Aripiprazole

證據等級: L5

預測適應症: 10 個

ARIPIPRAZOLE: From Antipsychotic Use to Major Affective Disorder (Adjunctive Treatment)

One-Sentence Summary

Aripiprazole is a dopamine D2/D3 partial agonist antipsychotic; this evidence pack does not record its original approved indication (data gap), though real-world monographs list schizophrenia and bipolar I disorder. The TxGNN model predicts it may be effective for Major Affective Disorder (adjunctive treatment of major depressive disorder), with 60+ clinical trials and 20 publications currently supporting this direction, including a completed Phase 3 RCT already establishing this use in real-world practice.

⚠️ Data note: drug.original_indications and taiwan_regulatory.licenses are both empty in this evidence pack, and market_status reads "Not marketed." This conflicts with aripiprazole's well-documented global approval history (Abilify®) and should be verified against source data before this report is used for regulatory decisions.

Quick Overview

Item	Content
Original Indication	[Data Gap] — not populated in evidence pack (`original_indications` empty)
Predicted New Indication	Major Affective Disorder (adjunctive to antidepressant therapy in MDD)
TxGNN Prediction Score	99.62%
Evidence Level	L1
Market Status (this dataset)	Not marketed / 0 authorizations recorded
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this evidence pack (original_moa = [Data Gap]). Based on known pharmacology cited within the repurposing rationale, aripiprazole is a dopamine D2/D3 partial agonist, with additional 5-HT1A partial agonist and 5-HT2A antagonist activity. This receptor profile is the established pharmacological basis for its use as an antidepressant augmentation agent.

The predicted new indication — major affective disorder / major depressive disorder (MDD) — is mechanistically continuous with aripiprazole's known antipsychotic activity: partial dopaminergic and serotonergic modulation is theorized to correct monoaminergic dysregulation implicated in treatment-resistant depression. In fact, aripiprazole augmentation of antidepressants has already received regulatory approval and extensive clinical validation outside of this dataset (e.g., FDA approval as an adjunct for MDD), which is consistent with — and substantially strengthens — the TxGNN prediction.

The evidence pack itself flags an important caveat: because original_indications and licenses are empty, the internal consistency between "original indication" and "predicted indication" cannot be verified from this dataset alone. The mechanistic rationale should therefore be read as corroborated by external knowledge, not by this evidence pack's regulatory fields.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00683852	Phase 3	Completed	225	Pivotal double-blind, placebo-controlled trial of reduced-dose aripiprazole adjunctive to antidepressant therapy in MDD with inadequate response to prior treatment
NCT00876343	Phase 3	Completed	586	Placebo-controlled, parallel-group study of aripiprazole adjunctive to SSRI/SNRI in MDD
NCT00105196	Phase 3	Completed	349	14-week randomized, double-blind, placebo-controlled adjunctive trial in MDD with incomplete response to open-label antidepressant
NCT02046564	Phase 3	Completed	412	ASC-01 (aripiprazole/sertraline combination) vs sertraline monotherapy in MDD with incomplete response
NCT01567527	Phase 3	Completed	731	52-week placebo-controlled study of IM depot aripiprazole as maintenance therapy in bipolar I disorder
NCT01284218	N/A	Completed	23,514	Retrospective real-world database study of health care utilization/costs with adjunctive aripiprazole vs other augmentation therapies in MDD
NCT01429831	Phase 4	Completed	300	Taiwan real-world observational study of aripiprazole augmentation effectiveness/tolerability in MDD inadequate responders
NCT00953745	N/A	Completed	43	PET/fMRI mechanistic study testing dopaminergic pathway hypothesis for aripiprazole augmentation in treatment-resistant depression
NCT00873795	N/A	Completed	41	Small comparative trial of low-dose aripiprazole + sertraline vs sertraline alone in fresh MDD
NCT05473741	N/A	Completed	51	Longitudinal cohort on breakthrough symptom risk in remitted patients on long-acting antipsychotic maintenance therapy

Literature Evidence

PMID	Year	Type	Journal	Key Findings
38669232	2024	RCT meta-analysis	PLoS One	Largest systematic review/meta-analysis of RCTs on aripiprazole or bupropion augmentation and switching in treatment-resistant depression/MDD
34986373	2022	Network meta-analysis	J Affect Disord	Compares efficacy and discontinuation of augmentation agents (incl. aripiprazole) in treatment-resistant depression
36961650	2023	RCT	CNS Drugs	Pivotal safety/tolerability/PK study of aripiprazole 2-month long-acting injectable in schizophrenia and bipolar I disorder
38219278	2024	Systematic review	Neuropsychopharmacol Rep	Network meta-analysis comparing brexpiprazole, aripiprazole, and placebo for MDD in Japanese patients
36239033	2023	RCT	J Psychopharmacol	Randomized, double-blind, placebo-controlled trial of aripiprazole adjunctive therapy in MDD with somatic symptoms (with EEG evidence)
34167174	2021	Systematic review/meta-analysis	Prim Care Companion CNS Disord	Long-term efficacy and tolerability of adjunctive aripiprazole for MDD
35510505	2023	Systematic review/meta-analysis	Psychol Med	Efficacy and safety/tolerability of antipsychotics (monotherapy and adjunctive) in adult MDD
37149344	2023	Review	Psychiatr Clin North Am	Review of pharmacotherapy for treatment-resistant depression: antidepressants and atypical antipsychotics, including aripiprazole
36855876	2023	Review	Am J Psychiatry	Review of antipsychotic pharmacotherapies for treatment-resistant depression within the evolving therapeutic landscape
21254788	2011	Review	CNS Drugs	Overview and clinical trial data implications for aripiprazole as adjunctive therapy in MDD

Germany Market Information

No marketing authorizations were found in this evidence pack (taiwan_regulatory.total_licenses = 0, licenses = [], market_status = "Not marketed"). This is inconsistent with aripiprazole's known global regulatory history and should be treated as a data gap requiring source verification rather than a factual statement about market absence.

Safety Considerations

Please refer to the package insert for safety information. (key_warnings, contraindications, and ddi are all unpopulated / [Data Gap] in this evidence pack.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The predicted indication is backed by L1-level evidence — a completed Phase 3 RCT (NCT00683852) plus multiple additional completed Phase 3 trials, a large real-world database study (n=23,514), and several RCT-level meta-analyses — and is directionally consistent with aripiprazole's well-established real-world use as antidepressant augmentation. However, critical drug-level fields (MOA, safety warnings, contraindications, DDI, market authorizations, original indication) are all data gaps in this pack, which blocks a full S1 safety pre-assessment.

To proceed, the following is needed:

TFDA/regulatory label (仿單) warnings and contraindications (currently Blocking data gap, DG001)
Verified drug-level MOA from DrugBank (DG002)
Reconciliation of original_indications / market_status / licenses fields against known real-world approval status for aripiprazole
Drug interaction (DDI) profile, particularly for antidepressant/antipsychotic combination use in MDD augmentation
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.