Aripiprazole

{{Short description|Atypical antipsychotic medication}} {{Use dmy dates|date=November 2025}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 443398218 | image = Aripiprazole chemical structure.svg | image_class = skin-invert-image | alt = Structural formula of aripiprazole | width = 250px | image2 = Aripiprazole molecule from xtal ball.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the aripiprazole molecule | width2 = 250px | caption =  | pronounce = {{IPAc-en|ˌ|æ|r|ᵻ|ˈ|p|ɪ|p|r|ə|z|oʊ|l}} {{respell|AIR|ih|PIP|rə|zohl}} Abilify {{IPAc-en|ə|ˈ|b|ɪ|l|ɪ|f|aɪ}} {{respell|ə|BIL|if|eye}} | tradename = Abilify, others | Drugs.com = {{drugs.com|monograph|aripiprazole}} | MedlinePlus = a603012 | DailyMedID = Aripiprazole | pregnancy_AU = C | pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Aripiprazole Use During Pregnancy | website=Drugs.com | date=22 August 2019 | url=https://www.drugs.com/pregnancy/aripiprazole.html | access-date=7 February 2020 | archive-date=12 November 2020 | archive-url=https://web.archive.org/web/20201112020613/https://www.drugs.com/pregnancy/aripiprazole.html | url-status=live }}</ref> | pregnancy_category = | routes_of_administration = By mouth, intramuscular | class = Atypical antipsychotic | ATC_prefix = N05 | ATC_suffix = AX12 | ATC_supplemental =  | legal_AU = S4 | legal_AU_comment = <ref>{{cite web | url= https://www.tga.gov.au/resources/prescription-medicines-registrations/aripena-sun-pharma-anz-pty-ltd| title= ARIPENA (Sun Pharma ANZ Pty Ltd) | website= tga.gov.au | publisher= Therapeutic Goods Administration, Government of Australia | date =| accessdate= December 8, 2025}}</ref> | legal_BR = C1 | legal_BR_comment = <ref>{{Cite web |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=Abilify Product information | website= health-products.canada.ca | publisher= Health Canada | date=19 March 2018 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=80782 | access-date= 16 February 2025}}</ref><ref>{{cite web | title=Abilify Asimtufii Product information | website= health-products.canada.ca | publisher= Health Canada | date=17 January 2025 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=104340 | access-date=16 February 2025}}</ref><ref>{{cite web | title=Abilify Maintena Product information | website= health-products.canada.ca | publisher= Health Canada | date=27 March 2014 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=90545 | access-date=16 February 2025}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ = Prescription only | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Abilify FDA label" /><ref name="Abilify Asimtufii FDA label" /><ref>{{cite web | title=Abilify Maintena- aripiprazole kit | website=DailyMed | date=30 January 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee49f3b1-1650-47ff-9fb1-ea53fe0b92b6 | access-date=16 February 2025}}</ref><ref>{{cite web | title=Abilify Mycite- aripiprazole tablet with sensor | website=DailyMed | date= 31 January 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8787c3f-5e41-42d1-8091-44b56346620f | access-date=16 February 2025}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Abilify EPAR">{{cite web | title=Abilify EPAR | website= ema.europa.eu| publisher= European Medicines Agency | date=4 June 2004 | url= https://www.ema.europa.eu/en/medicines/human/EPAR/abilify | access-date=4 July 2024 | archive-date=15 April 2024 | archive-url=https://web.archive.org/web/20240415010310/https://www.ema.europa.eu/en/medicines/human/EPAR/abilify | url-status= live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| bioavailability = 87%<ref name="Abilify FDA label" /><ref name = EMC>{{cite web|title=Abilify Tablets, Orodispersible Tablets, Oral Solution – Summary of Product Characteristics (SPC)|date=20 September 2013|access-date=22 October 2013|publisher=Otsuka Pharmaceuticals (UK) Ltd|website= medicines.org.uk |url=http://www.medicines.org.uk/emc/medicine/18494/SPC/Abilify+Tablets%2c+Orodispersible+Tablets%2c+Oral+Solution/|archive-url=https://web.archive.org/web/20160304001126/http://www.medicines.org.uk/emc/medicine/18494/SPC/Abilify+Tablets,+Orodispersible+Tablets,+Oral+Solution/|archive-date=4 March 2016}}</ref><ref name = EMA>{{cite web|title= Annex I Summary of Product Characteristics |website= ema.europa.eu| publisher= European Medicines Agency |access-date=22 October 2013|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000471/WC500020170.pdf|archive-date=23 October 2013|archive-url=https://web.archive.org/web/20131023060322/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000471/WC500020170.pdf}}</ref> | protein_bound = >99%<ref name="Abilify FDA label" /><ref name = EMC /><ref name = EMA /> | metabolism = Liver (mostly via CYP3A4 and 2D6<ref name="Abilify FDA label" /><ref name = EMC /><ref name = EMA />) | metabolites = Dehydroaripiprazole | onset = | elimination_half-life = 75 hours (active metabolite is 94 hours)<ref name="Abilify FDA label" /><ref name = EMC /><ref name = EMA /> | duration_of_action = | excretion = Kidney (27%; <1% unchanged) feces (60%; 18% unchanged)<ref name="Abilify FDA label" /><ref name = EMC /><ref name = EMA />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 129722-12-9 | CAS_supplemental = | PubChem = 60795 | IUPHAR_ligand = 34 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01238 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 54790 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 82VFR53I78 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01164 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 31236 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1112 | NIAID_ChemDB = | PDB_ligand = | synonyms = OPC-14597; OPC14597; OPC-31; OPC31; RDC-3317

| IUPAC_name = 7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1''H'')-one | C = 23 | H = 27 | Cl = 2 | N = 3 | O = 2 | SMILES = Clc4cccc(N3CCN(CCCCOc2ccc1c(NC(=O)CC1)c2)CC3)c4Cl | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C23H27Cl2N3O2/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18/h3-6,8,16H,1-2,7,9-15H2,(H,26,29) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CEUORZQYGODEFX-UHFFFAOYSA-N

| density = | density_notes = | melting_point = 138 | melting_high = 150 | melting_notes =<ref>{{cite web |title=Aripiprazole |url=https://www.thermofisher.com/order/catalog/product/457990050 |website=Thermofischer Scientific |access-date=April 11, 2026}}</ref> | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }} alt=A box of aripiprazole 15 mg tablets.|thumb|Aripiprazole 15 mg tablets '''Aripiprazole''', sold under the brand name '''Abilify''', among others, is a unique atypical antipsychotic<ref name="AHFS2019">{{cite web |title= Aripiprazole (Monograph) |url=https://www.drugs.com/monograph/aripiprazole.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=26 February 2019 |archive-date=26 November 2020 |archive-url=https://web.archive.org/web/20201126020237/https://www.drugs.com/monograph/aripiprazole.html |url-status=live }}</ref> primarily used in the treatment of schizophrenia, mania in bipolar disorder, and irritability associated with autism spectrum disorder;<ref name="AHFS2019" /> other uses include as an add-on treatment for major depressive disorder, obsessive–compulsive disorder, and tic disorders.<ref name= AHFS2019 /> Aripiprazole is taken by mouth or via injection into a muscle.<ref name= AHFS2019 />

It has generally favorable tolerability. Common side effects include restlessness, insomnia, transient weight gain, nausea, vomiting, constipation, dizziness, and mild sedation.<ref name="AHFS2019" /> Serious side effects may include neuroleptic malignant syndrome, tardive dyskinesia, and anaphylaxis.<ref name="AHFS2019" /> It is not recommended for older people with dementia-related psychosis due to an increased risk of death.<ref name= "AHFS2019" /> In pregnancy, there is evidence of possible harm to the fetus.<ref name="AHFS2019" /><ref>{{cite web|title=Prescribing medicines in pregnancy database|url= http://www.tga.gov.au/hp/medicines-pregnancy.htm| website= tga.gov.au | publisher= Therapeutic Goods Administration, Government of Australia |access-date=22 April 2014|date=3 March 2014|archive-date=8 April 2014|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm|url-status=live}}</ref> It is not recommended in women who are breastfeeding.<ref name= "AHFS2019" /> It has not been very well studied in people younger than 18.<ref name="AHFS2019" />

Aripiprazole is a pharmacologically unique atypical antipsychotic whose principal pharmacological action is as a functionally selective partial agonist at dopamine D2 receptors, stabilizing dopamine activity by enhancing signaling when levels are low and reducing it when levels are high. It also acts as a partial agonist at dopamine D3 and D4 receptors and at serotonin 5-HT1A and 5-HT2C receptors. It is a third-generation antipsychotic and its introduction led to a paradigm shift in antipsychotic drug development.

Aripiprazole was discovered in 1988 by Otsuka Pharmaceutical. It received approval for medical use in the United States in 2002<ref name=AHFS2019 /> and has since become available as a generic medication.<ref name= BNF76>{{cite book |title=British national formulary: BNF 76 |date=2018 |publisher= Pharmaceutical Press |isbn= 978-0-85711-338-2 |page=392 |edition= 76th}}</ref> In 2023, it was the 95th most commonly prescribed medication in the U.S., with more than 7{{nbsp}}million prescriptions.<ref>{{Cite web |title=The Top 300 of 2023 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |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.com}}</ref><ref>{{Cite web |title=Aripiprazole - Drug Usage Statistics, ClinCalc DrugStats Database |url=https://clincalc.com/DrugStats/Drugs/Aripiprazole |access-date=13 August 2025 |website=clincalc.com}}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">{{cite book | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free | vauthors = Organization WH }}</ref>

== Medical uses == Aripiprazole is primarily used for the treatment of schizophrenia or bipolar disorder.<ref name = EMA /><ref name= AHFS2019 /><ref name="Abilify FDA label">{{cite web | title=Abilify- aripiprazole tablet Abilify- aripiprazole solution Abilify- aripiprazole tablet, orally disintegrating Abilify- aripiprazole injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c040bd1d-45b7-49f2-93ea-aed7220b30ac | access-date=20 October 2020 | archive-date=3 December 2020 | archive-url=https://web.archive.org/web/20201203171648/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c040bd1d-45b7-49f2-93ea-aed7220b30ac | url-status=live }}</ref>

=== Schizophrenia === The 2016 National Institute for Health and Care Excellence (NICE) guidance for treating psychosis and schizophrenia in children and young people recommended aripiprazole as a second-line treatment after risperidone for people between 15 and 17 who are having an acute exacerbation or recurrence of psychosis or schizophrenia.<ref>{{cite web |title= Psychosis and schizophrenia in children and young people: recognition and management |url= https://www.nice.org.uk/guidance/cg155/chapter/Recommendations |website= National Institute for Health and Care Excellence |location= UK |date= October 2016 |access-date= 22 October 2018 |archive-date= 22 June 2020 |archive-url= https://web.archive.org/web/20200622164548/https://www.nice.org.uk/guidance/cg155/chapter/Recommendations |url-status= live }}</ref> A 2014 NICE review of the depot formulation of the drug found that it may have a role in treatment as an alternative to other depot formulations of second-generation antipsychotics for people who have trouble taking medication as directed or who prefer it.<ref>{{cite web |title= Schizophrenia: aripiprazole prolonged-release suspension for injection {{!}} Guidance and guidelines |url= https://www.nice.org.uk/advice/esnm39/chapter/Key-points-from-the-evidence |publisher= National Institute for Health and Care Excellence |location= UK |date= 24 July 2013 |access-date= 22 October 2018 |archive-date= 23 October 2018 |archive-url= https://web.archive.org/web/20181023120127/https://www.nice.org.uk/advice/esnm39/chapter/Key-points-from-the-evidence |url-status= live }}</ref>

A 2014 Cochrane review comparing aripiprazole and other atypical antipsychotics found it difficult to determine differences as data quality is poor.<ref>{{cite journal | vauthors = Khanna P, Suo T, Komossa K, Ma H, Rummel-Kluge C, El-Sayeh HG, Leucht S, Xia J | title = Aripiprazole versus other atypical antipsychotics for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | article-number = CD006569 | date = January 2014 | volume = 2014 | pmid = 24385408 | pmc = 4164478 | doi = 10.1002/14651858.CD006569.pub5 }}</ref> A 2011 Cochrane review comparing aripiprazole with placebo concluded that high dropout rates in clinical trials, and a lack of outcome data regarding general functioning, behavior, mortality, economic outcomes, or cognitive functioning make it difficult to definitively conclude that aripiprazole is useful in preventing relapse.<ref name="Coch2011">{{cite journal |vauthors=Belgamwar RB, El-Sayeh HG |date=August 2011 |title=Aripiprazole versus placebo for schizophrenia |journal=The Cochrane Database of Systematic Reviews |issue=8 |article-number=CD006622 |doi=10.1002/14651858.CD006622.pub2 |pmid=21833956 |pmc=12359115 }}</ref> This review found only low-quality evidence of effectiveness in treating schizophrenia.<ref name=Coch2011 />

