 | hdl = 10651/11126 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Yildiz A, Vieta E, Leucht S, Baldessarini RJ | title = Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials | journal = Neuropsychopharmacology | volume = 36 | issue = 2 | pages = 375–89 | date = January 2011 | pmid = 20980991 | pmc = 3055677 | doi = 10.1038/npp.2010.192 }}</ref> In children and adolescents, risperidone may be more effective than [[lithium (medication)|lithium]] or [[valproate]], but has more metabolic side effects.<ref>{{cite journal | vauthors = Peruzzolo TL, Tramontina S, Rohde LA, Zeni CP | title = Pharmacotherapy of bipolar disorder in children and adolescents: an update | journal = Revista Brasileira de Psiquiatria | volume = 35 | issue = 4 | pages = 393–405 | year = 2013 | pmid = 24402215 | doi = 10.1590/1516-4446-2012-0999 | doi-access = free | hdl = 10183/181642 | hdl-access = free }}</ref> As maintenance therapy, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes.<ref>{{cite journal | vauthors = Gitlin M, Frye MA | title = Maintenance therapies in bipolar disorders | journal = Bipolar Disorders | volume = 14 | issue = Suppl 2 | pages = 51–65 | date = May 2012 | pmid = 22510036 | doi = 10.1111/j.1399-5618.2012.00992.x | s2cid = 21101054 }}</ref> The long-acting injectable form of risperidone may be advantageous over long-acting first-generation antipsychotics, as it is better tolerated (fewer extrapyramidal effects) and because long acting injectable formulations of first-generation antipsychotics may increase the risk of depression.<ref>{{cite journal | vauthors = Gigante AD, Lafer B, Yatham LN | title = Long-acting injectable antipsychotics for the maintenance treatment of bipolar disorder | journal = CNS Drugs | volume = 26 | issue = 5 | pages = 403–20 | date = May 2012 | pmid = 22494448 | doi = 10.2165/11631310-000000000-00000 | s2cid = 2786921 }}</ref>
===Autism===
Compared to [[placebo]], risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, challenging behavior, and rapid mood changes.<ref>{{cite journal | vauthors = Jesner OS, Aref-Adib M, Coren E | title = Risperidone for autism spectrum disorder | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD005040 | date = January 2007 | volume = 2010 | pmid = 17253538 | doi = 10.1002/14651858.CD005040.pub2 | pmc = 9022437 }}</ref> The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments.<ref>{{cite journal | vauthors = Kirino E | title = Efficacy and tolerability of pharmacotherapy options for the treatment of irritability in autistic children | journal = Clinical Medicine Insights. Pediatrics | volume = 8 | pages = 17–30 | year = 2014 | article-number = CMPed.S8304 | pmid = 24932108 | pmc = 4051788 | doi = 10.4137/CMPed.S8304 }}</ref> Weight gain is an important adverse effect.<ref name="Risperdal FDA label" /><ref>{{cite journal | vauthors = Sharma A, Shaw SR | title = Efficacy of risperidone in managing maladaptive behaviors for children with autistic spectrum disorder: a meta-analysis | journal = Journal of Pediatric Health Care | volume = 26 | issue = 4 | pages = 291–9 | year = 2012 | pmid = 22726714 | doi = 10.1016/j.pedhc.2011.02.008 }}</ref> Some authors recommend limiting the use of risperidone and [[aripiprazole]] to those with the most challenging behavioral disturbances to minimize the risk of drug-induced adverse effects.<ref>{{cite journal | vauthors = McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, Veenstra-Vanderweele J | title = A systematic review of medical treatments for children with autism spectrum disorders | journal = Pediatrics | volume = 127 | issue = 5 | pages = e1312–21 | date = May 2011 | pmid = 21464191 | doi = 10.1542/peds.2011-0427 | s2cid = 2903864 }}</ref> Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.<ref>{{cite journal | vauthors = Dove D, Warren Z, McPheeters ML, Taylor JL, Sathe NA, Veenstra-VanderWeele J | title = Medications for adolescents and young adults with autism spectrum disorders: a systematic review | journal = Pediatrics | volume = 130 | issue = 4 | pages = 717–26 | date = October 2012 | pmid = 23008452 | pmc = 4074627 | doi = 10.1542/peds.2012-0683 }}</ref>
