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
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Other Predicted Indications (Brief Note)
- Disclaimer
Aripiprazole: Gaze palsy, familial horizontal, with progressive scoliosis
One-Sentence Summary
Aripiprazole is an atypical antipsychotic originally used for schizophrenia, bipolar disorder and autism-related conditions. Several large, completed Phase 3 placebo-controlled trials of adjunctive use are included, so the evidence is relatively strong.
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 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From general pharmacology, aripiprazole is a dopamine D2/D3 partial agonist and a 5-HT1A partial agonist with 5-HT2A antagonism. This profile is thought to modulate dopaminergic and serotonergic tone in mesocortical and mesolimbic circuits. This mechanism is drawn from general knowledge, not from the supplied dataset.
Aripiprazole is already used for bipolar disorder, a mood disorder, so the link to depressive disorders is direct. As an add-on to antidepressants, it is proposed to improve response in patients who responded inadequately to antidepressant therapy alone.
The trial and literature record supports this reasoning. Multiple Phase 3 trials test adjunctive aripiprazole in patients with an inadequate antidepressant response, and several network meta-analyses compare it with other augmentation strategies.
Clinical Trial Evidence
The data include 36 trials. The 10 most relevant are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00095823 | Phase 3 | Completed | 1200 | 14-week randomized, double-blind, placebo-controlled study of aripiprazole added to ongoing antidepressant therapy in MDD |
| NCT00095758 | Phase 3 | Completed | 1151 | 14-week randomized, double-blind, placebo-controlled study of adjunctive aripiprazole in MDD |
| NCT01421342 | Phase 3 | Completed | 1522 | VAST-D: aripiprazole augmentation vs bupropion augmentation vs switch to bupropion in Veterans with treatment-resistant MDD |
| NCT00683852 | Phase 3 | Completed | 225 | Double-blind, placebo-controlled study of reduced-dose adjunctive aripiprazole in MDD with inadequate prior response |
| NCT00876343 | Phase 3 | Completed | 586 | Placebo-controlled, double-blind study of aripiprazole adjunctive to SSRI/SNRI in MDD |
| NCT00105196 | Phase 3 | Completed | 349 | 14-week randomized, double-blind, placebo-controlled study of adjunctive aripiprazole in MDD |
| NCT00095745 | Phase 3 | Completed | 1002 | 52-week open-label safety and tolerability study of adjunctive aripiprazole in MDD (safety data only, no controlled efficacy) |
| NCT01111539 | Phase 3 | Terminated | 211 | Aripiprazole/escitalopram combination vs escitalopram in MDD; early termination limits interpretation |
| NCT00080314 | Phase 3 | Completed | 400 | Flexible-dose aripiprazole (5–30 mg) vs placebo in bipolar I depressive episode |
| NCT01488266 | Phase NA | Unknown | 90 | Aripiprazole augmentation vs switching antidepressant class in partially responsive MDD |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42090141 | 2026 | Systematic review / Network meta-analysis | JAMA Psychiatry | Adjunctive antipsychotics in MDD; the FDA has approved 5 atypical antipsychotics in MDD on the basis of efficacy and safety evidence |
| 34986373 | 2022 | Systematic review / Network meta-analysis | J Affect Disord | Compares efficacy and discontinuation of 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 | J Psychopharmacol | Augmentation and combination treatments for early-stage treatment-resistant depression |
| 34238049 | 2021 | Systematic review / Meta-analysis | J Psychopharmacol | Antidepressants plus second-generation antipsychotics vs esketamine vs lithium |
| 38454079 | 2024 | RCT | Mol Psychiatry | ASCERTAIN-TRD: augmentation with aripiprazole or rTMS vs switching to venlafaxine |
| 42283956 | 2026 | Network meta-analysis | Adv Ther | Compares lumateperone with other approved atypical antipsychotics as adjunctive MDD treatment |
| 37149344 | 2023 | Review | Psychiatr Clin North Am | Atypical antipsychotics are the most widely studied augmentation agents in treatment-resistant depression |
| 36855876 | 2023 | Review | Am J Psychiatry | Where antipsychotics fit in the treatment landscape for treatment-resistant depression |
| 25963405 | 2016 | Review | Asia Pac Psychiatry | Aripiprazole, quetiapine and olanzapine have FDA approval as adjuncts to antidepressants; effective only at sub-antipsychotic doses |
Note: one meta-analysis of aripiprazole or bupropion augmentation (PMID 38669232) has been retracted and is not relied on here.