A 2013 review placed aripiprazole in the middle range of 15 antipsychotics for effectiveness, approximately as effective as haloperidol and quetiapine<ref>{{cite journal | vauthors = Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, Arndt T, Bäckers L, Rothe P, Cipriani A, Davis J, Salanti G, Leucht S | title = Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis | journal = The Lancet | volume = 394 | issue = 10202 | pages = 939–951 | date = September 2019 | pmid = 31303314 | pmc = 6891890 | doi = 10.1016/S0140-6736(19)31135-3 }}</ref> and slightly more effective than ziprasidone, chlorpromazine, or asenapine, with better tolerability compared to the other antipsychotic drugs (4th best for reducing weight gain, 5th best for reducing extrapyramidal symptoms, the best for reducing prolactin levels, 2nd best for prolongated QTc interval, and 5th best for sedative symptoms). The authors concluded that for acute psychotic episodes, aripiprazole results in benefits in some aspects of the condition.<ref name= "Lancet2013">{{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 }}</ref> It lowers prolactin levels. In cases of hyperprolactinaemia caused by other antipsychotics, the addition of or switch to aripiprazole is used to lower prolactin levels.<ref>{{cite journal | vauthors = Labad J, Montalvo I, González-Rodríguez A, García-Rizo C, Crespo-Facorro B, Monreal JA, Palao D | title = Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: A systematic review and meta-analysis | journal = Schizophrenia Research | volume = 222 | pages = 88–96 | date = August 2020 | pmid = 32507371 | doi = 10.1016/j.schres.2020.04.031 }}</ref><ref>{{cite journal | vauthors = Besag FM, Vasey MJ, Salim I | title = Is Adjunct Aripiprazole Effective in Treating Hyperprolactinemia Induced by Psychotropic Medication? A Narrative Review | journal = CNS Drugs | volume = 35 | issue = 5 | pages = 507–526 | date = May 2021 | pmid = 33880739 | doi = 10.1007/s40263-021-00812-1 }}</ref>

Aripiprazole is recommended as the initial treatment for schizophrenia according to the INTEGRATE consensus international guidelines.<ref>{{cite journal | vauthors = McCutcheon RA, Pillinger T, Varvari I, Halstead S, Ayinde OO, Crossley NA, Correll CU, Hahn M, Howes OD, Kane JM, Kabir T, Konradsson-Geuken Å, Lennox B, Hui CL, Rossell SL, Solmi M, Sommer IE, Taipale H, Uchida H, Venkatasubramanian G, Warren N, Siskind D | title = INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia | journal = The Lancet. Psychiatry | volume = 12 | issue = 5 | pages = 384–394 | date = May 2025 | pmid = 40179920 | doi = 10.1016/S2215-0366(25)00031-8 | hdl = 11370/f265b554-cdb6-44c1-bd4e-f266fbf1a0f2 | hdl-access = free }}</ref>

In 2013 the World Federation of Societies for Biological Psychiatry recommended aripiprazole for treatment of acute exacerbations of schizophrenia as a Grade 1 recommendation and evidence level A.<ref name="Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ 2013 2–44">{{cite journal |vauthors=Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ |title=World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects |journal=The World Journal of Biological Psychiatry |volume=14 |issue=1 |pages=2–44 |date=February 2013 |pmid=23216388 |doi=10.3109/15622975.2012.739708 |s2cid=28750563}}</ref>

The British Association for Psychopharmacology similarly recommends that all persons presenting with psychosis receive treatment with an antipsychotic and that such treatment should continue for at least 1–2 years, as "There is no doubt that antipsychotic discontinuation is strongly associated with relapse during this period". The guideline further notes that "Established schizophrenia requires continued maintenance with doses of antipsychotic medication within the recommended range (Evidence level A)".<ref name="Barnes TR 2011 567–620">{{cite journal | vauthors = Barnes TR | title = Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology | journal = Journal of Psychopharmacology | volume = 25 | issue = 5 | pages = 567–620 | date = May 2011 | pmid = 21292923 | doi = 10.1177/0269881110391123 | s2cid = 40089561 }}</ref> thumb|250x250px|Abilify Maintena 400mg Intramuscular Syringe The British Association for Psychopharmacology<ref name="Barnes TR 2011 567–620" /> and the World Federation of Societies for Biological Psychiatry suggest there is little difference in effectiveness between antipsychotics in preventing relapse and recommend that the specific antipsychotic be chosen based on each person's preference and side effect profile. The latter group recommends switching to aripiprazole when excessive weight gain is encountered during treatment with other antipsychotics.<ref name="Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ 2013 2–44" />

=== Bipolar disorder === Aripiprazole is effective for the treatment of acute manic episodes of bipolar disorder in adults, children, and adolescents.<ref>{{cite web | url = http://www.nice.org.uk/guidance/cg185/chapter/1-recommendations | title = Bipolar disorder: assessment and management | quote = 1.1 Care for adults, children, and young people across all phases of bipolar disorder | website = Recommendations; Guidance and guidelines | date = 24 September 2014 | publisher = National Institute for Health and Care Excellence | location = UK | access-date = 1 December 2014 | archive-date = 6 August 2020 | archive-url = https://web.archive.org/web/20200806041846/https://www.nice.org.uk/guidance/cg185/chapter/1-Recommendations | url-status = live }}</ref><ref>{{cite journal | vauthors = Brown R, Taylor MJ, Geddes J | title = Aripiprazole alone or in combination for acute mania | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 12 | article-number = CD005000 | date = December 2013 | pmid = 24346956 | doi = 10.1002/14651858.CD005000.pub2 | pmc = 11330668 }}</ref> Used as maintenance therapy, it is useful for the prevention of manic episodes but is not for bipolar depression.<ref>{{cite journal | vauthors = De Fruyt J, Deschepper E, Audenaert K, Constant E, Floris M, Pitchot W, Sienaert P, Souery D, Claes S | title = Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis | journal = Journal of Psychopharmacology | volume = 26 | issue = 5 | pages = 603–617 | date = May 2012 | pmid = 21940761 | doi = 10.1177/0269881111408461 | s2cid = 57249815 | hdl = 2268/196468 | hdl-access = free }}</ref><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> Thus, it is often used in combination with an additional mood stabilizer; however, co-administration with a mood stabilizer increases the risk of extrapyramidal side effects.<ref>{{cite journal | vauthors = de Bartolomeis A, Perugi G | title = Combination of aripiprazole with mood stabilizers for the treatment of bipolar disorder: from acute mania to long-term maintenance | journal = Expert Opinion on Pharmacotherapy | volume = 13 | issue = 14 | pages = 2027–2036 | date = October 2012 | pmid = 22946707 | doi = 10.1517/14656566.2012.719876 | s2cid = 39065786 }}</ref> In September 2014, aripiprazole had a UK marketing authorization for up to 12 weeks of treatment for moderate to severe manic episodes in bipolar I disorder in young people aged 13 and older. Aripiprazole in doses of 2.5 mg can cause mania in those with bipolar disorder.<ref name="NICE2014B">{{cite web | title=1 Recommendations - Bipolar disorder: assessment and management - Guidance | publisher=National Institute for Health and Care Excellence | date=24 September 2014 | url=https://www.nice.org.uk/guidance/cg185/chapter/1-recommendations | access-date=3 April 2023 | archive-date=29 December 2021 | archive-url=https://web.archive.org/web/20211229193239/https://www.nice.org.uk/guidance/cg185/chapter/1-Recommendations | url-status=live }}</ref><ref>{{cite web | url=https://www.nice.org.uk/guidance/ta292/documents/bipolar-disorder-children-aripirazole-final-appraisal-determintation-document2 | title=Aripiprazole for treating moderate to severe manic episodes in adolescents with bipolar I disorder | publisher=National Institute for Health and Care Excellence | date=May 2013 | access-date=3 April 2023 | archive-date=4 November 2022 | archive-url=https://web.archive.org/web/20221104172557/http://www.nice.org.uk/guidance/ta292/documents/bipolar-disorder-children-aripirazole-final-appraisal-determintation-document2 | url-status=live }}</ref><ref>{{Cite journal |date=10 November 2014 |title=The risks and benefits of high dose antipsychotic medication |url=https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/college-reports/college-report-cr190.pdf?sfvrsn=54f5d9a2_2 |journal=Royal College of Psychiatrists |access-date=16 April 2024 |archive-date=4 July 2024 |archive-url=https://web.archive.org/web/20240704193012/https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/college-reports/college-report-cr190.pdf?sfvrsn=54f5d9a2_2 |url-status=live }}</ref>

=== Depression === Aripiprazole is an effective add-on treatment for major depressive disorder but increases the risk of side effects such as weight gain and movement disorders.<ref name= "Spielmans_2013">{{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 Medicine | volume = 10 | issue = 3 | article-number = e1001403 | date = March 2013 | pmid = 23554581 | pmc = 3595214 | doi = 10.1371/journal.pmed.1001403 | doi-access = free }}</ref><ref name= "pmid19687129">{{cite journal | vauthors = Nelson JC, Papakostas GI | title = Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials | journal = The American Journal of Psychiatry | volume = 166 | issue = 9 | pages = 980–991 | date = September 2009 | pmid = 19687129 | doi = 10.1176/appi.ajp.2009.09030312 | doi-access = free | title-link = doi }}</ref><ref name= "pmid21154393">{{cite journal | vauthors = Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S | title = Second-generation antipsychotics for major depressive disorder and dysthymia | journal = The Cochrane Database of Systematic Reviews | issue = 12 | article-number = CD008121 | date = December 2010 | volume = 2012 | pmid = 21154393 | doi = 10.1002/14651858.CD008121.pub2 | pmc = 11994262 }}</ref> The overall benefit is small to moderate and its use appears to improve neither quality of life nor functioning.<ref name= "Spielmans_2013" /> Aripiprazole may interact with some antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) that are metabolized by CYP2D6. There are known interactions with fluoxetine and paroxetine<ref>{{cite journal | vauthors = Azuma J, Hasunuma T, Kubo M, Miyatake M, Koue T, Higashi K, Fujiwara T, Kitahara S, Katano T, Hara S | title = The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine | journal = European Journal of Clinical Pharmacology | volume = 68 | issue = 1 | pages = 29–37 | date = January 2012 | pmid = 21739267 | pmc = 3249179 | doi = 10.1007/s00228-011-1094-4 }}</ref> and lesser interactions with sertraline, escitalopram, citalopram and fluvoxamine. CYP2D6 inhibitors increase aripiprazole concentrations by 2–3 times.<ref name = Abilify /> When strong CYP2D6 SSRIs (such as fluoxetine and paroxetine) are co-administered, the Food and Drug Administration (FDA) recommends dose monitoring, although it is not clear the SSRI dose should be lowered.<ref name="Abilify FDA label" /><ref>{{cite journal | vauthors = Hahn M, Roll SC | title = Dosing Recommendations of Aripiprazole Depot with Strong Cytochrome P450 3A4 Inhibitors: A Relapse Risk | journal = Drug Safety: Case Reports | volume = 3 | issue = 1 | article-number = 5 | date = December 2016 | pmid = 27747685 | pmc = 5005780 | doi = 10.1007/s40800-016-0027-7 }}</ref><ref>{{cite journal | vauthors = Jallaq SA, Verba M, Strawn JR, Martin LJ, DelBello MP, Ramsey LB | title = CYP2D6 Phenotype Influences Aripiprazole Tolerability in Pediatric Patients with Mood Disorders | journal = Journal of Child and Adolescent Psychopharmacology | volume = 31 | issue = 1 | pages = 56–62 | date = February 2021 | pmid = 32845723 | pmc = 8255312 | doi = 10.1089/cap.2020.0058 }}</ref><ref>{{cite journal | vauthors = Hoffelt C, Gross T | title = A review of significant pharmacokinetic drug interactions with antidepressants and their management | journal = The Mental Health Clinician | volume = 6 | issue = 1 | pages = 35–41 | date = January 2016 | pmid = 29955445 | pmc = 6009245 | doi = 10.9740/mhc.2016.01.035 }}</ref>

=== Autism === Short-term data (8 weeks) shows reduced irritability, hyperactivity, inappropriate speech, and stereotypy, but no change in lethargic behaviors.<ref name =Hirsch2016>{{cite journal | vauthors = Hirsch LE, Pringsheim T | title = Aripiprazole for autism spectrum disorders (ASD) | journal = The Cochrane Database of Systematic Reviews | issue = 6 | article-number = CD009043 | date = June 2016 | volume = 2016 | pmid = 27344135 | pmc = 7120220 | doi = 10.1002/14651858.CD009043.pub3 }}</ref> Adverse effects include weight gain, sleepiness, drooling, and tremors.<ref name=Hirsch2016 /> It is suggested that children and adolescents need to be monitored regularly while taking this medication to evaluate if this treatment option is still effective after long-term use and note if side effects are worsening. Further studies are needed to understand if this drug is helpful for children after long-term use.<ref name=Hirsch2016 />