===Dementia===
While antipsychotic medications such as risperidone have a slight benefit in people with [[dementia]], they have been linked to a higher incidence of death and stroke.<ref name="pmid22784311" /> Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA-approved and carries a black box warning.<ref name="Risperdal FDA label" /> However, many other jurisdictions regularly use it to control severe aggression and psychosis in those with dementia when other non-pharmacological interventions have failed and their pharmaceutical regulators have approved its use in this population.<ref>{{Cite web |title=Risperidone: Revised PBS restrictions for behavioural and psychological symptoms of dementia |url=https://www.nps.org.au/radar/articles/risperidone-revised-pbs-restrictions-for-behavioural-and-psychological-symptoms-of-dementia |access-date=14 May 2022 |website=NPS MedicineWise |date=19 March 2020 |language=en |archive-date=14 May 2022 |archive-url=https://web.archive.org/web/20220514092650/https://www.nps.org.au/radar/articles/risperidone-revised-pbs-restrictions-for-behavioural-and-psychological-symptoms-of-dementia |url-status=live }}</ref><ref>{{Cite web |title=Antipsychotics and other drug approaches in dementia care {{!}} Alzheimer's Society |url=https://www.alzheimers.org.uk/about-dementia/treatments/drugs/antipsychotic-drugs |access-date=14 May 2022 |website=www.alzheimers.org.uk |date=13 August 2021 |language=en |archive-date=21 January 2022 |archive-url=https://web.archive.org/web/20220121095339/https://www.alzheimers.org.uk/about-dementia/treatments/drugs/antipsychotic-drugs |url-status=live }}</ref>
===Other uses===
Risperidone has demonstrated clinical benefit as an [[Augmentation (pharmacology)|augmentation]] agent in the management of (unipolar) non-psychotic [[treatment-resistant depression]] alongside antidepressant treatment.<ref>{{cite journal |vauthors=Keitner GI, Garlow SJ, Ryan CE, Ninan PT, Solomon DA, Nemeroff CB, Keller MB |title=A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression |journal=J Psychiatr Res |volume=43 |issue=3 |pages=205–14 |date=January 2009 |pmid=18586273 |pmc=3685867 |doi=10.1016/j.jpsychires.2008.05.003 }}</ref> Atypical antipsychotics, such as risperidone, are among the most common augments for antidepressant therapy. Such usage occurs [[Off-label use|off-label]] in most jurisdictions and the risk of adverse effects (e.g., weight gain, movement disorders) must be carefully weighed against the clinical benefit.<ref>{{cite journal |vauthors=Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC |title=Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes |journal=PLOS Med |volume=10 |issue=3 |pages=e1001403 |date=2013 |pmid=23554581 |pmc=3595214 |doi=10.1371/journal.pmed.1001403 |doi-access=free }}</ref>
Risperidone has shown promise in treating therapy-resistant [[obsessive–compulsive disorder]], when [[serotonin reuptake inhibitor]]s alone are not sufficient.<ref name="pmid22932229">{{cite journal | vauthors = Dold M, Aigner M, Lanzenberger R, Kasper S | title = Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 3 | pages = 557–74 | date = April 2013 | pmid = 22932229 | doi = 10.1017/S1461145712000740 | doi-access = free }}</ref>
