Quetiapine

證據等級: L5

預測適應症: 10 個

Quetiapine: From Schizophrenia/Bipolar Disorder to Retinal Dystrophy with or without Extraocular Anomalies

One-Sentence Summary

Quetiapine is a well-established atypical antipsychotic, globally approved for schizophrenia, bipolar disorder, and as an adjunct therapy for major depressive disorder. The TxGNN model’s top-ranked prediction identifies Retinal Dystrophy with or without Extraocular Anomalies as a potential new indication, however 0 clinical trials and 15 tangentially related publications (none directly studying this drug-disease pair) currently exist, and the mechanistic rationale is absent. Quetiapine is not currently registered in the Philippines market.

Quick Overview

Item	Content
Original Indication	Not registered in Philippines; known global approved uses include schizophrenia, bipolar I/II disorder, and adjunct treatment for major depressive disorder
Predicted New Indication	Retinal Dystrophy with or without Extraocular Anomalies
TxGNN Prediction Score	99.57%
Evidence Level	L5 (Model prediction only — no direct supporting studies)
Philippines Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this Evidence Pack. Based on known pharmacology, Quetiapine is an atypical antipsychotic that primarily antagonises dopamine D2 receptors and serotonin 5-HT2A receptors, with additional binding at histamine H1, adrenergic α1/α2, and muscarinic receptors. These central nervous system receptor interactions underpin its established psychiatric efficacy.

Retinal dystrophy with or without extraocular anomalies is a hereditary retinal degeneration caused by genetic mutations (e.g., RPGR, CRB1, RPGRIP1L) that progressively destroy photoreceptor cells. Its pathophysiology is entirely structural and genetic — not driven by neurotransmitter dysregulation. There is no known mechanistic intersection between Quetiapine’s D2/5-HT2A receptor pharmacology and the photoreceptor degeneration pathways involved in retinal dystrophy.

More critically, existing literature indicates that prolonged use of antipsychotics — including Quetiapine — may cause retinal and lenticular toxicity as an adverse effect (including cataract risk flagged by the EMA). This actively argues against repurposing Quetiapine for any primary ophthalmological indication. The model’s high prediction score most likely reflects a spurious knowledge graph path through shared neurological or syndromic comorbidity nodes rather than a genuine pharmacological signal.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

The 15 retrieved publications are ophthalmology reviews and case series covering general orbital and ocular pathologies. None directly investigate Quetiapine as a therapeutic agent for retinal dystrophy. They are listed below for completeness and transparency:

PMID	Year	Type	Journal	Key Findings
38321238	2024	Review	Pediatric Radiology	Imaging features of pediatric ocular pathologies including congenital/developmental lesions and retinopathies
33447730	2020	Review	Therapeutic Advances in Ophthalmology	Eye involvement in inherited metabolic disorders; covers retinal and optic pathway abnormalities
38249493	2023	Review	Taiwan Journal of Ophthalmology	Congenital anomalies of lens shape and associated anterior segment dysgenesis
33806565	2021	Research Article	Int J Molecular Sciences	Optic nerve and retinal abnormalities in congenital fibrosis of extraocular muscles (KIF21A/TUBB3 mutations)
24932988	2014	Research Article	American Journal of Ophthalmology	Unifying pathogenesis theory for maculopathy associated with cavitary optic disc anomalies
7035111	1981	Case Series	Documenta Ophthalmologica	Wagner-Stickler syndrome complex with vitreoretinal degeneration and sensorineural deafness
30747268	2019	Review	Neuroradiology	Neuroradiological evaluation in acute-onset ophthalmoplegia for differential diagnosis
30196776	2018	Review	J Binocular Vision & Ocular Motility	Congenital cranial dysinnervation disorders (CCDDs) and ophthalmoplegia classification
24413161	2014	Case Report	J Neuro-Ophthalmology	Isolated trochlear-oculomotor synkinesis in congenital cranial dysinnervation disorder
20127583	2010	Clinical Pearls	Seminars in Neurology	Systematic history-taking and examination approach for evaluating diplopia

⚠️ Important: None of these publications study Quetiapine as a treatment for retinal dystrophy. The literature pool reflects general disease-domain content returned by a broad evidence search, not a drug-disease therapeutic relationship.

Philippines Market Information

Quetiapine is currently not registered with the Philippines FDA. No approved products, dosage forms, or indications are on record.

Safety Considerations

Formal Philippines FDA package insert data is not available (no registered product). Based on internationally available safety information for Quetiapine:

Ocular Risk: Long-term use is associated with increased cataract risk (EMA formal warning); this is particularly concerning given the ophthalmological nature of the top predicted indication
Metabolic Effects: Clinically significant risk of weight gain, hyperglycaemia, new-onset diabetes, and dyslipidaemia
Cardiovascular: QTc prolongation risk; postural hypotension
CNS Effects: Sedation, extrapyramidal symptoms, and tardive dyskinesia with prolonged use; neuroleptic malignant syndrome (rare but serious)
Black Box Warning (US FDA): Increased mortality in elderly patients with dementia-related psychosis; suicidality risk in paediatric/young adult populations

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN model assigns a high numerical score (99.57%), but there is no pharmacologically plausible mechanism connecting Quetiapine’s receptor profile to the genetic photoreceptor degeneration pathways underlying retinal dystrophy. The retrieved literature provides zero direct evidence, and the drug’s known ocular adverse effects (cataract risk, potential retinal toxicity) create a net safety concern rather than a therapeutic opportunity for an ophthalmological indication.

To proceed with further research, the following would be required:

A formal mechanistic hypothesis explaining how D2/5-HT2A receptor antagonism could confer neuroprotection or slow degeneration in retinal tissue
At least one preclinical study (animal model or cell-based assay) demonstrating a beneficial effect in a retinal dystrophy model
Comprehensive ocular safety data ruling out retinal or lenticular toxicity in the target patient population
Philippines FDA regulatory pathway assessment for a new indication filing

📌 Alternative Prediction Worth Noting: Trichotillomania (Rank 8)

While the top prediction lacks supporting evidence, Rank 8 — Trichotillomania (Hair-Pulling Disorder) — presents a meaningfully different profile:

Item	Content
TxGNN Score	99.38%
Evidence Level	L4 (case series and pharmacological review)
Decision Stage	S1 — Research Question
Direct Quetiapine Literature	7 publications, including clinical overviews and open-label case studies
Mechanistic Rationale	Biologically plausible: D2 antagonism reduces dopamine-driven compulsive reward; 5-HT2A antagonism aligns with OCD-spectrum augmentation therapy

If resources allow for further exploratory analysis, trichotillomania represents a more scientifically grounded candidate for an off-label Quetiapine repurposing investigation — pending a randomised controlled trial to upgrade the evidence level from L4 to L2/L1.

Disclaimer

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