aripiprazole

Aripiprazole is primarily used for the treatment of schizophrenia or bipolar disorder.{{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 }}

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.{{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 }} A 2014 NICE review of the depot formulation of the drug found that it might 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.{{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 }}

A 2014 Cochrane review comparing aripiprazole and other atypical antipsychotics found that it is difficult to determine differences as data quality is poor.{{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 | pages = CD006569 | date = January 2014 | volume = 2014 | pmid = 24385408 | pmc = 4164478 | doi = 10.1002/14651858.CD006569.pub5 }} 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 for the prevention of relapse. A Cochrane review found only low-quality evidence of effectiveness in treating schizophrenia. Accordingly, part of its methodology on quality of evidence is based on the quantity of qualified studies.{{cite web |title= Levels of Evidence |url=https://consumers.cochrane.org/levels-evidence |website=Cochrane.org |access-date=12 September 2019 |archive-date=23 September 2020 |archive-url=https://web.archive.org/web/20200923120907/https://consumers.cochrane.org/levels-evidence |url-status=dead }}

A 2013 review placed aripiprazole in the middle range of 15 antipsychotics for effectiveness, approximately as effective as haloperidol and quetiapine{{Cite journal |date=11 July 2019 |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| vauthors = Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N|volume=394 |issue=10202 |pages=939–951 |doi=10.1016/S0140-6736(19)31135-3 |pmid=31303314 |pmc=6891890 }} and slightly more effective than ziprasidone, chlorpromazine, and asenapine, with better tolerability compared to the other antipsychotic drugs (4th best for reducing weight gain, 5th best for reducing extrapyramidal symptoms, 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.{{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 = The Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}

In 2013 the World Federation of Societies for Biological Psychiatry recommended aripiprazole for the treatment of acute exacerbations of schizophrenia as a Grade 1 recommendation and evidence level A.{{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 }}

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)".{{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 }}

The British Association for Psychopharmacology and the World Federation of Societies for Biological Psychiatry suggest that there is little difference in effectiveness between antipsychotics in the prevention of relapse, and recommend that the specific choice of 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.

Aripiprazole is effective for the treatment of acute manic episodes of bipolar disorder in adults, children, and adolescents.{{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 }}{{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 | pages = CD005000 | date = December 2013 | pmid = 24346956 | doi = 10.1002/14651858.CD005000.pub2 | pmc = 11330668 }} Used as maintenance therapy, it is useful for the prevention of manic episodes but is not useful for bipolar depression.{{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 }}{{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 }} 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.{{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 }} In September 2014, aripiprazole had a UK marketing authorization for up to twelve weeks of treatment for moderate to severe manic episodes in bipolar I disorder in young people aged thirteen and older. Aripiprazole in low doses of 2.5 mg can cause mania in those with Bipolar disorder.{{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 }}{{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 }}{{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 }}

Aripiprazole is an effective add-on treatment for major depressive disorder; however, there is a greater rate of side effects such as weight gain and movement disorders.{{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 | pages = e1001403 | date = March 2013 | pmid = 23554581 | pmc = 3595214 | doi = 10.1371/journal.pmed.1001403 | doi-access = free }}{{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 }}{{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 | pages = CD008121 | date = December 2010 | pmid = 21154393 | doi = 10.1002/14651858.CD008121.pub2 | pmc = 11994262 }} The overall benefit is small to moderate and its use appears to neither improve quality of life nor functioning. 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{{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 }} and it appears lesser interactions with sertraline, escitalopram, citalopram and fluvoxamine. CYP2D6 inhibitors increase aripiprazole concentrations to 2–3 times their normal level. When strong CYP2D6 SSRIs (such as fluoxetine, paroxetine) are co-administered, the FDA recommends dose monitoring, although it is not clear the SSRI dose should be lowered.{{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 | pages = 5 | date = December 2016 | pmid = 27747685 | pmc = 5005780 | doi = 10.1007/s40800-016-0027-7 }}{{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 }}{{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 }}

Short-term data (8 weeks) shows reduced irritability, hyperactivity, inappropriate speech, and stereotypy, but no change in lethargic behaviours.{{cite journal | vauthors = Hirsch LE, Pringsheim T | title = Aripiprazole for autism spectrum disorders (ASD) | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD009043 | date = June 2016 | volume = 2016 | pmid = 27344135 | pmc = 7120220 | doi = 10.1002/14651858.CD009043.pub3 }} Adverse effects include weight gain, sleepiness, drooling, and tremors. 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.