Risperidone has proven to be effective in treatment of aggression associated with [[attention deficit hyperactivity disorder]] (ADHD),<ref>{{cite journal | vauthors = Eapen V, Gururaj AK | title = Risperidone treatment in 12 children with developmental disorders and attention-deficit/hyperactivity disorder | journal = Primary Care Companion to the Journal of Clinical Psychiatry | volume = 7 | issue = 5 | pages = 221–224 | date = 2005 | pmid = 16308577 | pmc = 1257406 | doi = 10.4088/pcc.v07n0502 }}</ref><ref>{{cite journal | vauthors = Armenteros JL, Lewis JE, Davalos M | title = Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: a placebo-controlled pilot study | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 46 | issue = 5 | pages = 558–565 | date = May 2007 | pmid = 17450046 | doi = 10.1097/chi.0b013e3180323354 }}</ref> or with another mental condition.<ref>{{cite journal | vauthors = Biederman J, Hammerness P, Doyle R, Joshi G, Aleardi M, Mick E | title = Risperidone treatment for ADHD in children and adolescents with bipolar disorder | journal = Neuropsychiatric Disease and Treatment | volume = 4 | issue = 1 | pages = 203–207 | date = February 2008 | pmid = 18728799 | pmc = 2515893 | doi = 10.2147/ndt.s1992 | doi-access = free }}</ref>
Risperidone has not demonstrated a benefit in the treatment of eating disorders or personality disorders, except for limited evidence in [[schizotypal personality disorder]].<ref name="pmid22784311">{{cite journal | vauthors = Maher AR, Theodore G | title = Summary of the comparative effectiveness review on off-label use of atypical antipsychotics | journal = Journal of Managed Care Pharmacy | volume = 18 | issue = 5 Suppl B | pages = S1–20 | date = June 2012 | pmid = 22784311 | doi = 10.18553/jmcp.2012.18.s5-b.1 | pmc = 10438344 | doi-access = free }}</ref>
=== Available forms ===
Available forms of risperidone include [[Tablet (pharmacy)|tablet]], [[orally dissolving tablet]], oral solution, and powder and solvent for injection.<ref>Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com {{Webarchive|url=https://web.archive.org/web/20210610002537/https://www.medicinescomplete.com/ |date=10 June 2021 }} [Accessed on 2 February 2020]</ref>
==Adverse effects==
{{See also|List of adverse effects of risperidone}}
Common side effects include [[extrapyramidal symptoms|movement problems]], [[sedation|sleepiness]], [[dizziness]], trouble seeing, constipation, and increased weight.<ref name=AHFS2015/><ref name=Has2012/> About 9 to 20% of people gained more than 7% of the baseline weight depending on the dose.<ref name=AHFS2015/> Serious side effects may include the potentially permanent movement disorder [[tardive dyskinesia]], as well as [[neuroleptic malignant syndrome]], an increased risk of [[suicide]], and [[hyperglycemia|high blood sugar levels]].<ref name=AHFS2015/><ref name=Ric2015/> In older people with [[psychosis]] as a result of dementia, it may increase the risk of death.<ref name=AHFS2015/>
While atypical antipsychotics appear to have a lower rate of movement problems as compared to typical antipsychotics, risperidone has a high risk of movement problems among the atypicals.<ref name=Div2014>{{cite journal | vauthors = Divac N, Prostran M, Jakovcevski I, Cerovac N | title = Second-generation antipsychotics and extrapyramidal adverse effects | journal = BioMed Research International | volume = 2014 | pages = 656370 | date = 2014 | pmid = 24995318 | pmc = 4065707 | doi = 10.1155/2014/656370 | doi-access = free }}</ref><ref name=Pil2017>{{cite journal | vauthors = Pillay J, Boylan K, Carrey N, Newton A, Vandermeer B, Nuspl M, MacGregor T, Jafri SH, Featherstone R, Hartling L | title = First- and Second-Generation Antipsychotics in Children and Young Adults: Systematic Review Update | journal = Comparative Effectiveness Reviews | issue = 184 | pages = ES–24 | date = March 2017 | pmid = 28749632 | quote = Compared with FGAs, SGAs may decrease the risk for experiencing any extrapyramidal symptom (EPS). FGAs probably cause lower gains in weight and BMI. | id = Report 17-EHC001-EF. Bookshelf ID: NBK442352 }}</ref> Atypical antipsychotics, however, are associated with a greater amount of weight gain and other metabolic side effects.<ref>{{cite journal | vauthors = Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, Beck K, Natesan S, Efthimiou O, Cipriani A, Howes OD | title = Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 7 | issue = 1 | pages = 64–77 | date = January 2020 | pmid = 31860457 | pmc = 7029416 | doi = 10.1016/S2215-0366(19)30416-X }}</ref><ref name=Pil2017/>
