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Aripiprazole Indications: FDA-Approved and Off-Label Uses

Author: Flavio Guzman, MD. Last updated: November 1, 2016 at 2:06 am

Aripiprazole is a second-generation (atypical) antipsychotic approved for the treatment of schizophrenia, bipolar disorder, depression and autism spectrum disorders.

This article explores FDA-approved indications, dosing and evidence base for common off-label uses.

FDA-approved indications

Aripiprazole was originally approved in 2002 for the treatment of schizophrenia. Currently, the FDA has approved aripiprazole for the treatment of bipolar disorder (mania and mixed episodes and as maintenance treatment), as adjunctive treatment for major depressive disorder (2006) and for autism spectrum disorders (2007).

Below is a list of approved indications and dosing, this information has been extracted from the product prescribing information [1].
For oral formulations (tablet, orally disintegrating tablet and oral solution):

IndicationInitial DoseRecommended DoseMaximum Dose
Schizophrenia
Adults10-15 mg/day10-15 mg/day
30 mg/day
Adolescents2 mg/day10 mg/day30 mg/day
Bipolar Disorder
Treatment of manic or mixed episodes
Bipolar Mania
Adults
Monotherapy
15 mg/day15 mg/day30 mg/day
Bipolar Mania
Adults
Adjunt to lithium or valproate
10-15 mg/day15 mg/day30 mg/day
Bipolar Mania
Pediatric patients
Monotherapy or adjunct to lithium or valproate
2 mg/day10 mg/day30 mg/day
Maintenance treatment
Maintenance treatment of bipolar I disorderDoses not available in product monograph.
Major Depressive Disorder
Adjunct to antidepressants for the treatment of MDD2-5 mg/day5-10 mg/day15 mg/day
Autism Spectrum Disorders
Irritability associated with autistic disorder.
Pediatric patients
2 mg/day5-10 mg/day15 mg/day

For the IM injection:
IndicationInitial DoseMaximum dose
Agitation associated with schizophrenia or bipolar mania.
Adults
9.75 mg/1.3 mL injected IM30 mg/day injected IM

List of selected off-label uses

The table below summarizes the findings of a comparative effectiveness review by the Agency for Healthcare Research and Quality [2].

Most of the uses listed in the table lack of controlled trials, which highlights the need for new studies assessing the evidence for the use of aripiprazole in different clinical conditions.

Off-label UseEvidence
Anxiety
Generalized anxiety disorderNo trials
Social PhobiaNo trials
Attention-deficit hyperactivity disorder
No co-occuring disordersNo trials
Bipolar ChildrenLow or very low evidence of efficacy
Mentally retarded childrenNo trials
Dementia
OverallModerate or high evidence of efficacy
PsychosisLow or very low evidence of efficacy
AgitationLow or very low evidence of efficacy
Depression
MDD monotherapyNo trials
Eating disordersNo trials
InsomniaNo trials
Obsessive-compulsive disorder
Augmentation with SSRINo trials
Augmentation of citalopramNo trials
Personality disorder
Borderline personality disorderLow or very low evidence of efficacy
Schizotypal personality disorderNo trials
Post-traumatic stress disorderNo trials
Substance abuse
AlcoholModerate or high evidence of inefficacy
CocaineNo trials
MethamphetamineLow or very low evidence of inefficacy
Methadone usersNo trials
Tourette's syndromeNo trials

More Information on Off-Label Use

Anxiety disorders

Katzman MA. Aripiprazole: a clinical review of its use for the treatment of anxiety disorders and anxiety as a comorbidity in mental illness. Journal of affective disorders. 2011;128:S11-S20.

” A number of studies have shown atypical antipsychotics to be effective in anxiety, and currently available data suggest that aripiprazole augmentation in patients with anxiety disorders is likely as effective as other atypical antipsychotic drugs.

Although there have been no randomized, controlled trials, aripiprazole has been found to be effective in treating anxiety disorders in two open-label trials.

This combined with the larger data base demonstrating its utility in bipolar disorder and depression, its safety profile and its unique mechanism of action, make aripiprazole for anxiety an intriguing avenue of exploration.”

Dementia

De Deyn PP, Drenth AF, Kremer BP, Oude Voshaar RC, Van Dam D. Aripiprazole in the treatment of Alzheimer’s disease. Expert opinion on pharmacotherapy. 2013(0):1-16

In randomized placebo-controlled clinical trials, aripiprazole shows modest efficacy in the treatment of AD-related psychosis. Neuropsychiatric symptoms alleviated were predominantly psychotic features and agitation. In individual trials, aripiprazole was generally well tolerated, serious side effects were seldom reported and included accidental injury and somnolence. Meta-analyses however demonstrated increased mortality as a class effect for atypical, but also for typical antipsychotics.

No increased cardiovascular outcomes, cerebrovascular accidents, increased appetite or weight gain were demonstrated in meta-analyses for aripiprazole-treated patients with psychosis of dementia. Aripiprazole was found to induce sedation.

Aripiprazole should only be used in selected patient populations resistant to non-pharmacological treatment with persisting or severe psychotic symptoms and/or agitation, and in which symptoms lead to significant morbidity, patient suffering and potential self-harm. The indication for continuing treatment should be revised regularly.

Eating disorders

Trunko ME, Schwartz TA, Duvvuri V, Kaye WH. Aripiprazole in anorexia nervosa and low‐weight bulimia nervosa: Case reports. International Journal of Eating Disorders. 2011;44(3):269-75

There has been much interest in the use of atypical antipsychotics in anorexia nervosa (AN). However, newer, more weight-neutral medications have not been studied in AN, and there are no reports of the use of antipsychotics in bulimia nervosa (BN).

Method

We report on the treatment of eight patients (five with AN and three with BN) with aripiprazole for time periods of four months to more than three years.

Results

All individuals had reduced distress around eating, fewer obsessional thoughts about food, weight and body image, significant lessening of eating-disordered behaviors, and gradual weight restoration where appropriate. Depression, generalized anxiety, and cognitive flexibility improved as well.

Discussion

In summary, these findings support the need to perform controlled trials of aripiprazole in AN and BN.

Related information

References

  1. Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) prescribing information. Retrieved from http://www.abilify.com [retrieval date: February 29, 2013]
  2. Maglione M, Ruelaz Maher A, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ, Ewing BA, Motala A, Perry T. Off-Label Use of Atypical Antipsychotics: An Update. Comparative Effectiveness Review No. 43. Rockville, MD: Agency for Healthcare Research and Quality. September 2011. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm

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PDF: LAI Antipsychotics

Screenshot_2017-01-07_12.39.54

Free PDF Download

  • New formulations (Aristada, Invega Trinza)
  • Practical dosing tables
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