Lisdexamfetamine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Lisdexamfetamine
- Lisdexamfetamine: From Attention Deficit Hyperactivity Disorder to Specific Developmental Disorder
Lisdexamfetamine: From Attention Deficit Hyperactivity Disorder to Specific Developmental Disorder
One-Sentence Summary
Lisdexamfetamine is a prodrug of d-amphetamine, originally used to treat attention deficit hyperactivity disorder (ADHD) and binge eating disorder. The TxGNN model predicts it may be effective for specific developmental disorder, but there are no registered clinical trials and only 2 publications (one case report and one ADHD trial that does not address this new indication). The high prediction score most likely reflects the clinical closeness of this condition to ADHD rather than independent evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Attention deficit hyperactivity disorder; binge eating disorder (Singapore licence text is not available) |
| Predicted New Indication | Specific developmental disorder |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, lisdexamfetamine is an inactive prodrug that is converted in the body to d-amphetamine. d-Amphetamine increases dopamine and norepinephrine signalling, and its efficacy in ADHD has been established. Mechanistically, it may be applicable to attention-related symptoms in other neurodevelopmental conditions.
Specific developmental disorders (for example, learning or attention-related neurodevelopmental conditions) overlap clinically with ADHD. The very high TxGNN score is therefore probably driven by this proximity to the approved indication, not by independent evidence for the new condition.
The one Phase II/III study identified (Japanese paediatric patients, 76 participants aged 6-17 years) concerns ADHD itself, which is an existing indication, and does not demonstrate benefit in a distinct developmental disorder.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31718254 | 2020 | RCT (Phase II/III) | J Child Adolesc Psychopharmacol | Randomised, double-blind, placebo-controlled study of lisdexamfetamine 30, 50 or 70 mg/day for 4 weeks in 76 Japanese children and adolescents with ADHD; the primary endpoint was change in ADHD-RS-IV total score. This is an existing indication, not the predicted one. |
| 37849578 | 2023 | Case report | Cureus | Hao-Fountain syndrome (a rare neurodevelopmental disorder) in an 18-year-old with intellectual disability and ADHD, mimicking fragile X syndrome; it does not assess lisdexamfetamine efficacy. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15840P | VYVANSE CAPSULES 20 mg | Capsule | Not available |
| SIN15841P | VYVANSE CAPSULES 30 mg | Capsule | Not available |
| SIN15842P | VYVANSE CAPSULES 40 mg | Capsule | Not available |
| SIN15843P | VYVANSE CAPSULES 50 mg | Capsule | Not available |
| SIN15844P | VYVANSE CAPSULES 60 mg | Capsule | Not available |
A sixth licence, SIN15845P (70 mg), is also valid. All six are single-ingredient oral capsules, made by Patheon Pharmaceuticals Inc. (bulk production) and Takeda GmbH.
Safety Considerations
- Conditions flagged in the knowledge graph as contraindicated (from the TxGNN knowledge graph, not from label text):
- Cardiovascular: hypertension, coronary artery disease, atherosclerosis, myocardial infarction, stroke and cerebrovascular disorders, sudden cardiac arrest, heart conduction disease
- Psychiatric and neurological: bipolar disorder, psychotic and schizophrenia-spectrum disorders, mental disorders in general, epilepsy, substance-related disorders and dependence
- Other: glaucoma, hyperthyroidism (including Graves disease), hemoglobinopathy, vision disorders
- Drug Interactions: 100 interactions were recorded. Those rated Major among the first 20 listed are:
- Bupropion
- Dolasetron
- Cisapride
- Dexfenfluramine
Many others are rated Moderate (for example epinephrine, clarithromycin, levofloxacin, famotidine, and antacids such as aluminium hydroxide and calcium carbonate).
- Signals from related predictions: case reports link lisdexamfetamine and other stimulants to new-onset trichotillomania, and stimulants are generally cautioned in tic disorders. These do not apply directly to specific developmental disorder, but they show that neuropsychiatric adverse effects need attention in paediatric neurodevelopmental populations.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction has no registered trials and no literature that tests lisdexamfetamine in a specific developmental disorder. The only trial relates to ADHD, which is already an indication. The score seems to reflect clinical overlap with ADHD, and the evidence is at L4 at best.
To proceed, the following is needed:
- A precise definition of which developmental disorder (for example, a learning disorder versus an attention-related condition) is targeted, and how it differs from the existing ADHD indication
- Controlled clinical data in that population
- Detailed mechanism of action data (MOA)
- The Singapore package insert warnings and contraindications, and the approved indication text for the local licences
- A cardiovascular, psychiatric and abuse-liability risk review, especially for paediatric use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.