===Discontinuation===
The [[British National Formulary]] recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.<ref>{{cite book |editor=BMJ Group |title=British National Formulary |edition=57 |date=March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |___location=United Kingdom |issn=0260-535X |pages = 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.}}</ref>
===Dementia===
Older people with dementia-related psychosis are at a higher risk of death.<ref name="Risperdal FDA label" />
==Interactions==
* [[Carbamazepine]] and other [[enzyme inducer]]s may reduce plasma levels of risperidone.<ref name="Risperdal FDA label" /> If a person is taking both carbamazepine and risperidone, the dose of risperidone will likely need to be increased. The new dose should not be more than twice the patient's original dose.<ref name="Risperdal FDA label" />
* [[CYP2D6]] inhibitors, such as the [[SSRI]] medications fluoxetine and paroxetine, may increase plasma levels of risperidone.<ref name="Risperdal FDA label" />
* Since risperidone can cause [[hypotension]], its use should be monitored closely when a patient is also taking [[Antihypertensive drug|antihypertensive medicines]] to avoid severe low blood pressure.<ref name="Risperdal FDA label" />
* Risperidone and its metabolite [[paliperidone]] are reduced in efficacy by [[P-glycoprotein]] [[Enzyme induction and inhibition|inducers]] such as [[St John's wort]].<ref>{{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 = }}</ref><ref>{{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 }}</ref>
* Risperidone has been found to [[dose dependence|dose-dependently]] [[trip killer|block the effects]] of [[serotonergic psychedelic]]s like [[psilocybin]] and [[lysergic acid diethylamide]] (LSD).<ref name="HalmanKongSarris2024">{{cite journal | vauthors = Halman A, Kong G, Sarris J, Perkins D | title = Drug-drug interactions involving classic psychedelics: A systematic review | journal = J Psychopharmacol | volume = 38 | issue = 1 | pages = 3–18 | date = January 2024 | pmid = 37982394 | pmc = 10851641 | doi = 10.1177/02698811231211219 | url = }}</ref><ref name="VollenweiderVollenweider-ScherpenhuyzenBäbler1998">{{cite journal | vauthors = Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D | title = Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action | journal = NeuroReport | volume = 9 | issue = 17 | pages = 3897–3902 | date = December 1998 | pmid = 9875725 | doi = 10.1097/00001756-199812010-00024 | url = }}</ref>
==Pharmacology==
===Pharmacodynamics===
{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}
{| class="wikitable sortable floatright"
|+ Risperidone<ref>{{cite web |url=http://pdsp.med.unc.edu/pdsp.php |title=PDSP Datatbase | work = National Institute of Mental Health | ___location = ChapelHill (NC) | publisher = University of North Carolina |access-date=16 May 2016 |url-status=dead |archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date=8 November 2013 }}</ref><ref name="BenderParrLivingston2023">{{cite journal | vauthors = Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD | title = 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery | journal = J Med Chem | volume = 66 | issue = 16 | pages = 11027–11039 | date = August 2023 | pmid = 37584406 | pmc = 11073569 | doi = 10.1021/acs.jmedchem.3c01178 | url = }}</ref>
|-
! Site !! K<sub>i</sub> (nM)!!
