Aripiprazole
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Aripiprazole: From Its Labeled Psychiatric Uses to Major Affective Disorder
One-Sentence Summary
Aripiprazole is an atypical antipsychotic marketed in the US as ABILIFY and as many generics. The TxGNN model predicts it may be effective for major affective disorder (major depression and bipolar-spectrum mood disorders), with 50 registered clinical trials and 20 publications retrieved for this direction. Caveat: adjunctive use in major depression and use in bipolar disorder are already established labeled uses in the US, so this is closer to confirming an existing indication than to true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Major affective disorder |
| TxGNN Prediction Score | 99.62% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Aripiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors. Detailed mechanism-of-action text was not supplied in the source record, so this profile comes from the mechanistic rationale and the literature. It plausibly explains its role as an add-on to antidepressants in treatment-resistant depression, and its use in bipolar disorder.
The US license records supplied here carry no approved-indication text. The original labeled uses therefore could not be read directly from the record and should be checked against the current label. Even so, the clinical record is consistent with the prediction. Several completed Phase 3 placebo-controlled trials tested aripiprazole added to an antidepressant in patients with inadequate response. Multiple systematic reviews and meta-analyses also cover this use.
Because adjunctive MDD and bipolar use are already labeled in the US, the value of this report is mainly as confirmation and as a guide to safe use. It is not a new-indication discovery.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00683852 | Phase 3 | Completed | 225 | Double-blind, placebo-controlled; reduced-dose aripiprazole added to antidepressant in MDD with inadequate response |
| NCT00095823 | Phase 3 | Completed | 1200 | 14-week randomized, double-blind, placebo-controlled adjunctive therapy in MDD |
| NCT00095758 | Phase 3 | Completed | 1200 | 14-week randomized, double-blind, placebo-controlled adjunctive therapy in MDD |
| NCT00105196 | Phase 3 | Completed | 349 | 14-week double-blind, placebo-controlled adjunct after incomplete response to an 8-week antidepressant trial |
| NCT00876343 | Phase 3 | Completed | 586 | Placebo-controlled adjunct to SSRI/SNRI in MDD (Japan) |
| NCT02046564 | Phase 3 | Completed | 412 | ASC-01 (aripiprazole/sertraline) vs sertraline alone in patients with incomplete response to sertraline |
| NCT00095745 | Phase 3 | Completed | 1002 | 52-week open-label safety and tolerability of adjunctive aripiprazole in MDD |
| NCT01111539 | Phase 3 | Terminated | 211 | Aripiprazole/escitalopram combination in MDD with incomplete response; stopped early |
| NCT00080314 | Phase 3 | Completed | 400 | Flexible-dose aripiprazole vs placebo in bipolar I disorder with a major depressive episode |
| NCT07153406 | Phase 3 | Not yet recruiting | 220 | Esketamine vs aripiprazole (both with SSRI/SNRI) in elderly treatment-resistant MDD; aripiprazole is the comparator |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38669232 | 2024 | Meta-analysis of RCTs | PLoS One | Efficacy and safety of aripiprazole or bupropion augmentation and switching in TRD/MDD |
| 34986373 | 2022 | Systematic review / NMA | J Affect Disord | Compared augmentation agents in treatment-resistant depression for efficacy and discontinuation |
| 38219278 | 2024 | Systematic review / NMA | Neuropsychopharmacol Rep | Brexpiprazole vs aripiprazole vs placebo in Japanese MDD with inadequate antidepressant response |
| 35510505 | 2023 | Systematic review / meta-analysis | Psychol Med | Efficacy and safety of antipsychotics as monotherapy and adjunct in adult MDD |
| 34167174 | 2021 | Systematic review / meta-analysis | Prim Care Companion CNS Disord | Long-term (≥6 months) efficacy and tolerability of adjunctive aripiprazole in MDD |
| 34238049 | 2021 | Meta-analysis | J Psychopharmacol | Antidepressant plus second-generation antipsychotic vs esketamine vs lithium combinations |
| 36239033 | 2023 | RCT | J Psychopharmacol | Adjunctive aripiprazole in MDD with somatic symptoms, with clinical and EEG evidence |
| 37149344 | 2023 | Review | Psychiatr Clin North Am | Atypical antipsychotics are the most widely studied augmentation agents in TRD; aripiprazole is among them |
| 36855876 | 2023 | Review | Am J Psychiatry | Where antipsychotics fit among current TRD pharmacotherapies |
| 21254788 | 2011 | Review | CNS Drugs | Overview of the clinical trial program for adjunctive aripiprazole in MDD |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA 021436 | ABILIFY | Tablet | Not provided in the source record |
| NDA 207202 | Abilify MyCite | Tablet with sensor | Not provided in the source record |
| ANDA 207105 | Aripiprazole (Ascend Laboratories) | Tablet | Not provided in the source record |
| ANDA 205064 | Aripiprazole (XLCare Pharmaceuticals) | Tablet | Not provided in the source record |
| ANDA 204838 | Aripiprazole (Amneal Pharmaceuticals) | Tablet | Not provided in the source record |
The record lists 20 licenses in total. An oral soluble film is also on the market.
Safety Considerations
- Drug Interactions: The interaction query returned no results.
Warnings and contraindications were not available in the source record. Please refer to the package insert for full safety information.
Guardrails from the mechanistic rationale: use only within labeled indications, and monitor for akathisia, metabolic effects, and impulse-control adverse events.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed, large Phase 3 placebo-controlled trials and several meta-analyses support adjunctive aripiprazole in major depression. That is enough for Evidence Level L1. However, this use is already labeled in the US, so the finding confirms an existing indication rather than a new one.
To proceed, the following is needed:
- Verify the approved indications against the current US package insert, because the license records carry no indication text.
- Obtain the label’s warnings and contraindications, which were not available in the source record.
- Set a monitoring plan for akathisia, metabolic parameters, and impulse-control behaviors.
The other nine predicted indications are much weaker, and this report does not cover them in detail.
- Trichotillomania has case reports, a small open-label trial, and a not-yet-recruiting Phase 2 RCT. It is a research question only, and aripiprazole has also been reported to induce impulsive-compulsive behaviors.
- Asperger syndrome (susceptibility) and Phelan-McDermid syndrome have no trial or literature evidence, only indirect plausibility through autism-spectrum features.
- The remaining six predictions are prediction-only with no supporting evidence, and should be held.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.