Aripiprazole is approved for the treatment of Tourette syndrome and other tic disorders.{{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 }}{{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 }}{{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 }} It is effective, safe, and well-tolerated for this use per systematic reviews and meta-analyses.{{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 }}{{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 }}{{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 }}{{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 = | pages = 179 | date = July 2015 | pmid = 26220447 | pmc = 4518630 | doi = 10.1186/s12888-015-0504-z | doi-access = free }}

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.{{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 | pages = 317 | date = November 2014 | pmid = 25432131 | pmc = 4262998 | doi = 10.1186/s12888-014-0317-5 | doi-access = free }} The conclusion was based on the results of two relatively small, short-term trials, each of which demonstrated improvements in symptoms.{{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 | pages = 317 | date = November 2014 | pmid = 25432131 | pmc = 4262998 | doi = 10.1186/s12888-014-0317-5 | doi-access = free }}{{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 }}{{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 | pages = 26 | date = December 2008 | pmid = 19105842 | pmc = 2621216 | doi = 10.1186/1744-859X-7-26 | doi-access = free }} However, aripiprazole is cautiously recommended by a 2017 review on antipsychotics for OCD.{{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 | pages = 103 | date = November 2017 | pmid = 29110139 | doi = 10.1007/s11920-017-0847-x | s2cid = 41312623 }} Aripiprazole is not currently approved for the treatment of OCD and is instead used off-label for this indication. Depending on the dose, aripiprazole can increase impulse control issues in a small percentage of people. The FDA Drug Safety Communication warned about this side effect.{{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 |url-status=dead }}

{{See also|Aripiprazole lauroxil}}

Aripiprazole is available in the form of oral tablets, orally disintegrating tablets, oral solutions, oral films, and as injectables for intramuscular administration.{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=accessdata.fda.gov | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | access-date=22 October 2024}}{{failed verification|date=November 2024}} It is also available in the form of aripiprazole lauroxil, a lipophilic ester prodrug of aripiprazole for use as a long-acting injectable.{{failed verification|date=November 2024}}

Contraindications to aripiprazole include known hypersensitivity to aripiprazole, among others.

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

A 2024 study indicated it was found to have the highest hazard ratio among antipsychotics associated with dementia risk: with a hazard ratio of 4.42 (95% confidence interval 1.99-9.81) for all cause dementia;{{cite journal | vauthors = Ma LY, Ou YN, Gao PY, Fu Y, Zhang DD, Yang L, Feng JF, Cheng W, Tan L, Yu JT | display-authors = 6 | title = Associations between antipsychotics exposure and dementia risk: A prospective cohort study of 415,100 participants | journal = Journal of Affective Disorders | volume = 349 | pages = 201–209 | date = March 2024 | pmid = 38199419 | doi = 10.1016/j.jad.2024.01.029 }} the risk appeared to be elevated when the medication was administered in long-acting injectable form compared to oral administration. This elevated risk may be due to the high rate of oral medication non-adherence{{cite journal | vauthors = Acosta FJ, Hernández JL, Pereira J, Herrera J, Rodríguez CJ | title = Medication adherence in schizophrenia | journal = World Journal of Psychiatry | volume = 2 | issue = 5 | pages = 74–82 | date = October 2012 | pmid = 24175171 | pmc = 3782179 | doi = 10.5498/wjp.v2.i5.74 | doi-access = free }} in schizophrenia patients.

In the elderly with dementia, there is an increased risk of death.{{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 }}

In children, adolescents, and young adults, there is an increased risk of suicide.

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.{{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}} Side effects in children are similar, and include sleepiness, increased appetite, and stuffy nose. A strong desire to gamble, binge eat, shop, and engage in sexual activity may also occur rarely.{{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 |url-status=dead }}{{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 }} These urges can be uncontrollable.

Uncontrolled movement such as restlessness, tremors, and muscle rigidity may occur.

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.{{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.}} Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.{{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 }} Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a part of a withdrawal syndrome.{{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 }} It may also result in reoccurrence of the condition that is being treated.{{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=9788847026797 |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 }} Rarely tardive dyskinesia can occur when the medication is stopped.

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 in these people were elevated by up to 3–4 fold over normal therapeutic levels; as of 2008, no deaths had been recorded.{{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 }}{{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 }}

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.{{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}}

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.

