Aripiprazole (/ˌɛərɨˈpɪprəzoʊl/ air-i-pip-rə-zohl; brand names: Abilify, Aripiprex) is an atypical antipsychotic. It is recommended and primarily used in the treatment of schizophrenia and bipolar disorder.[5] Other uses include as an add on treatment in major depressive disorder, tic disorders, and irritability associated with autism.[6] According to a Cochrane review, evidence for the effectiveness of the oral form in schizophrenia is not that strong as many people dropped out of the trials of the medication before they were completed.[7]
Side effects include: neuroleptic malignant syndrome, a movement disorder known as tardive dyskinesia and high blood sugar in those with diabetes.[5] In the elderly there is an increased risk of death.[5] It is thus not recommended for use in those with psychosis due to dementia.[5] It is pregnancy category C in the United States and category C in Australia, meaning there is possible evidence of harm.[5][8] It is not recommended in breast feeding.[5] It is unclear if it is safe or effective in people less than 18 years old.[5]
It is a partial dopamine agonist. Aripiprazole was developed by Otsuka in Japan, and in the United States, Otsuka America markets it jointly with Bristol-Myers Squibb. From April 2013 to March 2014, sales of Abilify was almost $6.9 billion.
Medical uses
Aripiprazole is primarily used for the treatment of schizophrenia or bipolar disorder.
Schizophrenia
The United States Food and Drug Administration approved the oral form of aripiprazole for the treatment of acute exacerbations of schizophrenia and for maintenance treatment (relapse prevention) in 2002. The approval was based on efficacy demonstrated in 5 "adequate and well-controlled" clinical trials, including 4 short-term studies ( 4 or 6 weeks) showing a reduction in psychotic symptoms in the acute setting and 1 longer-term study (26 weeks) demonstrating reduced relapse compared to placebo.[10]Marketing approval was granted by the European Medicines Agency based on the results of these same studies, plus an additional long-term study demonstrating non-inferiority to haloperidol in the prevention of relapse.[11] Health Canada approved aripiprazole for the acute and maintenance treatment of schizophrenia in 2009.
A Cochrane review concluded that aripiprazole is similar to other typical and atypical antipsychotics with respect to benefit.[13][14]Compared to typical antipsychotics, there are fewer extrapyramidal side effects, but higher rates of dizziness.[15] With respect to other atypicals, it is difficult to determine differences in adverse effects as data quality is poor.[16] A Lancet review found it is in the middle range of 15 antipsychotics for effectiveness, with better tolerability compared to the other antipsychotic drugs (4th best for weight gain, 5th best for extrapyramidal symptoms, best for prolactin elevation, 2nd best for QTc prolongation, and 5th best for sedation).
A Cochrane review 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. The authors concluded that for acute psychotic episodes aripiprazole results in benefits in some aspects of the condition. The World Federation of Societies for Biological Psychiatry recommends aripiprazole for the treatment of acute exacerbations of schizophrenia as a Grade 1 recommendation and evidence level A.
The National Institute for Health and Care Excellence offers the following recommendations with respect to pharmacological treatment of those presenting with an acute episode of psychosis.
- Offer an oral antipsychotic medication.
- Inform those who want to try psychological interventions alone that these are more effective when performed in conjunction with treatment with an antipsychotic medication
- In the early post-acute period, warn the person of a high risk of relapse if antipsychotic medication is discontinued in the first 1–2 years after the acute episode
- If a decision is made to discontinue medication, reduce the dose gradually and monitor for relapse for at least 2 years.[19]
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 National Institute of Health and Clinical Excellence, 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 persons 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.
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.[26][27][28][29] The overall benefit is small to moderate and its use appears to neither improve quality of life nor functioning.[27] Aripiprazole may interact with some antidepressants, especially SSRIs. There are interactions with fluoxetine and paroxetine and lesser interactions with sertraline, escitalopram, citalopram and fluvoxamine, which inhibit CYP2D6, for which aripiprazole is a substrate. CYP2D6 inhibitors raise aripiprazole concentrations 2-3 times their level.[1]
Autism
Short-term data (8 weeks) shows reduced irritability, hyperactivity, and stereotypy. Adverse effects included weight gain, sleepiness, drooling and tremors. Long-term outcomes are not clear.
Obsessive-compulsive disorder
A 2014 systematic review concluded that add-on therapy with low dose aripiprazole is an effective for obsessive-compulsive disorder that does not improve with SSRIs alone. The conclusion was based on the results of two relatively small, short term trials, each of which demonstrated improvements in symptoms.
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