Aripiprazole, sold under the brand name Abilify, among others, is an atypical antipsychotic primarily used in the treatment of schizophrenia, mania in bipolar disorder, and irritability associated with autism spectrum disorder; other uses include as an add-on treatment for major depressive disorder, obsessive–compulsive disorder, and tic disorders. Aripiprazole is taken by mouth or via injection into a muscle.
It has generally favorable tolerability. Common side effects include restlessness, insomnia, transient weight gain, nausea, vomiting, constipation, dizziness, and mild sedation. 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 fetus. It is not recommended in women who are breastfeeding. It has not been very well studied in people younger than 18.
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 and has since become available as a generic medication. In 2023, it was the 95th most commonly prescribed medication in the U.S., with more than 7million prescriptions. It is on the World Health Organization's List of Essential Medicines.
Medical uses Aripiprazole is primarily used for the treatment of schizophrenia or bipolar disorder.
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. 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.
A 2014 Cochrane review comparing aripiprazole and other atypical antipsychotics found it 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 in preventing relapse. This review found only low-quality evidence of effectiveness in treating schizophrenia.
A 2013 review placed aripiprazole in the middle range of 15 antipsychotics for effectiveness, approximately as effective as haloperidol and quetiapine 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. 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.
Aripiprazole is recommended as the initial treatment for schizophrenia according to the INTEGRATE consensus international guidelines.
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.
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 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.
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 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 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.
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. The overall benefit is small to moderate and its use appears to improve neither 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 lesser interactions with sertraline, escitalopram, citalopram and fluvoxamine. CYP2D6 inhibitors roughly double aripiprazole concentrations, and dosing is adjusted accordingly, i.e., halved. Some people metabolize CYP2D6 more slowly than most, resulting in about 60% more exposure; in poor metabolizers of CYP2D6 also taking CYP3A4 inhibitors, blood concentrations are roughly tripled. 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.
Autism Short-term data (eight weeks) shows reduced irritability, hyperactivity, inappropriate speech, and stereotypy, but no change in lethargic behaviors. 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 syndrome and other tic disorders. There is evidence supporting that it is effective, safe, and well-tolerated for this use per systematic reviews and meta-analyses.
Developmental stuttering
Off-Label Use and ResearchMechanism: Aripiprazole acts on dopamine pathways, which researchers believe may help regulate the brain circuits involved in speech fluency.Case Reports: Small clinical studies and individual case reports have noted improvements in speech fluency for some adolescents and adults taking specific daily doses (such as 5 mg to 20 mg)
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.
Sleep disorders Studies indicate low-dose aripiprazole (0.5–3mg/day) can be used to treat delayed sleep phase disorder (DSPD), a persistent or recurrent pattern of sleep disturbances that lead to insomnia or excessive daytime sleepiness and impaired functioning in social, occupational, or other spheres.
Available forms
Aripiprazole is available in the form of oral tablets, oral films, oral disintegrating tablets, oral solution, and digital pills with sensors, and as a short-acting injectable for intramuscular administration. It is also available as a long-acting injectable, aripiprazole lauroxil, a lipophilic ester prodrug of aripiprazole designed to be given once per month, and as a once-every-two-months long-acting injectable, under the brand name Abilify Asimtufii.
Contraindications Contraindications to aripiprazole include known hypersensitivity to aripiprazole, among others.
Adverse effects
In elderly people with dementia-related psychosis who are treated with antipsychotics, there is an increased risk of death. In children, adolescents, and young adults treated with antidepressants there is an increased risk of suicidal thoughts or behavior.
In adults, side effects with greater than 10% incidence include weight gain, mania, headache, akathisia, insomnia, delirium, gastrointestinal effects like nausea and constipation, and lightheadedness. Side effects in children are similar, and include sleepiness, increased appetite, and stuffy nose.
In 2016, an FDA Drug Safety Communication warned that aripiprazole can rarely cause impulse control issues. The impulse control problems include a strong desire to gamble, binge eat, shop, and engage in sexual activity. These urges can be uncontrollable. The uncontrollable urges were reported to stop when the dose of aripiprazole was lowered or the medication was discontinued.
Uncontrolled movement such as restlessness, tremors, and muscle rigidity may also occur.
Discontinuation The British National Formulary recommends 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, the primary active metabolite of aripiprazole, in these people were up to four times normal therapeutic levels. no deaths had been recorded.
Interactions