Antipsychotics like aripiprazole and stimulant medications, such as amphetamine, are traditionally thought to have opposing effects because both drugs affect dopaminergic neurons. However, both stimulants and antipsychotics lead to increases in synaptic dopamine levels.{{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 }} In antipsychotics, this is caused by the inhibition of dopamine autoreceptors as well as the effects of antipsychotics on non-dopaminergic receptors, while 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.{{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 }}

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

Aripiprazole's mechanism of action is different from those of the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone).{{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 }}{{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}}{{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 }} It shows differential engagement at the dopamine receptor (D₂). Aripiprazole is a partial agonist at dopamine D₂ receptors, a partial agonist at 5-HT_1A receptors, and an antagonist or very weak partial agonist at 5-HT_2A receptors.{{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 }}{{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 }}

It appears to show predominantly partial agonistic activity on postsynaptic D₂ receptors and partial agonist activity on presynaptic D₂ receptors,{{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 }} D₃,{{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 }}{{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 }} and partially D₄ and is a partial activator of serotonin (5-HT_1A,{{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 }} 5-HT_2A, 5-HT_2B, 5-HT₆, and 5-HT₇). It also shows lower effect on histamine (H₁), as well as the serotonin transporter. Aripiprazole acts by modulating neurotransmission overactivity of dopamine, which is thought to mitigate schizophrenia symptoms.{{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 }}

As a pharmacologically unique antipsychotic with pronounced functional selectivity, characterization of this dopamine D₂ partial agonist (with an intrinsic activity of ~50%){{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 }} 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.{{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 }} 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){{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 }}{{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 }} Aripiprazole has been characterized as possessing predominantly partial agonist activity on postsynaptic D₂ receptors and partial agonist activity on presynaptic D₂ receptors; 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 (D_2L) 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)".{{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 }} Aripiprazole is also a partial agonist of the D₃ receptor. 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. 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.{{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 }}

Aripiprazole is also a partial agonist of the postsynaptic serotonin 5-HT_1A receptor (intrinsic activity = 68%). a PET scan study of 12 patients receiving doses ranging from 10 to 30 mg found 5-HT_1A receptor occupancy to be only 16% compared to ~90% for D₂. It is a very weak partial agonist of the Postsynaptic 5-HT_2A receptor (intrinsic activity = 12.7%). The drug differs from other atypical antipsychotics in having higher affinity for the D₂ receptor than for the 5-HT_2A receptor. At the 5-HT_2B 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". Unlike other antipsychotics, aripiprazole is a high-efficacy partial agonist of the postsynaptic 5-HT_2C 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.{{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 }} 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. 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

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-HT_2B), sometimes a partial agonist (e.g., D_2S, D_3S, D_4S, D_2L). Aripiprazole was frequently found to be a partial agonist or full agonist, with an intrinsic activity that could be low (5-HT_2A, 5-HT₇), intermediate (D_2L, 5-HT1A), or high (5-HT_2C). This mixture of agonist actions at D2-dopamine receptors is consistent with the hypothesis that aripiprazole has "functionally selective" actions.{{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 }} 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.

Since 5-HT_2C receptors have been implicated in the control of depression, obsessive–compulsive disorder (OCD), and appetite, postsynaptic partial agonism at the 5-HT_2C receptor might be associated with therapeutic potential in obsessive-compulsive disorder, obesity, and depression. 5-HT_2C agonism has been demonstrated to induce anorexia via enhancement of serotonergic neurotransmission via activation of postsynaptic 5-HT_2C receptors; it is conceivable that the 5-HT_2C 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-HT_2A/5-HT_2C agonists have shown promise as antiobsessional agents, yet many of these compounds are hallucinogenic. Aripiprazole has a favorable pharmacological profile in being a 5-HT_2C partial agonist. Based on this profile, one can predict that aripiprazole may have antiobsessional and anorectic actions in humans.

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. 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-HT_2A receptor and only 16% occupancy of the 5-HT_1A receptor.{{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 }}{{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 }} It has been suggested that the low occupancy of the 5-HT_1A receptor by aripiprazole may have been an erroneous measurement however.{{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 }}

Aripiprazole acts by modulating neurotransmission overactivity on the dopaminergic mesolimbic pathway, which is thought to be a cause of positive schizophrenia symptoms. Due to its partial agonist activity on D_2L receptors, aripiprazole may also increase dopaminergic activity to optimal levels in the mesocortical pathways where it is reduced.

Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days. C_max (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.{{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/ |url-status=dead }}

{{Pharmacokinetics of long-acting injectable antipsychotics}}

Aripiprazole belongs to the chemical class of drugs called 2,3-dichlorophenylpiperazines and is chemically related to cariprazine, nefazodone, etoperidone, and trazodone.{{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 }}{{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 }} It is unusual in having twelve known crystalline polymorphs.{{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 }}{{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 }}

File:Abilify 10mg.jpg)|alt=]]

Aripiprazole was discovered in 1988 by scientists at the Japanese firm Otsuka Pharmaceutical and was called OPC-14597.{{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 }}{{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=9789811320927 |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 }}{{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 }}{{cite web |title=Otsuka's Antipsychotic Abilify Is Approved in Japan, January 23, 2006｜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 }}{{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 }} It was first published in 1995.{{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 }} Otsuka initially developed the drug, and partnered with Bristol-Myers Squibb (BMS) in 1999 to complete development, obtain approvals, and market aripiprazole.{{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}}

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;{{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 }} 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;{{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}} and to treat irritability in children with autism on 20 November 2009.{{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 }} Likewise it was approved for use as a treatment for schizophrenia by the Therapeutic Goods Administration (TGA) of Australia in May 2003.{{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}}

Aripiprazole has been approved by the FDA for the treatment of both acute manic and mixed episodes, in people older than ten years.

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.{{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}}

In 2007, aripiprazole was approved by the FDA for the treatment of unipolar depression when used adjunctively with an antidepressant medication. 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.{{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}}

In 2011 Otsuka and Lundbeck signed a collaboration to develop a depot formulation of aripiprazole.{{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|url-status=dead}}

As of 2013, Abilify had annual sales of {{US$|7 billion}}.{{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}} In 2013 BMS returned marketing rights to Otsuka, but kept manufacturing the drug.{{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}} Also in 2013, Otsuka and Lundbeck received US and European marketing approval for an injectable depot formulation of aripiprazole.{{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 }}{{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}}

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.{{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 |url-status=dead }} Barr Laboratories (now Teva Pharmaceuticals) initiated a patent challenge under the Hatch-Waxman Act in March 2007.{{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}} On 15 November 2010, this challenge was rejected by the U.S. District Court in New Jersey.{{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}}

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.,{{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. }} The UK Intellectual Property Office decided{{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 }} 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.{{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 }}

In April 2015, the FDA announced the first generic versions.{{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|url-status=dead}}{{cite web|url=https://www.tevapharm.com/news-and-media/latest-news/|title=Latest News | 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}} 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.{{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 }}{{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}}

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.{{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}}

In November 2017, the FDA approved Abilify Mycite, a digital pill containing a sensor intended to record when its consumer takes their medication.{{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|url-status=dead}}{{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}}

A long-acting injectable version of aripiprazole was approved by the FDA for the treatment of bipolar disorder 1 and schizophrenia in April 2023.{{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}}{{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 | url-status=dead | archive-date=28 September 2024 | access-date=27 December 2024}}{{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 }}

In 2024, the European Commission approved the 2 month long-acting injectable formulation of aripiprazole for the maintenance treatment of schizophrenia.{{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 }} 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).{{Cite web |date=23 February 2025 |title=Otsuka's Abilify Maintena: dual drug expiry signals sales decline - P… |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=archive.li |archive-date=23 February 2025 |archive-url=https://archive.today/20250223155424/https://www.pharmaceutical-technology.com/analyst-comment/otsukas-abilify-maintena-dual-drug-expiry-signals-sales-decline/?cf-view |url-status=bot: unknown }}

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.{{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 }} 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. 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.

Brand names of aripiprazole include Abilify, Aristada (as aripiprazole lauroxil), Arip MT, Explemed, and Arivitae, among others.{{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}}

Aripiprazole was under development for the treatment of attention-deficit hyperactivity disorder (ADHD), but development for this indication was discontinued. A 2017 meta review found only preliminary evidence (studies with small sample sizes and methodological problems) for aripiprazole in the treatment of ADHD.{{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 }} 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.{{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 | pmid = 24141455 }} 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. A high rate of adverse effects with aripiprazole such as weight gain, sedation, and headache was noted. Most research on aripiprazole for ADHD is in children and adolescents. Evidence on aripiprazole specifically for adult ADHD appears to be limited to a single case report.{{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 }}{{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 }}

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.{{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 }}{{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 }}{{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 }}{{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 }} Available evidence of aripiprazole for amphetamine dependence is mixed. 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. 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.

{{Reflist}}

{{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}}

{{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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Category:Antidepressants

Category:Atypical antipsychotics

Category:Drugs developed by Bristol Myers Squibb

Category:D2 antagonists

Category:D2 receptor agonists

Category:D3 antagonists

Category:D3 receptor agonists

Category:Ethers

Category:H1 receptor antagonists

Category:Mood stabilizers

Category:Otsuka Pharmaceutical

Category:Serotonin-dopamine activity modulators

Category:Tetrahydroquinolines

Category:Treatment of autism

Category:Wikipedia medicine articles ready to translate