=== Tic disorders === Aripiprazole is approved for the treatment of Tourette syndrome and other tic disorders.<ref name="AdisInsight">{{cite web |title=Aripiprazole |url=http://adisinsight.springer.com/drugs/800001612 |access-date=21 September 2021 |publisher=Springer |website=adisInsight. springer.com |archive-date=2 October 2017 |archive-url=https://web.archive.org/web/20171002174227/http://adisinsight.springer.com/drugs/800001612 |url-status=live }}</ref><ref name="pmid29154107">{{cite journal | vauthors = Janik P, Szejko N | title = Aripiprazole in treatment of Gilles de la Tourette syndrome – New therapeutic option | journal = Neurologia I Neurochirurgia Polska | volume = 52 | issue = 1 | pages = 84–87 | date = 2018 | pmid = 29154107 | doi = 10.1016/j.pjnns.2017.10.015 | url = https://journals.viamedica.pl/neurologia_neurochirurgia_polska/article/view/61311 | access-date = 20 November 2021 | archive-date = 24 December 2022 | archive-url = https://web.archive.org/web/20221224140235/https://journals.viamedica.pl/neurologia_neurochirurgia_polska/article/view/61311 | url-status = live }}</ref><ref name="Müller-Vahl_2022">{{cite journal | vauthors = Müller-Vahl KR, Szejko N, Verdellen C, Roessner V, Hoekstra PJ, Hartmann A, Cath DC | title = European clinical guidelines for Tourette syndrome and other tic disorders: summary statement | journal = European Child & Adolescent Psychiatry | volume = 31 | issue = 3 | pages = 377–382 | date = March 2022 | pmid = 34244849 | pmc = 8940881 | doi = 10.1007/s00787-021-01832-4 }}</ref> There is evidence supporting that it is effective, safe, and well-tolerated for this use per systematic reviews and meta-analyses.<ref name= "pmid28441584">{{cite journal | vauthors = Wang S, Wei YZ, Yang JH, Zhou YM, Cheng YH, Yang C, Zheng Y | title = The efficacy and safety of aripiprazole for tic disorders in children and adolescents: A systematic review and meta-analysis | journal = Psychiatry Research | volume = 254 | issue = | pages = 24–32 | date = August 2017 | pmid = 28441584 | doi = 10.1016/j.psychres.2017.04.013 | s2cid = 13792422 }}</ref><ref name= "pmid29388585">{{cite journal | vauthors = Cox JH, Seri S, Cavanna AE | title = Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders | journal = Pediatric Health, Medicine and Therapeutics | volume = 7 | issue = | pages = 57–64 | date = 2016 | pmid = 29388585 | pmc = 5683285 | doi = 10.2147/PHMT.S87121 | doi-access = free }}</ref><ref name="pmid26310194">{{cite journal | vauthors = Zheng W, Li XB, Xiang YQ, Zhong BL, Chiu HF, Ungvari GS, Ng CH, Lok GK, Xiang YT | title = Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis | journal = Human Psychopharmacology | volume = 31 | issue = 1 | pages = 11–18 | date = January 2016 | pmid = 26310194 | doi = 10.1002/hup.2498 | s2cid = 5353158 }}</ref><ref name="pmid26220447">{{cite journal | vauthors = Yang CS, Huang H, Zhang LL, Zhu CR, Guo Q | title = Aripiprazole for the treatment of tic disorders in children: a systematic review and meta-analysis | journal = BMC Psychiatry | volume = 15 | issue = | article-number = 179 | date = July 2015 | pmid = 26220447 | pmc = 4518630 | doi = 10.1186/s12888-015-0504-z | doi-access = free }}</ref>

=== Obsessive–compulsive disorder === A 2014 systematic review and meta-analysis concluded that add-on therapy with low-dose aripiprazole is an effective treatment for obsessive–compulsive disorder (OCD) that does not improve with selective serotonin reuptake inhibitors (SSRIs) alone.<ref name="pmid25432131">{{cite journal | vauthors = Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J | title = Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis | journal = BMC Psychiatry | volume = 14 | issue = 1 | article-number = 317 | date = November 2014 | pmid = 25432131 | pmc = 4262998 | doi = 10.1186/s12888-014-0317-5 | doi-access = free }}</ref> The conclusion was based on the results of two relatively small, short-term trials, each of which demonstrated improvements in symptoms.<ref name="pmid25432131" /><ref>{{cite journal | vauthors = Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J | title = Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis | journal = BMC Psychiatry | volume = 14 | article-number = 317 | date = November 2014 | pmid = 25432131 | pmc = 4262998 | doi = 10.1186/s12888-014-0317-5 | doi-access = free }}</ref><ref name= "pmid17849776">{{cite journal | vauthors = Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB | title = Practice guideline for the treatment of patients with obsessive-compulsive disorder | journal = The American Journal of Psychiatry | volume = 164 | issue = 7 Suppl | pages = 5–53 | date = July 2007 | pmid = 17849776 }}</ref><ref>{{cite journal | vauthors = Fornaro M, Gabrielli F, Mattei C, Vinciguerra V, Fornaro P | title = Aripiprazole augmentation in poor insight obsessive-compulsive disorder: a case report | journal = Annals of General Psychiatry | volume = 7 | issue = 1 | article-number = 26 | date = December 2008 | pmid = 19105842 | pmc = 2621216 | doi = 10.1186/1744-859X-7-26 | doi-access = free }}</ref> However, aripiprazole is cautiously recommended by a 2017 review on antipsychotics for OCD.<ref name= "Pignon et al Review">{{cite journal | vauthors = Pignon B, Tezenas du Montcel C, Carton L, Pelissolo A | title = The Place of Antipsychotics in the Therapy of Anxiety Disorders and Obsessive-Compulsive Disorders | journal = Current Psychiatry Reports | volume = 19 | issue = 12 | article-number = 103 | date = November 2017 | pmid = 29110139 | doi = 10.1007/s11920-017-0847-x | s2cid = 41312623 }}</ref> Aripiprazole is not currently approved for the treatment of OCD and is instead used off-label for this indication.<ref name="AdisInsight" />

=== Sleep disorders === Studies indicate low-dose aripiprazole (0.5–3 mg) can be used to treat Delayed Sleep Phase Syndrome (DSPS), a persistent or recurrent pattern of sleep disturbances that lead to insomnia and/or excessive daytime sleepiness, and impaired functioning in social, occupational, or other spheres.<ref>{{cite journal | vauthors = Takaki M, Ujike H | title = Aripiprazole is effective for treatment of delayed sleep phase syndrome | journal = Clinical Neuropharmacology | volume = 37 | issue = 4 | pages = 123–124 | date = 2014 | pmid = 24992089 | doi = 10.1097/WNF.0000000000000035 }}</ref>

===Available forms=== {{See also|Aripiprazole lauroxil}} alt=Two tablets of aripiprazole 15 mg.|thumb|Aripiprazole 15 mg tablets Aripiprazole is available in the form of oral tablets, oral films, oral disintegrating tablets, oral solution, digital pills with sensors, and as a short-acting injectable for intramuscular administration.<ref>{{Cite web |title=Aripiprazole: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a603012.html |access-date=2026-01-20 |website=medlineplus.gov |language=en}}</ref><ref>{{Cite journal |date=2020-02-01 |title=Digital drug fortunes falter |url=https://www.nature.com/articles/s41587-020-0425-3 |journal=Nature Biotechnology |language=en |volume=38 |issue=2 |pages=117 |doi=10.1038/s41587-020-0425-3 |pmid=32034387 |issn=1546-1696}}</ref> It is also available as a long-acting injectable, aripiprazole lauroxil, a lipophilic ester prodrug of aripiprazole designed to be given once per month,<ref>{{cite book | vauthors = Gettu N, Saadabadi A | chapter = Aripiprazole |date=2025 | title = StatPearls | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK547739/ |access-date=2026-01-18 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31613519 }}</ref> and as a once every two months long-acting injectable, under the brand name Abilify Asimtufii.<ref>{{Cite web | vauthors = Antrim A |date=2026-01-20 |title=FDA Approves Aripiprazole as First Once-Every-2-Months Long-Acting Injectable for Schizophrenia, Bipolar I Disorder | work = Pharmacy Times |url=https://www.pharmacytimes.com/view/fda-approves-aripiprazole-as-first-once-every-2-months-long-acting-injectable-for-schizophrenia-bipolar-i-disorder |access-date=2026-01-20 |language=en}}</ref>

== Contraindications == Contraindications to aripiprazole include known hypersensitivity to aripiprazole, among others.<ref name="AHFS2019" />

== Adverse effects == {{See also|List of adverse effects of aripiprazole}}

In elderly people with dementia-related psychosis who are treated with antipsychotics, there is an increased risk of death.<ref name="MedlinePlus">{{cite web |title=Aripiprazole: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a603012.html |website=MedlinePlus |access-date=13 October 2023 |archive-date=4 October 2023 |archive-url=https://web.archive.org/web/20231004231705/https://medlineplus.gov/druginfo/meds/a603012.html |url-status=live}}</ref> In children, adolescents, and young adults treated with antidepressants there is an increased risk of suicidal thoughts or behavior.<ref name="Abilify FDA label" />

In adults, side effects with greater than 10% incidence include weight gain, mania, headache, akathisia, insomnia, delirium, and gastrointestinal effects like nausea, constipation, and lightheadedness.<ref name="Abilify FDA label" /><ref name = EMC /><ref name = EMA /><ref name = Abilify /><ref name="WebMD">{{cite web |title=Abilify Discmelt, Abilify Maintena (aripiprazole) dosing, indications, interactions, adverse effects, and more |url=http://reference.medscape.com/drug/abilify-discmelt-abilify-maintena-aripiprazole-342983 |url-status=live |archive-url=https://web.archive.org/web/20131023060856/http://reference.medscape.com/drug/abilify-discmelt-abilify-maintena-aripiprazole-342983 |archive-date=23 October 2013 |access-date=22 October 2013 |website=Medscape Reference |publisher=WebMD}}</ref> Side effects in children are similar, and include sleepiness, increased appetite, and stuffy nose.<ref name = Abilify />

In 2016, an FDA Drug Safety Communication warned that aripiprazole can rarely cause impulse control issues.<ref>{{cite web |date=9 February 2019 |title=l FDA warns about new impulse-control problems associated with mental health drug aripiprazole (Abilify, Abilify Maintena, Aristada) |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-new-impulse-control-problems-associated-mental-health |website=FDA.gov |publisher=U.S. Food and Drug Administration (FDA) |access-date=3 April 2023 |archive-date=2 April 2023 |archive-url=https://web.archive.org/web/20230402021450/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-new-impulse-control-problems-associated-mental-health }}</ref> The impulse control problems include a strong desire to gamble, binge eat, shop, and engage in sexual activity.<ref name="FDA impulse control">{{cite web |date=3 May 2016 |title=Aripiprazole (Abilify, Abilify Maintena, Aristada): Drug Safety Communication – FDA Warns About New Impulse-control Problems |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-new-impulse-control-problems-associated-mental-health |access-date=4 May 2016 |website=U.S. Food and Drug Administration (FDA) |archive-date=2 May 2019 |archive-url=https://web.archive.org/web/20190502101304/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-new-impulse-control-problems-associated-mental-health }}</ref><ref name="pmid26658263">{{cite journal | vauthors = Grall-Bronnec M, Sauvaget A, Perrouin F, Leboucher J, Etcheverrigaray F, Challet-Bouju G, Gaboriau L, Derkinderen P, Jolliet P, Victorri-Vigneau C | title = Pathological Gambling Associated With Aripiprazole or Dopamine Replacement Therapy: Do Patients Share the Same Features? A Review | journal = Journal of Clinical Psychopharmacology | volume = 36 | issue = 1 | pages = 63–70 | date = February 2016 | pmid = 26658263 | pmc = 4700874 | doi = 10.1097/JCP.0000000000000444 }}</ref> These urges can be uncontrollable. The uncontrollable urges were reported to stop when the dose of aripiprazole was lowered or the medication was discontinued.<ref name="FDA impulse control" />

Uncontrolled movement such as restlessness, tremors, and muscle rigidity may also occur.<ref name="Abilify" />

=== Discontinuation === The British National Formulary recommends gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref>{{cite book | editor = 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.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book |vauthors=Haddad P, Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=978-0-19-852748-0 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |access-date=19 September 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110164012/https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |url-status=live }}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004 /> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004 /> Symptoms generally resolve after a short period of time.<ref name=Had2004 />