India Market Information
Twenty valid single-ingredient registrations are on record. The registration records contain no approved indication text. Five main registrations are listed.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 99889 | G-Pra 10 Tablet (Gamete Pharma) | Strip of 10 tablets | Not stated in the record |
| 3239 | Arirazo 10mg Tablet (Arinna Lifescience) | Strip of 10 tablets | Not stated in the record |
| 14939 | Aripaxe 20 Tablet (Lifecare Neuro Products) | Strip of 10 tablets | Not stated in the record |
| 2729 | Asprito 10 Tablet (Intas Pharmaceuticals) | Strip of 15 tablets | Not stated in the record |
| 3883 | Aripra 10mg Tablet (Sun Pharmaceutical Industries) | Strip of 10 tablets | Not stated in the record |
Safety Considerations
Contraindications (from knowledge-graph disease associations, not label text): The knowledge graph links aripiprazole to the following conditions, which warrant caution:
- Cardiovascular: orthostatic hypotension, hypotensive disorder, postural orthostatic tachycardia syndrome, multiple system atrophy, myocardial infarction, myocardial ischemia, coronary artery disease, sudden cardiac arrest, heart conduction disease, cerebrovascular disorder
- Metabolic: diabetes mellitus, hyperglycemia, diabetic ketoacidosis, hyperlipidemia, obesity disorder
- Haematological: neutropenia, leukopenia, agranulocytosis, severe congenital neutropenia and related neutropenia syndromes
- Neurological: epilepsy, neuroleptic malignant syndrome
Drug Interactions: 316 interactions were identified. The main ones from the sample reviewed:
- Major: bupropion
- Moderate: antidiabetic agents (acarbose, metformin, pioglitazone, alogliptin, canagliflozin, albiglutide, acetohexamide, chlorpropamide), anticholinergics (atropine, hyoscyamine, clidinium), CYP-inhibiting drugs (cimetidine, clarithromycin, clotrimazole), and others such as epinephrine, famotidine, loperamide, aprepitant and cisapride
Please refer to the package insert for label-based warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 randomized, placebo-controlled trials with over 1,000 participants each, plus several network meta-analyses, support adjunctive aripiprazole in major depressive disorder. Package insert safety information and mechanism data are missing from the compiled data. The knowledge graph also flags numerous cardiometabolic and haematological cautions, and the major interaction with bupropion needs management.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India regulatory source (currently a blocking data gap)
- Mechanism of action data from DrugBank
- Approved indication text for the Indian registrations, to confirm whether the depression indication is already labelled
- A monitoring plan for metabolic, cardiovascular and haematological risks, and a plan for managing interactions (notably bupropion)
Other Predicted Indications (Brief Note)
- Trichotillomania (score 0.9926, evidence level L3, recommendation: research question): two small trials (one open-label, n=12; one not-yet-recruiting placebo-controlled Phase 2, n=100), one open-label study and several case reports. Aripiprazole has also been reported to cause trichotillomania and other impulsive-compulsive behaviours, so the evidence is mixed.
- Asperger syndrome susceptibility and Phelan-McDermid syndrome: no trials or literature. These likely reflect overlap with existing autism-related indications and are model predictions only.
- Other predictions (gaze palsy with progressive scoliosis, amelocerebrohypohidrotic syndrome, distal 17p13.3 microdeletion, Malan overgrowth syndrome, retinal dystrophy, hydranencephaly): no plausible mechanistic link and no clinical evidence. Decision: Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.