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 423 || Antagonist
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 14.9 || Antagonist
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 84.6 || Antagonist
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 0.17 || Inverse agonist
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 29–61.9 || Inverse agonist
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 12.0 || Inverse agonist
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || 206 || Antagonist
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 2060 || Antagonist
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 6.60 || Irreversible<br />antagonist<ref name="SmithRahman2006">{{cite journal | vauthors = Smith C, Rahman T, Toohey N, Mazurkiewicz J, Herrick-Davis K, Teitler M | title = Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor | journal = Molecular Pharmacology | volume = 70 | issue = 4 | pages = 1264–70 | date = October 2006 | pmid = 16870886 | doi = 10.1124/mol.106.024612 | s2cid = 1678887 }}</ref>
|-
| [[Alpha-1A adrenergic receptor|α<sub>1A</sub>]] || 5.0 || Antagonist
|-
| [[Alpha-1B adrenergic receptor|α<sub>1B</sub>]] || 9.0 || Antagonist
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 16.5 || Antagonist
|-
| [[Alpha-2B adrenergic receptor|α<sub>2B</sub>]] || 108 || Antagonist
|-
| [[Alpha-2C adrenergic receptor|α<sub>2C</sub>]] || 1.30 || Antagonist
|-
| [[D1 receptor|D<sub>1</sub>]] || 244 || Antagonist
|-
| [[D2 receptor|D<sub>2</sub>]] || 3.57 || Antagonist
|-
| [[D2 receptor|D<sub>2S</sub>]] || 4.73 || Antagonist
|-
| [[D2 receptor|D<sub>2L</sub>]] || 4.16 || Inverse agonist
|-
| [[D3 receptor|D<sub>3</sub>]] || 3.6 || Inverse agonist
|-
| [[D4 receptor|D<sub>4</sub>]] || 4.66 || Antagonist
|-
| [[D5 receptor|D<sub>5</sub>]] || 290 || Antagonist
|-
| [[H1 receptor|H<sub>1</sub>]] || 20.1 || Inverse agonist
|-
| [[H2 receptor|H<sub>2</sub>]] || 120 || Inverse agonist
|-
| {{abbrlink|mACh|Muscarinic acetylcholine receptor}} || 10000+ || Negligible
|}
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of [[Extrapyramidal symptoms|extrapyramidal side effects]] (when given at low doses) that has more pronounced [[serotonin antagonism]] than [[Dopamine antagonist|dopamine antagonism]]. Risperidone contains the [[functional group]]s of [[benzisoxazole]] and [[piperidine]] as part of its molecular structure. Although not a butyrophenone, it was developed with the structures of [[benperidol]] and [[ketanserin]] as a basis. It has actions at several 5-HT ([[serotonin]]) [[Receptor (biochemistry)|receptor]] subtypes. These are 5-HT<sub>2C</sub>, linked to weight gain, and 5-HT<sub>2A</sub>, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with typical antipsychotics.<ref name="GG">Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.</ref>
It has been found that [[D-amino acid oxidase|<small>D</small>-amino acid oxidase]], the enzyme that catalyses the breakdown of <small>D</small>-amino acids (e.g. [[D-alanine|<small>D</small>-alanine]] and [[D-serine|<small>D</small>-serine]] — the neurotransmitters) is inhibited by risperidone.<ref>{{cite journal | vauthors = Abou El-Magd RM, Park HK, Kawazoe T, Iwana S, Ono K, Chung SP, Miyano M, Yorita K, Sakai T, Fukui K | title = The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia | journal = Journal of Psychopharmacology | volume = 24 | issue = 7 | pages = 1055–67 | date = July 2010 | pmid = 19329549 | doi = 10.1177/0269881109102644 | s2cid = 39050369 }}</ref>
Risperidone acts on the following receptors:
[[Dopamine receptor]]s: This drug is an antagonist of the D<sub>1</sub> (D<sub>1</sub>, and D<sub>5</sub>) as well as the D<sub>2</sub> (D<sub>2</sub>, D<sub>3</sub> and D<sub>4</sub>) family receptors, with 70-fold selectivity for the D<sub>2</sub> family. It has "tight binding" properties, which means it has a long half-life. Like other antipsychotics, risperidone blocks the mesolimbic pathway, the prefrontal cortex limbic pathway, and the tuberoinfundibular pathway in the central nervous system. Risperidone may induce extrapyramidal side effects, [[akathisia]] and [[tremor]]s, which is associated with diminished dopaminergic activity in the [[striatum]]. It can also cause sexual side effects, [[galactorrhoea]], infertility, [[gynecomastia]], and, with chronic use, reduced bone mineral density leading to [[Bone fracture|breaks]], all of which are associated with increased prolactin secretion.<ref name = "GG" />