There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a part of a withdrawal syndrome.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book |vauthors=Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=978-88-470-2679-7 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |access-date=19 September 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110164029/https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |url-status=live }}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004 />

== Overdose == Children or adults who ingested acute overdoses have usually manifested central nervous system depression ranging from mild sedation to coma; serum concentrations of aripiprazole and dehydroaripiprazole, the primary active metabolite of aripiprazole, in these people were elevated by up to 3–4 fold over normal therapeutic levels; as of 2008, no deaths had been recorded.<ref>{{cite book | vauthors = Baselt RC | title = Disposition of Toxic Drugs and Chemicals in Man | date = 2008 | publisher = Biomedical Publications | location = Foster City, CA | isbn = 978-0-9626523-7-0 | edition = 8th | pages = 105–6 }}</ref><ref name="Skov 2015 41-44">{{cite journal | vauthors = Skov L, Johansen SS, Linnet K | title = Postmortem femoral blood reference concentrations of aripiprazole, chlorprothixene, and quetiapine | journal = Journal of Analytical Toxicology | volume = 39 | issue = 1 | pages = 41–44 | date = Jan 2015 | pmid = 25342720 | doi = 10.1093/jat/bku121 | doi-access = free | title-link = doi }}</ref>

== Interactions == Aripiprazole is a substrate of CYP2D6 and CYP3A4. Coadministration with medications that inhibit (e.g. paroxetine, fluoxetine) or induce (e.g. carbamazepine) these metabolic enzymes are known to increase and decrease, respectively, plasma levels of aripiprazole.<ref name="drugLabelWP">{{cite web | url = http://www.druglib.com/druginfo/abilify/warnings_precautions/ | title = Abilify (Aripiprazole) – Warnings and Precautions | access-date = 8 December 2008 | publisher = DrugLib.com | date = 14 February 2007 | archive-url = https://web.archive.org/web/20081204161824/http://www.druglib.com/druginfo/abilify/warnings_precautions/ | archive-date= 4 December 2008 | url-status= live}}</ref><ref name="Abilify FDA label" />

Precautions should be taken in people with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics along with other medications that affect blood sugar levels and should be monitored regularly for worsening of glucose control. The liquid form (oral solution) of this medication may contain up to 15 grams of sugar per dose.<ref name=AHFS2019 />

Antipsychotics like aripiprazole and stimulant medications, such as amphetamine, are traditionally thought to have opposing effects because both drugs affect dopaminergic neurons, but both stimulants and antipsychotics increase synaptic dopamine levels.<ref>{{cite journal | vauthors = Westerink BH, Kawahara Y, De Boer P, Geels C, De Vries JB, Wikström HV, Van Kalkeren A, Van Vliet B, Kruse CG, Long SK | title = Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum | journal = European Journal of Pharmacology | volume = 412 | issue = 2 | pages = 127–138 | date = January 2001 | pmid = 11165224 | doi = 10.1016/S0014-2999(00)00935-3 }}</ref> In antipsychotics, this is caused by the inhibition of dopamine autoreceptors as well as the effects of antipsychotics on non-dopaminergic receptors; in amphetamine this is caused by non-competitive inhibition of dopamine reuptake and agonism of intracellular TAAR1. Therefore, aripiprazole may interact with amphetamine to synergistically increase postsynaptic levels of dopamine. This interaction frequently occurs in the setting of comorbid attention deficit hyperactivity disorder (ADHD, for which stimulants are commonly prescribed) and off-label treatment of aggression with antipsychotics.

Aripiprazole has been reported to provide some benefit in improving cognitive functioning in people with ADHD without other psychiatric comorbidities, though the results have been disputed. The combination of antipsychotics like aripiprazole with stimulants should not be considered an absolute contraindication.<ref name="Yanofski review">{{cite journal | vauthors = Yanofski J | title = The dopamine dilemma: using stimulants and antipsychotics concurrently | journal = Psychiatry | volume = 7 | issue = 6 | pages = 18–23 | date = June 2010 | pmid = 20622942 | pmc = 2898838 }}</ref>

== Pharmacology == === Pharmacodynamics === {{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}

{| class="wikitable floatright" style="font-size:small;" |+ Aripiprazole<ref name="PDSP">{{cite web | title = PDSP Ki Database | website = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=aripiprazole&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | archive-date = 27 August 2021 | archive-url = https://web.archive.org/web/20210827224128/https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=aripiprazole&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | url-status = live }}</ref><ref name="pmid12784105">{{cite journal | vauthors = Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, Roth BL, Mailman R | title = Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology | journal = Neuropsychopharmacology | volume = 28 | issue = 8 | pages = 1400–1411 | date = August 2003 | pmid = 12784105 | doi = 10.1038/sj.npp.1300203 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Mohr P, Masopust J, Kopeček M | title = Dopamine Receptor Partial Agonists: Do They Differ in Their Clinical Efficacy? | journal = Frontiers in Psychiatry | volume = 12 | article-number = 781946 | date = 25 January 2022 | pmid = 35145438 | pmc = 8821167 | doi = 10.3389/fpsyt.2021.781946 | doi-access = free }}</ref> |- ! Site !! Ki (nM) ! IA (%) !! Action !! Ref |- | {{abbrlink|SERT|Serotonin transporter}} || 900–1260 | || Reuptake inhibitor || <ref name="pmid12665420" /><ref name="pmid12784105" /> |- | {{abbrlink|NET|Norepinephrine transporter}} || 1340–2840 | || Reuptake inhibitor || <ref name="pmid12784105" /> |- | {{abbrlink|DAT|Dopamine transporter}} || 2560–3880 | || Reuptake inhibitor || <ref name="pmid12784105" /> |- | 5-HT1AL || 1.7–6.4 | 68% || Partial agonist / functional full agonist|| <ref name="pmid12784105" /><ref name="pmid12629531">{{cite journal | vauthors = Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL | title = H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs | journal = Neuropsychopharmacology | volume = 28 | issue = 3 | pages = 519–526 | date = March 2003 | pmid = 12629531 | doi = 10.1038/sj.npp.1300027 | doi-access = free | title-link = doi }}</ref><ref name="pmid12665420">{{cite journal | vauthors = Keck PE, McElroy SL | title = Aripiprazole: a partial dopamine D2 receptor agonist antipsychotic | journal = Expert Opinion on Investigational Drugs | volume = 12 | issue = 4 | pages = 655–662 | date = April 2003 | pmid = 12665420 | doi = 10.1517/13543784.12.4.655 | s2cid = 8654102 }}</ref> |- | 5-HT1B || 570–1090 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | 5-HT1D || 57–79 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | 5-HT1E || 3000 – >10,000 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | 5-HT2AL || 6.7–39 | 0–52% || Partial agonist / functional full agonist | <ref name="GaitondeAvetdelaFuenteRevenga2024">{{cite journal | vauthors = Gaitonde SA, Avet C, de la Fuente Revenga M, Blondel-Tepaz E, Shahraki A, Pastor AM, Talagayev V, Robledo P, Kolb P, Selent J, González-Maeso J, Bouvier M | title = Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor | journal = Mol Psychiatry | volume = 29 | issue = 9 | pages = 2753–2764 | date = September 2024 | pmid = 38561467 | pmc = 11420065 | doi = 10.1038/s41380-024-02531-7 | url = }}</ref><ref name="pmid12665420" /><ref name="pmid12784105" /><ref name="pmid12629531" /> |- | 5-HT2B || 0.25–0.47 | || Inverse agonist || <ref name="pmid12784105" /> |- | 5-HT2CL || 11–197 | 82% || Partial agonist / functional full agonist || <ref name="pmid12665420" /><ref name="pmid12784105" /><ref name="pmid12629531" /> |- | 5-HT3 || 520–740 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | 5-HT5A || 960–1520 | 87% || Near-full Agonist || <ref name="pmid12784105" /> |- | 5-HT6 || 475–665 | || Antagonist || <ref name="pmid12665420" /><ref name="pmid12784105" /><ref name="pmid12629531" /> |- | 5-HT7L || 6.6–14 | 58% || Partial agonist / functional full agonist | <ref name="pmid12784105" /><ref name="pmid12629531" /><ref name="pmid12665420" /> |- | α1A || 25.7 | || Antagonist || <ref name="pmid12784105" /><ref name="pmid12629531" /> |- | α1B || 35 | || Antagonist || <ref name="pmid12784105" /> |- | α2A || 74.3 | || Antagonist || <ref name="pmid12784105" /><ref name="pmid12629531" /> |- | α2B || 103 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /><ref name="pmid12629531" /> |- | α2C || 38 | || Antagonist || <ref name="pmid12784105" /><ref name="pmid12629531" /> |- | β1 || 141 | || Agonist || <ref name="pmid12784105" /> |- | β2 || 163 | || Agonist || <ref name="pmid12784105" /> |- | D1L || 1290–2630 | || Agonist || <ref name="pmid12665420" /><ref name="pmid12784105" /> |- | D2S || 2.2–4.4 | ~60% || Partial agonist / functional antagonist || <ref name="pmid12784105" /> |- | D2L | 0.65–0.83 | ~58% | Partial agonist / functional full agonist | |- | D3S || 4.3–15.1 | ~40% || Partial agonist / functional antagonist || <ref name="pmid12665420" /><ref name="pmid12784105" /> |- | D4L || 417–603 | ~30% || Partial agonist / functional full agonist || <ref name="pmid12665420" /><ref name="pmid12784105" /> |- | D5L || 1240–3940 | || Agonist || <ref name="pmid12665420" /><ref name="pmid12784105" /> |- | H1 || 22.5–27.7 | || Neutral Antagonist | <ref name="pmid12784105" /><ref name="pmid12629531" /><ref name="pmid12665420" /> |- | H2 || >10,000 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | H3 || 60–388 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | H4 || >10,000 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | M1|| 6,780 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | M2 || 3,510 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | M3 || 4,680 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /><ref name="pmid12629531" /> |- | M4 || 1,520 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | M5 || 2,330 | || {{abbr|ND|No data}} || <ref name="pmid12784105" /> |- | GABAA-ρ | | || Orthosteric Negative allosteric modulator |- | {{abbr|NMDA|N-Methyl-D-aspartate receptor}} ({{abbr|PCP1|Phencyclidine site}}) | 1.824 | || Uncompetitive channel blocker / Antagonist | <ref name="pmid12784105" /> |- | | {{abbr|NMDA|N-Methyl-D-aspartate receptor}} ({{abbr|PCP2|Phencyclidine site}}) | 1.824 | || Uncompetitive channel blocker / Antagonist | <ref name="pmid12784105" /> |- class="sortbottom" | colspan="5" style="width: 1px;" | Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except 5-HT3 (rat), D4 (human/rat), H3 (guinea pig), and NMDA/PCP (rat).<ref name="pmid12784105" /> IA = Intrinsic Activity |}

Aripiprazole's mechanism of action is different from those of the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone).<ref name="Starrenburga 2009 164–170">{{cite journal | vauthors = Starrenburg FC, Bogers JP | title = How can antipsychotics cause Diabetes Mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins | journal = European Psychiatry | volume = 24 | issue = 3 | pages = 164–170 | date = April 2009 | pmid = 19285836 | doi = 10.1016/j.eurpsy.2009.01.001 | s2cid = 42636469 }}</ref><ref name="drugLabelPC" /><ref name=Goodman>{{cite book| vauthors = Brunton L |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics | edition = 12th |year=2011|publisher=McGraw-Hill|location=China|isbn=978-0-07-162442-8|pages=406–410}}</ref><ref name="Davies_2004">{{cite journal | vauthors = Davies MA, Sheffler DJ, Roth BL | title = Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology | journal = CNS Drug Reviews | volume = 10 | issue = 4 | pages = 317–336 | year = 2004 | pmid = 15592581 | pmc = 6741761 | doi = 10.1111/j.1527-3458.2004.tb00030.x | author3-link = Bryan Roth }}</ref> It shows differential engagement at the dopamine receptor (D2<ref name="pmid12784105" />) and acts as a partial agonist of this receptor. It is also a partial agonist of the serotonin 5-HT1A receptor. In addition, it is a weak partial agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.<ref name="LiYanChen2025">{{cite journal | vauthors = Li R, Yan H, Chen Y, Liu Y, Tang L, Yu J, Liu J, Wang H, Wang S, Cheng J | title = Structure-Guided Design of Novel 5-HT2A Partial Agonists as Psychedelic Analogues with Antidepressant Effects | journal = J Med Chem | volume = 68| issue = 20| pages = 21683–21700| date = October 2025 | pmid = 41087124 | doi = 10.1021/acs.jmedchem.5c02045 | url = }}</ref><ref name="ChenFanWang2022">{{cite journal | vauthors = Chen Z, Fan L, Wang H, Yu J, Lu D, Qi J, Nie F, Luo Z, Liu Z, Cheng J, Wang S | title = Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties | journal = Nat Neurosci | volume = 25 | issue = 1 | pages = 39–49 | date = January 2022 | pmid = 34887590 | doi = 10.1038/s41593-021-00971-w | url = }}</ref><ref name="PaeSerrettiPatkar2008">{{cite journal | vauthors = Pae CU, Serretti A, Patkar AA, Masand PS | title = Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence | journal = CNS Drugs | volume = 22 | issue = 5 | pages = 367–388 | date = 2008 | pmid = 18399707 | doi = 10.2165/00023210-200822050-00002 | s2cid = 19757151 }}</ref><ref name="TuplinHolahan2017">{{cite journal | vauthors = Tuplin EW, Holahan MR | title = Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity | journal = Current Neuropharmacology | volume = 15 | issue = 8 | pages = 1192–1207 | date = November 2017 | pmid = 28412910 | pmc = 5725548 | doi = 10.2174/1570159X15666170413115754 }}</ref>

