Aripiprazole
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
- Aripiprazole
- Pharmacist Assessment Report
- Aripiprazole: Gaze palsy, familial horizontal, with progressive scoliosis
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Aripiprazole: Gaze palsy, familial horizontal, with progressive scoliosis
One-Sentence Summary
Aripiprazole is an atypical antipsychotic with partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Gaze palsy, familial horizontal, with progressive scoliosis |
| TxGNN Prediction Score | 0.9960 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Aripiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and as an antagonist at 5-HT2A receptors. Detailed mechanism-of-action data were not available in the data compiled for this report, so this description reflects the mechanistic rationale in the evaluation data. This profile allows it to modulate dopaminergic and serotonergic tone alongside an antidepressant, which is the basis for adjunctive use in major depressive disorder.
Mood disorders share disturbances in monoaminergic signalling, so a mechanism that acts on mood-related circuits is plausible across related conditions. Phase 3 randomised trials and several network meta-analyses of adjunctive antipsychotics in depression support this link (for example, a 2026 network meta-analysis in JAMA Psychiatry).
Clinical Trial Evidence
Of the 39 registered trials, the most relevant are listed below (completed Phase 3 trials with direct relevance first).
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00095823 | Phase 3 | Completed | 1200 | 14-week randomised, double-blind, placebo-controlled trial of adjunctive aripiprazole in MDD |
| NCT00095758 | Phase 3 | Completed | 1151 | 14-week randomised, double-blind, placebo-controlled adjunctive trial in MDD |
| NCT01421342 | Phase 3 | Completed | 1522 | VAST-D: aripiprazole augmentation vs bupropion augmentation vs switching in treatment-resistant depression |
| NCT00683852 | Phase 3 | Completed | 225 | Double-blind, placebo-controlled study of reduced-dose adjunctive aripiprazole in MDD |
| NCT00876343 | Phase 3 | Completed | 586 | Placebo-controlled study of adjunctive aripiprazole with an SSRI or SNRI |
| NCT00105196 | Phase 3 | Completed | 349 | 14-week placebo-controlled adjunctive study in MDD with incomplete antidepressant response |
| NCT00095745 | Phase 3 | Completed | 1002 | 52-week open-label safety and tolerability study of adjunctive aripiprazole |
| NCT00882362 | Phase 3 | Completed | 155 | Long-term safety and efficacy of adjunctive aripiprazole with an SSRI or SNRI |
| NCT01111539 | Phase 3 | Terminated | 211 | Aripiprazole/escitalopram combination in MDD; early termination limits interpretation |
| NCT00608543 | Phase 4 | Completed | 17 | Aripiprazole augmentation of SSRI therapy in refractory depression; very small |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42090141 | 2026 | Systematic review / network meta-analysis | JAMA Psychiatry | Adjunctive antipsychotics in MDD; several atypical antipsychotics are FDA-approved on the basis of efficacy and safety evidence |
| 42283956 | 2026 | Network meta-analysis | Advances in Therapy | Compares efficacy and safety of atypical antipsychotics approved as adjunctive MDD treatment |
| 34986373 | 2022 | Systematic review / network meta-analysis | Journal of Affective Disorders | Compares augmentation agents in treatment-resistant depression |
| 39739012 | 2025 | Systematic review / network meta-analysis | Neuropsychopharmacology | Relative effectiveness of antidepressant treatments in treatment-resistant depression |
| 35861202 | 2023 | Systematic review / meta-analysis | Journal of Psychopharmacology | Augmentation and combination treatments for early-stage treatment-resistant depression |
| 34238049 | 2021 | Systematic review / meta-analysis | Journal of Psychopharmacology | Antidepressants plus second-generation antipsychotics vs esketamine vs lithium |
| 38454079 | 2024 | RCT | Molecular Psychiatry | ASCERTAIN-TRD: aripiprazole or rTMS augmentation vs switching to venlafaxine |
| 37149344 | 2023 | Review | Psychiatric Clinics of North America | Antidepressants and atypical antipsychotics for treatment-resistant depression |
| 36855876 | 2023 | Review | American Journal of Psychiatry | Place of antipsychotics in the treatment-resistant depression landscape |
| 25963405 | 2016 | Review | Asia-Pacific Psychiatry | Antipsychotics as adjunctive antidepressants; effective only at sub-antipsychotic doses |
Note: PMID 38669232 (a meta-analysis of aripiprazole or bupropion augmentation) has been retracted and is not relied on here.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10219W | Abilify Maintena | Powder for injection 400 mg (as monohydrate) with diluent | Not recorded in the local data |
Safety Considerations
Safety information from the TGA-approved Product Information was not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for warnings and contraindications.
Drug interactions (100 recorded; examples):
- Major: bupropion
- Moderate: acarbose, famotidine, epinephrine, metformin, pioglitazone, clarithromycin, cimetidine, cisapride, atropine, loperamide
Many of the moderate interactions involve glucose-lowering drugs, anticholinergic agents and CYP-interacting agents. Interaction checking should be part of any prescribing review.
Points raised in the evaluation data:
- Monitor for akathisia, metabolic effects and weight gain.
- Avoid use in patients at risk of impulse-control problems; case reports describe impulsive-compulsive behaviours, including trichotillomania, with aripiprazole.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several large, completed Phase 3 randomised, double-blind, placebo-controlled trials and multiple network meta-analyses directly study adjunctive aripiprazole in major depressive disorder, giving a strong evidence base (L1). Safety information from the local PI is missing, so use should proceed with defined safety monitoring.
To proceed, the following is needed:
- Review of the TGA-approved Product Information for warnings, contraindications and approved indications, as local label data were not available
- Confirmation of the TGA-approved indications for the marketed product, and whether adjunctive MDD use is covered
- A monitoring plan for akathisia, metabolic parameters, weight and impulse-control behaviours
- Detailed mechanism-of-action data from DrugBank
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.