[[Alpha-1 adrenergic receptor|Alpha α<sub>1</sub> adrenergic receptors]]: This action accounts for the orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.<ref name = "GG" />
[[Alpha-2 Adrenergic receptor|Alpha α<sub>2</sub> adrenergic receptors]]: Risperidone's action at these receptors may cause greater positive, negative, affective, and cognitive symptom control.<ref>{{cite journal | vauthors = Hecht EM, Landy DC | title = Alpha-2 receptor antagonist add-on therapy in the treatment of schizophrenia; a meta-analysis | journal = Schizophrenia Research | volume = 134 | issue = 2–3 | pages = 202–6 | date = February 2012 | pmid = 22169246 | doi = 10.1016/j.schres.2011.11.030 | s2cid = 36119981 }}</ref>
[[Histamine H1 receptor|Histamine H<sub>1</sub> receptors]]: effects on these receptors account for its sedation and reduction in vigilance. This may also lead to drowsiness and weight gain.<ref name = "GG" />
[[Sodium channel#Voltage-gated sodium channels|Voltage-gated sodium channels]]: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels at clinically used concentrations.<ref>{{cite journal | vauthors = Brauner JM, Hessler S, Groemer TW, Alzheimer C, Huth T | title = Risperidone inhibits voltage-gated sodium channels | journal = European Journal of Pharmacology | volume = 728 | pages = 100–106 | date = April 2014 | pmid = 24508524 | doi = 10.1016/j.ejphar.2014.01.062 }}</ref>
===Pharmacokinetics===
Risperidone undergoes hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe liver and kidney disease.<ref name="Risperdal FDA label" /> The [[active metabolite]] of risperidone, [[paliperidone]], is also used as an antipsychotic.<ref>{{cite web|url=http://www.drugbank.ca/drugs/DB01267|title=The DrugBank database|url-status=live|archive-url=https://web.archive.org/web/20111117205610/http://www.drugbank.ca/drugs/DB01267|archive-date=17 November 2011}}</ref>{{Unreliable medical source|date=July 2023}}
{{Pharmacokinetics of long-acting injectable antipsychotics}}[[File:Risperdal tablets.jpg|thumb|Risperdal (risperidone) 4 mg tablets ([[United Kingdom|UK]])]]
== Society and culture ==
=== Legal status ===
Risperidone was approved by the United States [[Food and Drug Administration]] (FDA) in 1993 for the treatment of schizophrenia.<ref>{{cite web| title =Electronic Orange Book| publisher =Food and Drug Administration| date =April 2007| url =http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020272&TABLE1=OB_Rx| access-date =24 May 2007| url-status =dead| archive-url =https://web.archive.org/web/20070819042519/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020272&TABLE1=OB_Rx| archive-date =19 August 2007}}</ref> In 2003, the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006, the FDA approved risperidone for the treatment of irritability in autistic children and adolescents.<ref>{{cite press release |publisher=FDA |date=6 October 2006 |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108759.htm |title=FDA approves the first drug to treat irritability associated with autism, Risperdal |access-date=14 August 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090828023642/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108759.htm |archive-date=28 August 2009 }}</ref> The FDA's decision was based in part on a study of autistic people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern.<ref>{{cite journal | vauthors = Scahill L | title = How do I decide whether or not to use medication for my child with autism? Should I try behavior therapy first? | journal = Journal of Autism and Developmental Disorders | volume = 38 | issue = 6 | pages = 1197–8 | date = July 2008 | pmid = 18463973 | doi = 10.1007/s10803-008-0573-7 | s2cid = 20767044 }}</ref> On 22 August 2007, risperidone was approved as the only drug agent available for the treatment of schizophrenia in youths, ages 13–17; it was also approved that same day for the treatment of bipolar disorder in youths, ages 10–17, joining [[lithium pharmacology|lithium]].