It appears to show predominantly partial agonistic activity on postsynaptic dopamine D2 receptors and partial agonist activity on presynaptic dopamine D2 receptors,<ref name="pmid17501690">{{cite journal | vauthors = Wood M, Reavill C | title = Aripiprazole acts as a selective dopamine D2 receptor partial agonist | journal = Expert Opinion on Investigational Drugs | volume = 16 | issue = 6 | pages = 771–775 | date = June 2007 | pmid = 17501690 | doi = 10.1517/13543784.16.6.771 | s2cid = 42171115 }}</ref> D3,<ref name="pmid12784105" /><ref name="kegeles">{{cite journal | vauthors = Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA, Gonzales R, Kim JH, Alvarez B, Gil R, Laruelle M, Abi-Dargham A | title = Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride | journal = Neuropsychopharmacology | volume = 33 | issue = 13 | pages = 3111–3125 | date = December 2008 | pmid = 18418366 | doi = 10.1038/npp.2008.33 | doi-access = free | title-link = doi }}</ref><ref name="pmid12093598">{{cite journal | vauthors = Yokoi F, Gründer G, Biziere K, Stephane M, Dogan AS, Dannals RF, Ravert H, Suri A, Bramer S, Wong DF | title = Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride | journal = Neuropsychopharmacology | volume = 27 | issue = 2 | pages = 248–259 | date = August 2002 | pmid = 12093598 | doi = 10.1016/S0893-133X(02)00304-4 | doi-access = free | title-link = doi }}</ref> and partially D4<ref name="pmid12784105" /><ref name="drugLabelPC" /> and is a partial activator of serotonin (5-HT1A,<ref name="pmid12784105" /><ref name="pmid12063084">{{cite journal | vauthors = Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA | title = The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor | journal = European Journal of Pharmacology | volume = 441 | issue = 3 | pages = 137–140 | date = April 2002 | pmid = 12063084 | doi = 10.1016/S0014-2999(02)01532-7 }}</ref><ref name="pmid17728427" /> 5-HT2A,<ref name="pmid12784105" /> 5-HT2B,<ref name="pmid12784105" /> 5-HT6, and 5-HT7).<ref name="pmid12784105" /><ref name="Davies_2004" /> It also shows lower effect on histamine (H1), as well as the serotonin transporter.<ref name="pmid12784105" /><ref name="drugLabelPC" /> Aripiprazole acts by modulating neurotransmission overactivity of dopamine, which is thought to mitigate schizophrenia symptoms.<ref name="pmid19909227">{{cite journal | vauthors = Mailman RB, Murthy V | title = Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? | journal = Current Pharmaceutical Design | volume = 16 | issue = 5 | pages = 488–501 | date = May 2010 | pmid = 19909227 | pmc = 2958217 | doi = 10.2174/138161210790361461 }}</ref>

As a pharmacologically unique antipsychotic with pronounced functional selectivity, characterization of this dopamine D2 partial agonist (with an intrinsic activity of ~50%)<ref>{{cite journal | vauthors = Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB | title = Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 302 | issue = 1 | pages = 381–389 | date = July 2002 | pmid = 12065741 | doi = 10.1124/jpet.102.033175 | s2cid = 12919430 }}</ref> as being similar to a full agonist but at a reduced level of activity presents a misleading oversimplification of its actions; for example, among other effects, aripiprazole has been shown, in vitro, to bind to and/or induce receptor conformations (i.e., facilitate receptor shapes) in such a way as to not only prevent receptor internalization (and, thus, lower receptor density) but even to lower the rate of receptor internalization below that of neurons not in the presence of agonists (including dopamine) or antagonists.<ref>{{cite journal | vauthors = Urban JD, Vargas GA, von Zastrow M, Mailman RB | title = Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signaling pathways | journal = Neuropsychopharmacology | volume = 32 | issue = 1 | pages = 67–77 | date = January 2007 | pmid = 16554739 | doi = 10.1038/sj.npp.1301071 | s2cid = 31846731 | doi-access = free | title-link = doi }}</ref>

It is often the nature of partial agonists, including aripiprazole, to display a stabilizing effect (such as on mood in this case) with agonistic activity when there are low levels of endogenous neurotransmitters (such as dopamine) and antagonistic activity in the presence of high levels of agonists associated with events such as mania, psychosis, and drug use. In addition to aripiprazole's partial agonism and functional selectivity characteristics, its effectiveness may be mediated by its very high dopamine D2 receptor occupancy (approximately 31%, 44%, 75%, 80%, and 95% at daily dosages of 0.5 mg, 2 mg, 10 mg, 30 mg and 40 mg respectively)<ref>{{cite journal | vauthors = Yokoi F, Gründer G, Biziere K, Stephane M, Dogan AS, Dannals RF, Ravert H, Suri A, Bramer S, Wong DF | title = Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride | journal = Neuropsychopharmacology | volume = 27 | issue = 2 | pages = 248–259 | date = August 2002 | pmid = 12093598 | doi = 10.1016/S0893-133X(02)00304-4 | s2cid = 26101524 | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA, Gonzales R, Kim JH, Alvarez B, Gil R, Laruelle M, Abi-Dargham A | title = Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride | journal = Neuropsychopharmacology | volume = 33 | issue = 13 | pages = 3111–3125 | date = December 2008 | pmid = 18418366 | doi = 10.1038/npp.2008.33 | s2cid = 33993650 | doi-access = free | title-link = doi }}</ref>

Aripiprazole has been characterized as possessing predominantly partial agonist activity on postsynaptic D2 receptors and partial agonist activity on presynaptic D2 receptors;<ref name="pmid17501690" /> however, while this explanation intuitively explains the drug's efficacy as an antipsychotic, as the degree of agonism is a function of more than a drug's inherent properties as well as in vitro demonstration of aripiprazole's partial agonism in cells expressing postsynaptic (D2L) receptors, it was noted that "It is unlikely that the differential actions of aripiprazole as an agonist, antagonist, or partial agonist were entirely due to differences in relative D2 receptor expression since aripiprazole was an antagonist in cells with the highest level of expression (4.6 pmol/mg) and a partial agonist in cells with an intermediate level of expression (0.5–1 pmol/mg).

Instead, the current data are most parsimoniously explained by the "functional selectivity" hypothesis of Lawler et al. (1999)".<ref>{{cite journal | vauthors = Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, Roth BL, Mailman R | title = Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology | journal = Neuropsychopharmacology | volume = 28 | issue = 8 | pages = 1400–1411 | date = August 2003 | pmid = 12784105 | doi = 10.1038/sj.npp.1300203 | s2cid = 22568982 | doi-access = free | title-link = doi }}</ref> Aripiprazole is also a partial agonist of the D3 receptor.<ref name="pmid12784105" /> In healthy human volunteers, D2 and D3 receptor occupancy levels are high, with average levels ranging between approximately 75% at 2 mg/day to approximately 95% at 40 mg/day.<ref name="kegeles" /><ref name="pmid12093598" /> Most atypical antipsychotics bind preferentially to extrastriatal receptors, but aripiprazole appears to be less preferential in this regard, as binding rates are high throughout the brain.<ref name="editorial1">{{cite journal | title = In This Issue | journal = Am J Psychiatry | volume = 165 | issue = 8 | pages = A46 | doi = 10.1176/appi.ajp.2008.165.8.A46 | date = August 2008 }}</ref>

Aripiprazole is also a partial agonist of the postsynaptic serotonin 5-HT1A receptor (intrinsic activity = 68%).<ref name="pmid12784105" /><ref name="pmid12063084" /><ref name="pmid17728427" /> a PET scan study of 12 patients receiving doses ranging from 10 to 30 mg found 5-HT1A receptor occupancy to be only 16% compared to ~90% for D2.<ref name="pmid17728427" /> It is a very weak partial agonist of the Postsynaptic 5-HT2A receptor (intrinsic activity = 12.7%).<ref name="pmid12784105" /> The drug differs from other atypical antipsychotics in having higher affinity for the D2 receptor than for the 5-HT2A receptor.<ref name="pmid17728427" /> At the 5-HT2B receptor, aripiprazole has both great binding affinity and acts as a potent inverse agonist, "Aripiprazole decreased PI hydrolysis from a basal level of 61% down to a low of 30% at 1000 nM, with an EC50 of 11 nM".<ref name="pmid12784105" />

Unlike other antipsychotics, aripiprazole is a high-efficacy partial agonist of the postsynaptic 5-HT2C receptor (intrinsic activity = 82%) this property may underlie the minimal weight gain seen in the course of therapy, however if used while taking antidepressants it will become a functional antagonist and increase weight gain.<ref name="pmid16336943">{{cite journal | vauthors = Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J | title = Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms | journal = Biochemical Pharmacology | volume = 71 | issue = 4 | pages = 521–529 | date = February 2006 | pmid = 16336943 | doi = 10.1016/j.bcp.2005.11.007 }}</ref> At the presynaptic 5-HT7 receptor, aripiprazole is a very weak partial agonist with barely measurable intrinsic activity, and hence is a functional antagonist of this receptor.<ref name="pmid12784105" /><ref name="Davies_2004" /> Aripiprazole also shows lower but likely clinically insignificant affinity for a number of other sites such as the serotonin transporter, while it has negligible affinity for the muscarinic acetylcholine receptors<ref name="pmid12784105" /><ref name="drugLabelPC" />

Since the actions of aripiprazole differ markedly across receptor systems aripiprazole was sometimes an antagonist (e.g., at 5-HT6), sometimes an inverse agonist (e.g., 5-HT2B), sometimes a partial agonist (e.g., D2S, D3S, D4S, D2L). Aripiprazole was frequently found to be a partial agonist or full agonist, with an intrinsic activity that could be low (5-HT2A, 5-HT7), intermediate (D2L, 5-HT1A), or high (5-HT2C). This mixture of agonist actions at D2-dopamine receptors is consistent with the hypothesis that aripiprazole has "functionally selective" actions.<ref>{{cite journal | vauthors = Lawler CP, Prioleau C, Lewis MM, Mak C, Jiang D, Schetz JA, Gonzalez AM, Sibley DR, Mailman RB | title = Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes | journal = Neuropsychopharmacology | volume = 20 | issue = 6 | pages = 612–627 | date = June 1999 | pmid = 10327430 | doi = 10.1016/S0893-133X(98)00099-2 | doi-access = free | title-link = doi }}</ref>

The "functional-selectivity" hypothesis proposes that a mixture of agonist/partial agonist/antagonist actions are likely. According to this hypothesis, agonists may induce structural changes in receptor conformations that are differentially "sensed" by the local complement of G proteins to induce a variety of functional actions depending upon the precise cellular milieu. The diverse actions of aripiprazole at D2-dopamine receptors are clearly cell-type specific (e.g., agonism, antagonism, partial agonism), and are most parsimoniously explained by the "functional selectivity" hypothesis.<ref name="pmid12784105" />

Since 5-HT2C receptors have been implicated in the control of depression, obsessive–compulsive disorder (OCD), and appetite, postsynaptic partial agonism at the 5-HT2C receptor might be associated with therapeutic potential in obsessive–compulsive disorder, obesity, and depression. 5-HT2C agonism has been demonstrated to induce anorexia via enhancement of serotonergic neurotransmission via activation of postsynaptic 5-HT2C receptors; it is conceivable that the 5-HT2C partial agonist actions of aripiprazole may, thus, be partly responsible for the minimal weight gain associated with this compound in clinical trials.

