aripiprazole aripiprazole aripiprazole, sold under the brand names abilify and aristada among others, is an atypical antipsychotic. it is primarily used in the treatment of schizophrenia and bipolar disorder. other uses include as an add-on treatment in major depressive disorder, tic disorders and irritability associated with autism. it is taken by mouth or injection into a muscle. a cochrane review found low-quality evidence of effectiveness in treating schizophrenia. aripiprazoleclinical datapronunciation/ˌɛərɪˈpɪprəzoʊl/air-ih-pip-rə-zohlabilify /əˈbɪlɪfaɪ/ə-bil-if-eye trade namesabilify, aristada, othersahfs/drugs.commonographmedlineplusa603012license data eu ema: by inn us dailymed: aripiprazole us fda: aripiprazole pregnancycategory au: c routes ofadministrationby mouth, intramusculardrug classatypical antipsychoticatc coden05ax12 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only eu: rx-only pharmacokinetic databioavailability87%protein binding>99%metabolismliver (mostly via cyp3a4 and 2d6)elimination half-life75 hours (active metabolite is 94 hours)excretionkidney (27%; <1% unchanged)feces (60%; 18% unchanged)identifiers iupac name 7--3,4-dihydroquinolin-2(1h)-one cas number129722-12-9 ypubchem cid60795iuphar/bps34drugbankdb01238 nchemspider54790 yunii82vfr53i78keggd01164 ychebichebi:31236 ychemblchembl1112 ycomptox dashboard (epa)dtxsid3046083 echa infocard100.112.532 chemical and physical dataformulac23h27cl2n3o2molar mass448.39 g·mol−13d model (jsmol)interactive image smiles clc4cccc(n3ccn(ccccoc2ccc1c(nc(=o)cc1)c2)cc3)c4cl inchi inchi=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) ykey:ceuorzqygodefx-uhfffaoysa-n y ny (what is this?) (verify) in adults, side effects with greater than 10% incidence include weight gain, headache, akathisia, insomnia, and gastro-intestinal effects like nausea and constipation, and lightheadedness. side effects in children are similar, and include sleepiness, increased appetite, and stuffy nose. common side effects include vomiting, constipation, sleepiness, dizziness, weight gain and movement disorders. serious side effects may include neuroleptic malignant syndrome, tardive dyskinesia and anaphylaxis. it is not recommended for older people with dementia-related psychosis due to an increased risk of death. in pregnancy, there is evidence of possible harm to the baby. it is not recommended in women who are breastfeeding. it has not been very well studied in people less than 18 years old. aripiprazole was approved for medical use in the united states in 2002. it is available as a generic medication. in 2020, it was the 89th most commonly prescribed medication in the united states, with more than 8 million prescriptions. medical uses aripiprazole is primarily used for the treatment of schizophrenia or bipolar disorder. schizophrenia the 2016 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. 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. a 2014 cochrane review comparing aripiprazole and other atypical antipsychotics found that it is difficult to determine differences as data quality is poor. 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 quantity of qualified studies. a 2013 review found that it is in the middle range of 15 antipsychotics for effectiveness, approximately as effective as haloperidol and quetiapine 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. 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. 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)". 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 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. bipolar disorder aripiprazole is effective for the treatment of acute manic episodes of bipolar disorder in adults, children, and adolescents. used as maintenance therapy, it is useful for the prevention of manic episodes, but is not useful for bipolar depression. 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. in september 2014, aripiprazole had a united kingdom 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. major depression 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. 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 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 ssri inhibitors are co-administered (e.g., fluoxetine, paroxetine), fda recommends dose monitoring, although it is not clear if ssri dose should be lowered if paroxetine or fluoxetine and aripiprazole are co-administered. autism short-term data (8 weeks) shows reduced irritability, hyperactivity, inappropriate speech, and stereotypy, but no change in lethargic behaviours. 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. tic disorders aripiprazole is approved for the treatment of tourette's syndrome and tic disorders. it is effective, safe, and well-tolerated for this use per systematic reviews and meta-analyses. 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. the conclusion was based on the results of two relatively small, short-term trials, each of which demonstrated improvements in symptoms. however, aripiprazole is cautiously recommended by a 2017 review on antipsychotics for ocd. 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. fda drug safety communication warned about this side effect. adverse effects in adults, side effects with greater than 10% incidence include weight gain, headache, akathisia, insomnia, and gastro-intestinal effects like nausea and constipation, and lightheadedness. 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. uncontrolled movement such as restlessness, tremors, and muscle stiffness may occur. discontinuation the british national formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. 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. it may also result in reoccurrence of the condition that is being treated. rarely tardive dyskinesia can occur when the medication is stopped. 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 in these people were elevated by up to 3–4 fold over normal therapeutic levels; as of 2008 no deaths had been recorded. 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. 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 to their effects on dopamine receptors: stimulants are thought to increase dopamine in the synaptic cleft, whereas antipsychotics are thought to decrease dopamine. however, it is an oversimplification to state the interaction as such, due to the differing actions of antipsychotics and stimulants in different parts of the brain, as well as the effects of antipsychotics on non-dopaminergic receptors. 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. chemistry aripiprazole belongs to the chemical class of drugs called 2,3-dichlorophenylpiperazines and is chemically related to cariprazine, nefazodone, etoperidone, and trazodone. it is unusual in having twelve known crystalline polymorphs. pharmacology pharmacodynamics