On 16 December 2021, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) formally recommended market authorization for Okedi, a long-acting [[depot injection]] of risperidone. Okedi was approved for the treatment of schizophrenia in adults for whom the tolerability and effectiveness of risperidone had already been established using an oral formulation.<ref name="Okedi: Pending EC decision">{{cite web | title=Okedi: Pending EC decision | website=European Medicines Agency | date=15 December 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/okedi | access-date=18 December 2021 | archive-date=17 December 2021 | archive-url=https://web.archive.org/web/20211217113416/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/okedi | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Long-acting depot injectable risperidone was approved for medical use in the European Union in February 2022.<ref name="Okedi EPAR" /><ref>{{cite web | title=Okedi Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1621.htm | access-date=3 March 2023 | archive-date=4 March 2023 | archive-url=https://web.archive.org/web/20230304091406/https://ec.europa.eu/health/documents/community-register/html/h1621.htm | url-status=live }}</ref>
=== Lawsuits ===
In April 2012, [[Johnson & Johnson]] (J&J) and its [[subsidiary]] [[Janssen Pharmaceutica|Janssen Pharmaceuticals Inc.]] were fined $1.2 billion for downplaying multiple risks associated with risperidone.<ref>{{cite web | vauthors = Muskal M | title=Companies belittled risks of Risperdal, slapped with huge fine | website=Los Angeles Times | date=11 April 2012 | url=https://www.latimes.com/nation/la-xpm-2012-apr-11-la-na-nn-risperdal-arkansas-20120411-story.html | access-date=15 July 2023 | url-status=live | archive-url=https://web.archive.org/web/20120412005624/http://www.latimes.com/news/nation/nationnow/la-na-nn-risperdal-arkansas-20120411,0,3974735.story | archive-date=12 April 2012 }}</ref> The verdict was later reversed by the Arkansas state supreme court.<ref>{{cite news|url=https://www.nytimes.com/2014/03/21/business/arkansas-court-reverses-1-2-billion-judgment-against-johnson-johnson.html |title=Arkansas Court Reverses $1.2 Billion Judgment Against Johnson & Johnson |url-status=live|archive-url=https://web.archive.org/web/20151105132203/http://www.nytimes.com/2014/03/21/business/arkansas-court-reverses-1-2-billion-judgment-against-johnson-johnson.html |archive-date=5 November 2015|newspaper=[[The New York Times]]|date=20 March 2014| vauthors = Thomas K }}</ref>
In August 2012, J&J agreed to pay $181 million to 36 US states to settle claims that it had promoted risperidone and [[paliperidone]] for [[off-label use]]s including for [[dementia]], [[anger management]], and [[Anxiety disorder|anxiety]].<ref>{{cite news|title=NY AG: Janssen pays $181M over drug marketing|date=30 August 2012|newspaper=The Seattle Times|url=http://www.seattletimes.com/seattle-news/ny-ag-janssen-pays-181m-over-drug-marketing/|url-status=live|archive-url=https://web.archive.org/web/20160407105814/http://www.seattletimes.com/seattle-news/ny-ag-janssen-pays-181m-over-drug-marketing/|archive-date=7 April 2016}}</ref>
In November 2013, J&J was fined $2.2 billion for illegally marketing risperidone for use in people with dementia and paying [[Kickback (bribery)|kickbacks]] to prescribing physicians and nursing home pharmacies.<ref>{{cite press release |url=https://www.justice.gov/opa/pr/johnson-johnson-pay-more-22-billion-resolve-criminal-and-civil-investigations|title=Johnson & Johnson to Pay More Than $2.2 Billion to Resolve Criminal and Civil Investigations|publisher=Department of Justice, Office of Public Affairs|date=4 November 2013|url-status=live|archive-url=https://web.archive.org/web/20150305025106/http://www.justice.gov/opa/pr/johnson-johnson-pay-more-22-billion-resolve-criminal-and-civil-investigations|archive-date=5 March 2015|access-date=23 December 2020}}</ref>
In 2015, [[Steven Brill (journalist)|Steven Brill]] wrote an investigative journalism piece about J&J in ''[[The Huffington Post]]'' focused on J&J's marketing of risperidone.<ref>{{cite news| vauthors = Ashbrook T |title=Johnson & Johnson And The Big Lies Of Big Pharma |url= https://www.wbur.org/onpoint/2015/09/22/big-pharma-risperdal-steven-brill|work=[[On Point]]|date=22 September 2015|url-status=live|archive-url= https://web.archive.org/web/20161122224110/https://www.wbur.org/onpoint/2015/09/22/big-pharma-risperdal-steven-brill |archive-date=22 November 2016}}</ref><ref>{{cite news| vauthors = Brill S |title=America's Most Admired Lawbreaker|url=https://highline.huffingtonpost.com/miracleindustry/americas-most-admired-lawbreaker/ |work=[[The Huffington Post]]|date=September 2015|url-status=live|archive-url=https://web.archive.org/web/20151002123107/http://highline.huffingtonpost.com/miracleindustry/americas-most-admired-lawbreaker/|archive-date=2 October 2015}}</ref>