In terms of potential action as an antiobsessional agent, it is worthwhile noting that a variety of 5-HT2A/5-HT2C agonists have shown promise as antiobsessional agents, yet many of these compounds are hallucinogenic. Aripiprazole has a favorable pharmacological profile in being a 5-HT2C partial agonist. Based on this profile, one can predict that aripiprazole may have antiobsessional and anorectic actions in humans.<ref name="pmid12784105" />

Wood and Reavill's (2007) review of published and unpublished data proposed that, at therapeutically relevant doses, aripiprazole may act essentially as a selective partial agonist of the D2 receptor without significantly affecting the majority of serotonin receptors.<ref name="pmid17501690" /> A positron emission tomography imaging study found that 10 to 30 mg/day aripiprazole resulted in 85 to 95% occupancy of the D2 receptor in various brain areas (putamen, caudate, ventral striatum) versus 54 to 60% occupancy of the 5-HT2A receptor and only 16% occupancy of the 5-HT1A receptor.<ref name="pmid26417330">{{cite journal | vauthors = Mauri MC, Paletta S, Maffini M, Colasanti A, Dragogna F, Di Pace C, Altamura AC | title = Clinical pharmacology of atypical antipsychotics: an update | journal = EXCLI Journal | volume = 13 | pages = 1163–1191 | year = 2014 | pmid = 26417330 | pmc = 4464358 }}</ref><ref name="pmid17728427">{{cite journal | vauthors = Mamo D, Graff A, Mizrahi R, Shammi CM, Romeyer F, Kapur S | title = Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study | journal = The American Journal of Psychiatry | volume = 164 | issue = 9 | pages = 1411–1417 | date = September 2007 | pmid = 17728427 | doi = 10.1176/appi.ajp.2007.06091479 }}</ref> It has been suggested that the low occupancy of the 5-HT1A receptor by aripiprazole may have been an erroneous measurement however.<ref name="pmid17728411">{{cite journal | vauthors = Kessler RM | title = Aripiprazole: what is the role of dopamine D(2) receptor partial agonism? | journal = The American Journal of Psychiatry | volume = 164 | issue = 9 | pages = 1310–1312 | date = September 2007 | pmid = 17728411 | doi = 10.1176/appi.ajp.2007.07071043 | s2cid = 1891586 }}</ref>

Aripiprazole acts by modulating neurotransmission overactivity on the dopaminergic mesolimbic pathway, which is thought to be a cause of positive schizophrenia symptoms.<ref name="pmid19909227" /> Due to its partial agonist activity on D2L receptors, aripiprazole may also increase dopaminergic activity to optimal levels in the mesocortical pathways where it is reduced.<ref name="pmid19909227" />

It has also been identified as a potent vesicular monoamine transporter 2 (VMAT2) inhibitor ({{Abbrlink|IC50|half-maximal inhibitory concentration}} = 36{{nbsp}}nM).<ref name="Racz_2025">{{cite journal | vauthors = Racz R, Kozell LB, Eshleman AJ, Bloom SH, Wolfrum KM, Schmachtenberg JL, Swanson TL, Ngai J, Schutzer WE, Janowsky A, Abbas AI, Stavitskaya L | title = Evaluation of the Relationship between Vesicular Monoamine Transporter 2 (VMAT2) Inhibition and Neurologic Adverse Events in Approved Drugs | journal = ACS Pharmacology & Translational Science | date = 22 December 2025 | volume = 9 | issue = 1 | pages = 80–88 | doi = 10.1021/acsptsci.5c00538 | issn = 2575-9108 | doi-access = free | pmid = 41536287 | pmc = 12797167 }}</ref>

=== Pharmacokinetics === Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days. Cmax (maximum plasma concentration) is achieved 3–5 hours after oral dosing. Bioavailability of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and ''N''-dealkylation), principally by the enzymes CYP2D6 and CYP3A4. Its only known active metabolite is dehydro-aripiprazole, which typically accumulates to approximately 40% of the aripiprazole concentration. The parenteral drug is excreted only in traces, and its metabolites, active or not, are excreted via feces and urine.<ref name="drugLabelPC">{{cite web |url=http://www.druglib.com/druginfo/abilify/pharmacology/ |title=Abilify (Aripiprazole) – Clinical Pharmacology |access-date=8 December 2008 |publisher=DrugLib.com |date=14 February 2007 |archive-date=22 May 2008 |archive-url=https://web.archive.org/web/20080522100535/http://www.druglib.com/druginfo/abilify/pharmacology/ }}</ref><ref name="Abilify FDA label" />

== Chemistry == Aripiprazole belongs to the chemical class of drugs called 2,3-dichlorophenylpiperazines and is chemically related to cariprazine, nefazodone, etoperidone, and trazodone.<ref>{{cite book | vauthors = Akritopoulou-Zanze I | veditors = Dinges J, Lamberth C | title = Bioactive heterocyclic compound classes pharmaceuticals | date = 2012 | publisher = Wiley-VCH | location = Weinheim | isbn = 978-3-527-66445-0 | chapter = 6. Arylpiperazine-Based 5-HT1A Receptor Partial Agonists and 5-HT2A Antagonists for the Treatment of Autism, Depression, Anxiety, Psychosis, and Schizophrenia }}</ref><ref>{{cite book | veditors = Dörwald FZ | title = Lead optimization for medicinal chemists: pharmacokinetic properties of functional groups and organic compounds | date = 2012 | publisher = Wiley-VCH | location = Weinheim | isbn = 978-3-527-64564-0 | chapter = 46. Arylalkylamines }}</ref> It is unusual in having twelve known crystalline polymorphs.<ref>{{cite journal |doi=10.1021/acs.cgd.9b01645 |title=Application of the Method of Molecular Voronoi–Dirichlet Polyhedra for Analysis of Noncovalent Interactions in Aripiprazole Polymorphs |year=2020 | vauthors = Serezhkin VN, Savchenkov AV |journal=Crystal Growth & Design |volume=20 |issue=3 |pages=1997–2003 |bibcode=2020CrGrD..20.1997S |s2cid=213824513 }}</ref><ref name=Warren>{{cite journal | vauthors = Warren LR, McGowan E, Renton M, Morrison CA, Funnell NP | title = Direct evidence for distinct colour origins in ROY polymorphs | journal = Chemical Science | volume = 12 | issue = 38 | pages = 12711–12718 | date = October 2021 | pmid = 34703557 | pmc = 8494124 | doi = 10.1039/d1sc04051k }}</ref> Analogues of aripiprazole with higher-efficacy serotonin 5-HT2A receptor partial agonism and with psychedelic- and antidepressant-like effects have been developed.<ref name="LiYanChen2025" />

=== Synthesis === Multiple syntheses of aripiprazole have been reported.<ref>{{cite journal | vauthors = Shi H, Babinski DJ, Ritter T | date = 2015 | title = Modular C-H functionalisation cascade of aryl iodides. | journal = Journal of the American Chemical Society | volume = 137 | issue = 11 | pages = 3775–3778 | doi = 10.1021/jacs.5b01082 | pmid = 25763682 }}</ref><ref>{{cite journal | vauthors = Bonacorsi SJ, Waller SC, Rinehart JK | date = 2006 | title = Synthesis of multi-labeled [14C] aripiprazole | journal = Journal of Labelled Compounds and Radiopharmaceuticals | volume = 49 | issue = 1 | pages = 1–9 | doi = 10.1002/jlcr.1017 }}</ref><ref>{{cite journal | vauthors = Pai NR, Dubhashi DS, Pusalkar D | date = 2010 | title = Substituted 3,4-dihydro-1H-quinolin-2-one derivatives as potential antidepressant, sedative and antiparkinson agents | journal = International Journal of Pharmaceutical Sciences Review and Research | volume = 5 | issue = 2 | pages = 123–131 }}</ref><ref>{{cite journal | vauthors = Kowalki P, Jaskowska J | date = 2012 | title = An Efficient Synthesis of Aripiprazole, Buspirone and NAN-190 by the Reductive Alkylation of Amines Procedure | journal = Archiv der Pharmazie | volume = 345 | issue = 1 | pages = 81–85 | doi = 10.1002/ardp.201100112 | pmid = 22234973 }}</ref><ref>{{cite journal | vauthors = Yang L, Shi L, Xing Q, Huang KW, Xia C, Li F | date = 2018 | title = Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives. ACS Catalysis. State Key Laboratory for Oxo Synthesis and Selective Oxidation | journal = ACS Catalysis | volume = 8 | issue = 11 | pages = 10340–10348 | doi = 10.1021/acscatal.8b02863 }}</ref> A procedure using ethanol as the solvent is shown below.<ref>{{cite journal | vauthors = Dong B, Zheng C, Zhao H, Luo S, Ou Y, Liu C, Chen F | date = 2025 | title = Accelerated flow synthesis of aripiprazole and brexpiprazole in environmentally benign solvents | journal = Green Synthesis and Catalysis | doi = 10.1016/j.gresc.2025.02.001 | doi-access = free }}</ref> Tetrahydroquinoline derivative '''2''' undergoes an SN2 reaction with dihalide '''1''' to give ether '''3'''. This undergoes a further SN2 reaction with piperazine derivative '''4''' giving ariprazole. center|thumb|892x892px|Flow synthesis of aripiprazole.

== History == [[File:Abilify 10mg.jpg|thumb|Abilify (aripiprazole) 10 mg tablets (TR)|alt=]]

Aripiprazole was discovered in 1988 by scientists at the Japanese firm Otsuka Pharmaceutical and was called OPC-14597.<ref name="AdisInsight" /><ref name=NatDD>{{cite journal | vauthors = Grady MA, Gasperoni TL, Kirkpatrick P | title = Aripiprazole | journal = Nature Reviews. Drug Discovery | volume = 2 | issue = 6 | pages = 427–428 | date = June 2003 | pmid = 12790153 | doi = 10.1038/nrd1114 }}</ref><ref>{{cite book |vauthors=Behere PB, Das A, Behere AP |url=https://books.google.com/books?id=i9p1DwAAQBAJ&pg=PA66 |title=Clinical Psychopharmacology: An Update |date=2018 |publisher=Springer |isbn=978-981-13-2092-7 |page=66 |access-date=19 September 2020 |archive-date=4 July 2024 |archive-url=https://web.archive.org/web/20240704193014/https://books.google.com/books?id=i9p1DwAAQBAJ&pg=PA66#v=onepage&q&f=false |url-status=live }}</ref><ref name="Update on the Mechanism of Action o">{{cite journal | vauthors = de Bartolomeis A, Tomasetti C, Iasevoli F | title = Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism | journal = CNS Drugs | volume = 29 | issue = 9 | pages = 773–799 | date = September 2015 | pmid = 26346901 | pmc = 4602118 | doi = 10.1007/s40263-015-0278-3 }}</ref><ref>{{cite web |title=Otsuka's Antipsychotic Abilify Is Approved in Japan, January 23, 2006{{pipe}}News Releases |url=https://www.otsuka.co.jp/en/company/newsreleases/2006/20060125_1.html |access-date=6 October 2022 |website=Otsuka Pharmaceutical Co., Ltd. |archive-date=4 July 2024 |archive-url=https://web.archive.org/web/20240704193016/https://www.otsuka.co.jp/en/company/newsreleases/2006/20060125_1.html |url-status=live }}</ref><ref>{{cite journal | vauthors = Kikuchi T, Maeda K, Suzuki M, Hirose T, Futamura T, McQuade RD | title = Discovery research and development history of the dopamine D2 receptor partial agonists, aripiprazole and brexpiprazole | journal = Neuropsychopharmacology Reports | volume = 41 | issue = 2 | pages = 134–143 | date = June 2021 | pmid = 33960741 | pmc = 8340839 | doi = 10.1002/npr2.12180 }}</ref> It was first published in 1995.<ref name=NatDD /><ref>{{cite journal | vauthors = Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, Morita S | title = 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 274 | issue = 1 | pages = 329–336 | date = July 1995 | doi = 10.1016/S0022-3565(25)10600-9 | pmid = 7616416 }}</ref> Otsuka initially developed the drug, and partnered with Bristol-Myers Squibb (BMS) in 1999 to complete development, obtain approvals, and market aripiprazole.<ref>{{cite news|title=B-MS reveals Ph III aripiprazole data – Pharmaceutical industry news|url=https://www.thepharmaletter.com/article/b-ms-reveals-ph-iii-aripiprazole-data|work=The Pharma Letter|date=17 May 2000|access-date=4 June 2017|archive-date=27 January 2019|archive-url=https://web.archive.org/web/20190127035438/https://www.thepharmaletter.com/article/b-ms-reveals-ph-iii-aripiprazole-data|url-status=live}}</ref>

It was approved by the US Food and Drug Administration (FDA) for schizophrenia in November 2002, and by the European Medicines Agency in June 2004;<ref>{{cite web | title=Abilify Product information | website=Union Register of medicinal products | date=8 June 2004 | url=https://ec.europa.eu/health/documents/community-register/html/h276.htm | access-date=1 October 2023 | archive-date=1 October 2023 | archive-url=https://web.archive.org/web/20231001045647/https://ec.europa.eu/health/documents/community-register/html/h276.htm | url-status=live }}</ref> for acute manic and mixed episodes associated with bipolar disorder on 1 October 2004; as an adjunct for major depressive disorder on 20 November 2007;<ref>{{cite web |url=http://www.webmd.com/depression/news/20071120/fda-oks-abilify-for-depression |title=FDA OKs Abilify for Depression |access-date=8 December 2008 | vauthors = Hitti M |publisher=WebMD |date=20 November 2007| archive-url= https://web.archive.org/web/20081205110249/http://www.webmd.com/depression/news/20071120/fda-oks-abilify-for-depression| archive-date= 5 December 2008 | url-status= live}}</ref> and to treat irritability in children with autism on 20 November 2009.<ref>{{cite web |url=https://www.reuters.com/article/idUSN2023065120091121/ |title=FDA OKs Abilify for child autism irritability |access-date=22 September 2010 |vauthors=Keating G |publisher=Reuters |date=23 November 2009 |archive-date=25 January 2010 |archive-url=https://web.archive.org/web/20100125033718/http://www.reuters.com/article/idUSN2023065120091121 |url-status=live }}</ref> Likewise it was approved for use as a treatment for schizophrenia by the Therapeutic Goods Administration (TGA) of Australia in May 2003.<ref name = Abilify>{{cite web|title=Product Information for Abilify Aripiprazole Tablets & Orally Disintegrating Tablets|website=TGA eBusiness Services|publisher=Bristol-Myers Squibb Australia Pty Ltd|date=1 November 2012|access-date=22 October 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03820-3|archive-date=10 November 2017|archive-url=https://web.archive.org/web/20171110172138/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03820-3|url-status=live}}</ref>

Aripiprazole has been approved by the FDA for the treatment of both acute manic and mixed episodes, in people older than ten years.<ref name="orangeBook" />

In 2006, the FDA required manufacturers to add a black box warning to the label, warning that older people who were given the drug for dementia-related psychosis were at greater risk of death.<ref name=Settle>{{cite news|vauthors=Mitchell M|title=Bristol-Myers Squibb Agrees to $19.5M Settlement Over Abilify Marketing|url=http://www.thelegalintelligencer.com/id=1202774278168/BristolMyers-Squibb-Agrees-to-195M-Settlement-Over-Abilify-Marketing?mcode=0&curindex=0&curpage=ALL|work=The Legal Intelligencer|date=8 December 2016|access-date=4 June 2017|archive-date=27 August 2021|archive-url=https://web.archive.org/web/20210827224129/https://www.law.com/thelegalintelligencer/almID/1202774278168/BristolMyers-Squibb-Agrees-to-195M-Settlement-Over-Abilify-Marketing/?mcode=0&curindex=0&curpage=ALL%2F&slreturn=20210727184129|url-status=live}}</ref>

In 2007, aripiprazole was approved by the FDA for the treatment of unipolar depression when used adjunctively with an antidepressant medication.<ref name="Abilify FDA label" /> That same year, BMS settled a case with the US government in which it paid $515 million; the case covered several drugs but the focus was on BMS's off-label marketing of aripiprazole for children and older people with dementia.<ref>{{cite news|vauthors=Staton T|title=Pharma's Top 11 Marketing Settlements: Bristol-Myers Squibb – Abilify|url=http://www.fiercepharma.com/special-report/bristol-myers-squibb-abilify|access-date=4 June 2017|work=FiercePharma|archive-date=8 June 2017|archive-url=https://web.archive.org/web/20170608185142/http://www.fiercepharma.com/special-report/bristol-myers-squibb-abilify|url-status=live}}</ref>

In 2011 Otsuka and Lundbeck signed a collaboration to develop a depot formulation of aripiprazole.<ref>{{cite web|title=Press Release: Lundbeck and Otsuka Pharmaceutical sign historic agreement to deliver innovative medicines targeting psychiatric disorders worldwide (OMX:LUN)|url=http://investor.lundbeck.com/releasedetail.cfm?releaseid=622993|publisher=Lundbeck|date=11 November 2011|access-date=4 June 2017|archive-url=https://web.archive.org/web/20120401191731/http://investor.lundbeck.com/releasedetail.cfm?ReleaseID=622993|archive-date=1 April 2012}}</ref>

As of 2013, Abilify had annual sales of {{US$|7 billion}}.<ref>{{cite web|url=http://www.medscape.com/viewarticle/820011|title=Top 100 Selling Drugs of 2013|author=Megan Brooks|publisher=Medscape|date=30 January 2014|access-date=15 October 2015|archive-date=31 October 2015|archive-url=https://web.archive.org/web/20151031000635/http://www.medscape.com/viewarticle/820011|url-status=live}}</ref> In 2013 BMS returned marketing rights to Otsuka, but kept manufacturing the drug.<ref>{{cite news|title=BMS cuts salesforce on revised Abilify deal|url=http://www.pmlive.com/pharma_news/bms_cuts_salesforce_on_revised_abilify_deal_447617|work=PM Live|date=7 November 2012|access-date=4 June 2017|archive-date=26 September 2020|archive-url=https://web.archive.org/web/20200926113245/http://www.pmlive.com/pharma_news/bms_cuts_salesforce_on_revised_abilify_deal_447617|url-status=live}}</ref> Also in 2013, Otsuka and Lundbeck received US and European marketing approval for an injectable depot formulation of aripiprazole.<ref>{{cite news |vauthors=Sagonowsky E |title=Lundbeck, Otsuka seek Abilify Maintena nod in bipolar disorder |url=http://www.fiercepharma.com/pharma/lundbeck-otsuka-seek-abilify-maintena-nod-bipolar-disorder |work=FiercePharma |date=1 December 2016 |access-date=4 June 2017 |archive-date=4 August 2020 |archive-url=https://web.archive.org/web/20200804104536/https://www.fiercepharma.com/pharma/lundbeck-otsuka-seek-abilify-maintena-nod-bipolar-disorder |url-status=live }}</ref><ref>{{cite web|title=Abilify Maintena 300mg & 400mg powder and solvent for prolonged-release suspension for injection and suspension for injection in pre filled syringe – Summary of Product Characteristics (SPC)|url=https://www.medicines.org.uk/emc/medicine/31386|publisher=UK Electronic Medicines Compendium|access-date=4 June 2017|archive-date=16 June 2017|archive-url=https://web.archive.org/web/20170616060538/http://www.medicines.org.uk/emc/medicine/31386|url-status=live}}</ref>

Otsuka's US patent on aripiprazole expired on 20 October 2014, but due to a pediatric extension, a generic did not become available until 20 April 2015.<ref name="orangeBook">{{cite web |url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021436&Product_No=001&table1=OB_Rx |title=Patent and Exclusivity Search Results |access-date=8 December 2008 |website=Electronic Orange Book |publisher=U.S. Food and Drug Administration (FDA) |archive-date=4 May 2010 |archive-url=https://web.archive.org/web/20100504180450/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021436&Product_No=001&table1=OB_Rx }}</ref> Barr Laboratories (now Teva Pharmaceuticals) initiated a patent challenge under the Hatch-Waxman Act in March 2007.<ref>{{cite press release| title = Barr Confirms Filing an Application with a Paragraph IV Certification for Abilify Tablets| publisher = Barr Pharmaceuticals, Inc.| date = 20 March 2007| url = http://phx.corporate-ir.net/phoenix.zhtml?c=60908&p=irol-newsArticle&ID=975763&highlight=| access-date = 23 December 2008| archive-date = 16 September 2018| archive-url = https://web.archive.org/web/20180916031606/http://phx.corporate-ir.net/phoenix.zhtml?c=60908&p=irol-newsArticle&ID=975763&highlight=| url-status = live}}</ref> On 15 November 2010, this challenge was rejected by the U.S. District Court in New Jersey.<ref>{{cite news|url=https://www.bloomberg.com/news/2010-11-15/bristol-myers-partner-otsuka-wins-ruling-on-schizophrenia-treatment-patent.html|title=Bristol-Myers Partner Otsuka Wins Abilify Ruling – Bloomberg Business| vauthors = Decker S, Randall T |date=15 November 2010|work=Bloomberg L.P.|access-date=13 May 2015 |archive-url=https://web.archive.org/web/20160722071603/http://www.bloomberg.com/news/articles/2010-11-15/bristol-myers-partner-otsuka-wins-ruling-on-schizophrenia-treatment-patent |archive-date=22 July 2016}}</ref>

Otsuka's European patent EP0367141 which would have expired on 26 October 2009, was extended by a Supplementary Protection Certificate (SPC) to 26 October 2014.,<ref name="EP0367141">{{cite patent | country = EP | number = 0367141 B1 | status = application | title = Carbostyril derivatives | pubdate = 1 October 1996 | fdate = 27 October 1989 | pridate = 13 October 1988 | inventor = Oshiro Y, Sato S, Kurahashi N | assign1 = Otsuka Pharmaceutical Co., Ltd. }}</ref> The UK Intellectual Property Office decided<ref>{{cite web | url = https://www.ipo.gov.uk/p-challenge-decision-results/p-challenge-decision-results-bl?BL_Number=O/098/15 | title = Patent decision | publisher = UK Intellectual Property Office | date = 19 September 2006 | access-date = 7 April 2015 | archive-date = 24 November 2020 | archive-url = https://web.archive.org/web/20201124090605/https://www.ipo.gov.uk/p-challenge-decision-results/p-challenge-decision-results-bl?BL_Number=O%2F098%2F15 | url-status = live }}</ref> on 4 March 2015 that the SPC could not be further extended by six months under Regulation (EC) No 1901/2006. Even if the decision is successfully appealed, protection in Europe will not extend beyond 26 April 2015.

From April 2013 to March 2014, sales of Abilify amounted to almost $6.9 billion.<ref name="thedailybeast.com">{{cite news | url = http://www.thedailybeast.com/articles/2014/11/09/mother-s-little-anti-psychotic-is-worth-6-9-billion-a-year.html | title = Mother's Little Anti-Psychotic Is Worth $6.9 Billion A Year | newspaper = The Daily Beast | date = 9 November 2014 | vauthors = Michaelson J | access-date = 10 November 2014 | archive-date = 18 March 2017 | archive-url = https://web.archive.org/web/20170318134047/http://www.thedailybeast.com/articles/2014/11/09/mother-s-little-anti-psychotic-is-worth-6-9-billion-a-year.html | url-status = live }}</ref>

In April 2015, the FDA announced the first generic versions.<ref>{{cite web|title=FDA approves first generic Abilify to treat mental illnesses|website=U.S. Food and Drug Administration (FDA) |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm444862.htm|access-date=28 April 2015|archive-date=1 May 2015|archive-url=https://web.archive.org/web/20150501034132/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm444862.htm}}</ref><ref>{{cite web|url=https://www.tevapharm.com/news-and-media/latest-news/|title=Latest News {{pipe}} Teva Pharmaceuticals|website=www.tevapharm.com|date=20 May 2023|access-date=24 December 2022|archive-date=24 December 2022|archive-url=https://web.archive.org/web/20221224142618/https://www.tevapharm.com/news-and-media/latest-news/|url-status=live}}</ref> In October 2015, aripiprazole lauroxil, a prodrug of aripiprazole that is administered via intramuscular injection once every four to six weeks for the treatment of schizophrenia, was approved by the FDA.<ref name="pmid26573020">{{cite journal | vauthors = Citrome L | title = Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil | journal = Expert Review of Clinical Pharmacology | volume = 9 | issue = 2 | pages = 169–186 | year = 2015 | pmid = 26573020 | doi = 10.1586/17512433.2016.1121809 | s2cid = 207208248 }}</ref><ref>{{cite web|title=Aristada (aripiprazole lauroxil) FDA Approval History|url=https://www.drugs.com/history/aristada.html|publisher=Drugs.com|access-date=11 May 2018|archive-date=11 May 2018|archive-url=https://web.archive.org/web/20180511214631/https://www.drugs.com/history/aristada.html|url-status=live}}</ref>

In 2016, BMS settled cases with 42 US states that had charged BMS with off-label marketing to older people with dementia; BMS agreed to pay $19.5 million.<ref name=Settle /><ref>{{cite news|vauthors=Staton T|title=Bristol-Myers to pay $19.5 million in Abilify off-label marketing settlement|url=http://www.fiercepharma.com/marketing/bristol-myers-to-pay-19-5-million-abilify-off-label-marketing-settlement|work=FiercePharma|date=14 December 2016|access-date=4 June 2017|archive-date=29 October 2020|archive-url=https://web.archive.org/web/20201029175542/https://www.fiercepharma.com/marketing/bristol-myers-to-pay-19-5-million-abilify-off-label-marketing-settlement|url-status=live}}</ref>