J&J has faced numerous civil lawsuits on behalf of children who were prescribed risperidone who grew breasts (a condition called [[gynecomastia]]); as of July 2016 there were about 1,500 cases in Pennsylvania state court in Philadelphia, and there had been a February 2015 verdict against J&J with $2.5 million awarded to a man from Alabama, a $1.75 million verdict against J&J that November, and in 2016 a $70 million verdict against J&J.<ref>{{cite news| vauthors = Feeley J |title=J&J Hit With $70 Million Risperdal Verdict Over Male Breasts|url=https://www.bloomberg.com/news/articles/2016-07-01/j-j-faces-record-70-million-verdict-over-male-breasts|work=Bloomberg News|date=1 July 2016|url-status=live|archive-url=https://web.archive.org/web/20170507080914/https://www.bloomberg.com/news/articles/2016-07-01/j-j-faces-record-70-million-verdict-over-male-breasts|archive-date=7 May 2017}}</ref> In October 2019, a jury ordered J&J to pay $8 billion in punitive damages to a Pennsylvania man who had grown breasts during adolescence.<ref name="Murray-8B-verdict">{{cite news |url=https://www.reuters.com/article/us-johnson-johnson-risperdal-verdict/jury-says-jj-must-pay-8-billion-in-case-over-male-breast-growth-linked-to-risperdal-idUSKBN1WN2HK |title=Jury says J&J must pay $8 billion in case over male breast growth linked to Risperdal |date=9 October 2019 |publisher=Reuters |access-date=9 October 2019 |archive-date=9 October 2019 |archive-url=https://web.archive.org/web/20191009220338/https://www.reuters.com/article/us-johnson-johnson-risperdal-verdict/jury-says-jj-must-pay-8-billion-in-case-over-male-breast-growth-linked-to-risperdal-idUSKBN1WN2HK |url-status=live }}</ref> This verdict amount chosen by the jury was reduced more than 1,000-fold by a judge in January 2020, with the new punitive damages being $6.8 million.<ref name="Murray-6.8m-verdict">{{cite news | vauthors = Stempel J |title=Judge slashes $8 billion Risperdal award against Johnson & Johnson to $6.8 million |url=https://www.reuters.com/article/idUSKBN1ZG292/ |access-date=20 May 2024 |work=Reuters |date=2020-01-17}}</ref> A legal scholar commented that [[punitive damages]] which exceed the [[compensatory damages]] by a factor of 10 or more in cases of this type are usually found to be legally invalid.<ref name="Murray-8B-verdict" />
=== Brand names ===
Janssen's patent on risperidone expired in December 2003, opening the market for cheaper [[Generic drug|generic versions]] from other companies, and Janssen's exclusive marketing rights expired in June 2004 (the result of a pediatric extension). It is available under many brand names worldwide.<ref name=generics>Drugs.com [https://www.drugs.com/international/risperidone.html International trade names for risperidone] {{webarchive|url=https://web.archive.org/web/20160318043334/http://www.drugs.com/international/risperidone.html |date=18 March 2016 }} Page accessed 15 March 2016</ref>
Risperidone is available as a tablet, an oral solution, and an ampule, which is a [[depot injection]].<ref name=generics/>
Brand names include Risperdal, Risperdal Consta, Risperdal M-Tab, Risperdal Quicklets, Risperlet, Okedi, and Perseris.<ref>{{Cite web|title=Risperidone: MedlinePlus Drug Information|url=https://medlineplus.gov/druginfo/meds/a694015.html|access-date=28 September 2020|website=medlineplus.gov|archive-date=25 September 2020|archive-url=https://web.archive.org/web/20200925101710/https://medlineplus.gov/druginfo/meds/a694015.html|url-status=live}}</ref>
==References==
{{Reflist}}
==Further reading==
* {{cite book | title=Medical Genetics Summaries | chapter=Risperidone Therapy and CYP2D6 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK425795/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2017 | pmid=28520384 | id=Bookshelf ID: NBK425795 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
==External links==
{{commons category-inline|Risperidone}}
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