In November 2017, the FDA approved Abilify Mycite, a digital pill containing a sensor intended to record when its consumer takes their medication.<ref name=FDAdigital>{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-pill-sensor-digitally-tracks-if-patients-have-ingested-their-medication|title=FDA approves pill with sensor that digitally tracks if patients have ingested their medication|publisher=U.S. Food and Drug Administration (FDA)|access-date=29 November 2017|archive-date=29 May 2019|archive-url=https://web.archive.org/web/20190529195555/https://www.fda.gov/news-events/press-announcements/fda-approves-pill-sensor-digitally-tracks-if-patients-have-ingested-their-medication}}</ref><ref>{{cite news|url=https://www.nytimes.com/2017/11/13/health/digital-pill-fda.html|title=First Digital Pill Approved to Worries About Biomedical 'Big Brother'|vauthors=Belluck P|date=13 November 2017|work=The New York Times|access-date=29 November 2017|issn=0362-4331|archive-date=28 November 2017|archive-url=https://web.archive.org/web/20171128051922/https://www.nytimes.com/2017/11/13/health/digital-pill-fda.html|url-status=live}}</ref>

A long-acting injectable version of aripiprazole was approved by the FDA for the treatment of bipolar disorder 1 and schizophrenia in April 2023.<ref name="Abilify Asimtufii FDA label">{{cite web | title=Abilify Asimtufii- aripiprazole injection, suspension, extended release | website=DailyMed | date=30 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da4c07fd-1130-4341-bb44-63acfa4162be | access-date=27 December 2024}}</ref><ref>{{cite web | title=Drug Approval Package: Abilify Asimtufii | website=accessdata.fda.gov | date=16 February 2024 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217006Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20240928031757/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217006Orig1s000TOC.cfm | archive-date=28 September 2024 | access-date=27 December 2024}}</ref><ref>{{Cite web |date=28 April 2023 |title=FDA Approves Aripiprazole as First Once-Every-2-Months Long-Acting Injectable for Schizophrenia, Bipolar I Disorder |url=https://www.pharmacytimes.com/view/fda-approves-aripiprazole-as-first-once-every-2-months-long-acting-injectable-for-schizophrenia-bipolar-i-disorder |access-date=16 April 2024 |website=Pharmacy Times |archive-date=30 May 2024 |archive-url=https://web.archive.org/web/20240530142558/https://www.pharmacytimes.com/view/fda-approves-aripiprazole-as-first-once-every-2-months-long-acting-injectable-for-schizophrenia-bipolar-i-disorder |url-status=live }}</ref>

In 2024, the European Commission approved the 2 month long-acting injectable formulation of aripiprazole for the maintenance treatment of schizophrenia.<ref>{{Cite web |date=28 March 2024 |title=Otsuka and Lundbeck's schizophrenia treatment gains EC approval |url=https://www.pharmaceutical-technology.com/news/otsuka-lundbeck-schizophrenia/ |access-date=16 April 2024 |website=Pharmaceutical Technology |archive-date=4 July 2024 |archive-url=https://web.archive.org/web/20240704193017/https://www.pharmaceutical-technology.com/news/otsuka-lundbeck-schizophrenia/ |url-status=live }}</ref> This came after the 1 month long-acting injectable formulation lost drug exclusivity status in the US and Europe (the market is now open to generics).<ref>{{Cite web |date=8 February 2024 |title=Otsuka's Abilify Maintena: dual drug expiry signals sales decline |url=https://www.pharmaceutical-technology.com/analyst-comment/otsukas-abilify-maintena-dual-drug-expiry-signals-sales-decline/?cf-view |access-date=23 February 2025 |website=Pharmaceutical Technology }}</ref>

== Society and culture ==

=== Legal status === {| class="wikitable" |- ! Regulatory administration (country)<ref>Joint Formulary Committee. British National Formulary (BNF) 79. Pharmaceutical Pr; 2020.</ref><ref>{{cite web | title = Australian Medicines Handbook 2013 [Internet] | access-date = 20 September 2013 | url = http://www.psa.org.au/shop/amh | archive-date = 25 September 2013 | archive-url = https://web.archive.org/web/20130925022937/http://www.psa.org.au/shop/amh | url-status = live }}</ref><ref>Truven Health Analytics, Inc. DRUGDEX System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.</ref> !! Schizophrenia !! Acute mania !! Bipolar maintenance !! Major depressive disorder (as an adjunct) !! Irritability in autism |- | Food and Drug Administration (US)<ref name="Abilify FDA label" /> || Yes || Yes || Yes (as an adjunct to lithium/valproate) || Yes || Yes (children and adolescents) |- | Therapeutic Goods Administration (AU) || Yes || Yes (as an adjunct to lithium/valproate) || Yes || No || No |- | Medicines and Healthcare products Regulatory Agency (UK) || Yes || Yes || Yes (to prevent mania) || No || No |- | European Medicines Agency (EU)<ref name="Abilify EPAR" /> || Yes || No || Yes || No || No |}

=== Classification === Aripiprazole has been described as the prototypical third-generation antipsychotic, as opposed to first-generation (typical) antipsychotics like haloperidol and second-generation (atypical) antipsychotics like clozapine.<ref name="pmid28368577">{{cite journal | vauthors = Casey AB, Canal CE | title = Classics in Chemical Neuroscience: Aripiprazole | journal = ACS Chemical Neuroscience | volume = 8 | issue = 6 | pages = 1135–1146 | date = June 2017 | pmid = 28368577 | pmc = 5495458 | doi = 10.1021/acschemneuro.7b00087 }}</ref> It has received this classification due to its partial agonism of dopamine receptors, and is the first of its kind in this regard among antipsychotics, which before aripiprazole acted only as dopamine receptor antagonists.<ref name="pmid28368577" /> The introduction of aripiprazole has led to a paradigm shift from a dopamine antagonist-based approach to a dopamine agonist-based approach for antipsychotic drug development.<ref name="pmid28368577" /><ref name="Update on the Mechanism of Action o"/>

=== Brand names === Brand names of aripiprazole include Abilify, Aristada (as aripiprazole lauroxil), Arip MT, Explemed, Abilify Maintena, Abilify Asimtufii, Arivitae, Abilify MyCite, Opipza, and Mezofy, among others.<ref name="Drugs.com-International">{{cite web | title=Aripiprazole (International database) | website=Drugs.com | date=6 October 2024 | url=https://www.drugs.com/international/aripiprazole.html | access-date=22 October 2024}}</ref><ref>{{Cite web |title=Aripiprazole {{!}} Veterans Affairs |url=http://www.veteranshealthlibrary.va.gov/MedicationsVA/203,a603012 |access-date=2026-01-20 |website=www.veteranshealthlibrary.va.gov |language=en}}</ref>

== Research ==

=== Attention deficit hyperactivity disorder === Aripiprazole was under development for the treatment of attention-deficit hyperactivity disorder (ADHD), but development for this indication was discontinued.<ref name="AdisInsight" /> A 2017 meta review found only preliminary evidence (studies with small sample sizes and methodological problems) for aripiprazole in the treatment of ADHD.<ref name="pmid27993933">{{cite journal | vauthors = De Crescenzo F, Cortese S, Adamo N, Janiri L | title = Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review | journal = Evidence-Based Mental Health | volume = 20 | issue = 1 | pages = 4–11 | date = February 2017 | pmid = 27993933 | doi = 10.1136/eb-2016-102415 | s2cid = 24904076 | doi-access = free | title-link = doi | pmc = 10699262 }}</ref> A 2013 systematic review of aripiprazole for ADHD similarly reported that there is insufficient evidence of effectiveness to support aripiprazole as a treatment for the condition.<ref name="pmid24141455">{{cite journal | vauthors = Ghanizadeh A | title = Systematic review of clinical trials of aripiprazole for treating attention deficit hyperactivity disorder | journal = Neurosciences | volume = 18 | issue = 4 | pages = 323–329 | date = October 2013 | doi = 10.17712/1658-3183.2036 | pmid = 24141455 }}</ref> Although all 6 non-controlled open-label studies in the review reported effectiveness, two small randomized controlled trials found that aripiprazole did not significantly decrease ADHD symptoms.<ref name="pmid24141455" /> A high rate of adverse effects with aripiprazole such as weight gain, sedation, and headache was noted.<ref name="pmid24141455" /> Most research on aripiprazole for ADHD is in children and adolescents.<ref name="pmid24141455" /><ref name="pmid27993933" /> Evidence on aripiprazole specifically for adult ADHD appears to be limited to a single case report.<ref name="pmid26693882">{{cite journal | vauthors = Buoli M, Serati M, Cahn W | title = Alternative pharmacological strategies for adult ADHD treatment: a systematic review | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 2 | pages = 131–144 | date = 2016 | pmid = 26693882 | doi = 10.1586/14737175.2016.1135735 | s2cid = 33004517 }}</ref><ref name="pmid18208634">{{cite journal | vauthors = Kikukawa S | title = Effectiveness of aripiprazole in treatment of adults with attention deficit disorder and restless legs syndrome | journal = The International Journal of Neuropsychopharmacology | volume = 11 | issue = 3 | pages = 439–440 | date = May 2008 | pmid = 18208634 | doi = 10.1017/S1461145707008310 | doi-access = free | title-link = doi }}</ref>

=== Substance dependence === Aripiprazole has been studied for the treatment of amphetamine dependence and other substance use disorders, but more research is needed to support aripiprazole for these potential uses.<ref name="pmid22095579">{{cite journal | vauthors = Brackins T, Brahm NC, Kissack JC | title = Treatments for methamphetamine abuse: a literature review for the clinician | journal = Journal of Pharmacy Practice | volume = 24 | issue = 6 | pages = 541–550 | date = December 2011 | pmid = 22095579 | doi = 10.1177/0897190011426557 | s2cid = 37335642 }}</ref><ref name="pmid23104650">{{cite journal | vauthors = Brunetti M, Di Tizio L, Dezi S, Pozzi G, Grandinetti P, Martinotti G | title = Aripiprazole, alcohol and substance abuse: a review | journal = European Review for Medical and Pharmacological Sciences | volume = 16 | issue = 10 | pages = 1346–1354 | date = October 2012 | pmid = 23104650 }}</ref><ref name="pmid20565449">{{cite journal | vauthors = Karila L, Weinstein A, Aubin HJ, Benyamina A, Reynaud M, Batki SL | title = Pharmacological approaches to methamphetamine dependence: a focused review | journal = British Journal of Clinical Pharmacology | volume = 69 | issue = 6 | pages = 578–592 | date = June 2010 | pmid = 20565449 | pmc = 2883750 | doi = 10.1111/j.1365-2125.2010.03639.x }}</ref><ref name="pmid19042205">{{cite journal | vauthors = Elkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J | title = Pharmacotherapy of methamphetamine addiction: an update | journal = Substance Abuse | volume = 29 | issue = 3 | pages = 31–49 | date = 2008 | pmid = 19042205 | pmc = 2597382 | doi = 10.1080/08897070802218554 | bibcode = 2008JPkR...29...31E }}</ref> Available evidence of aripiprazole for amphetamine dependence is mixed.<ref name="pmid22095579" /><ref name="pmid23104650" /><ref name="pmid20565449" /><ref name="pmid19042205" /> Some studies have reported attenuation of the effects of amphetamines by aripiprazole, whereas other studies have reported both enhancement of the effects of amphetamines and increased use of amphetamines by aripiprazole.<ref name="pmid22095579" /><ref name="pmid23104650" /><ref name="pmid20565449" /><ref name="pmid19042205" /> As such, aripiprazole may not only be ineffective but potentially harmful for treatment of amphetamine dependence, and caution is warranted with regard to its use for such purposes.<ref name="pmid22095579" /><ref name="pmid23104650" /><ref name="pmid20565449" /><ref name="pmid19042205" />

== References == {{Reflist}}

== Further reading == {{refbegin}} * {{cite book | title=Medical Genetics Summaries | chapter=Aripiprazole Therapy and CYP2D6 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK385288/ | 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=2016 | pmid=28520375 | id=Bookshelf ID: NBK385288 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ | access-date=7 February 2020 | archive-date=26 October 2020 | archive-url=https://web.archive.org/web/20201026145821/https://www.ncbi.nlm.nih.gov/books/NBK61999/ | url-status=live }} {{refend}}

== External links == {{Commons category}} * {{cite web | title=Mechanism of Action of Aripiprazole | website=Psychopharmacology Institute | url=https://psychopharmacologyinstitute.com/publication/mechanism-of-action-of-aripiprazole-2119 }}

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