Trihexyphenidyl
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Trihexyphenidyl: From Parkinson Disease to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Trihexyphenidyl is a central anticholinergic drug, originally used to treat Parkinson disease and related movement disorders such as dystonia. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder (ADHD), but there are currently 0 clinical trials and only 1 indirect publication (a case series on tics with dystonia), so the evidence is very weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Parkinson disease and related movement disorders (parkinsonism, dystonia, blepharospasm) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 6 (all cancelled; listed as ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, trihexyphenidyl is a central muscarinic (M1-preferring) anticholinergic. It is used in Parkinson disease and dystonia to correct the cholinergic-dopaminergic imbalance in the striatum.
A similar imbalance in striatal and prefrontal circuits is a plausible but unproven contributor to ADHD symptoms. Tics and movement disorders also often co-occur with ADHD, which may be one reason the model links the two conditions.
However, the link is weak. The only retrieved publication concerns tic disorder with dystonia and does not test trihexyphenidyl in ADHD. The high TxGNN score is a computational prediction only. The anticholinergic burden (cognitive impairment, sedation, attention problems) argues against benefit in ADHD and may even worsen symptoms.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21506147 | 2011 | Cohort / clinical series | Movement Disorders | Large clinical series on primary tic disorder with persistent dystonia, describing prevalence and clinical features. It does not evaluate trihexyphenidyl for ADHD. |
US Market Information
All six US authorizations (ANDAs) are cancelled. No approved indication text is available in the data.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA040254 | Trihexyphenidyl Hydrochloride (Novitium Pharma) | Tablet | Not available |
| ANDA091630 | Trihexyphenidyl Hydrochloride (Natco Pharma) | Tablet | Not available |
| ANDA040251 | Trihexyphenidyl Hydrochloride (Akorn) | Syrup | Not available |
| ANDA040177 | Trihexyphenidyl Hydrochloride (PAI Pharma) | Solution | Not available |
| ANDA084363 | Trihexyphenidyl Hydrochloride (RemedyRepack) | Tablet | Not available |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): The knowledge graph links trihexyphenidyl to caution or contraindication in several conditions, including:
- Eye: angle-closure (closed-angle) glaucoma, open-angle glaucoma
- Urinary and gastrointestinal: benign prostatic hyperplasia, paralytic ileus, achalasia, hiatus hernia, ulcerative colitis, inflammatory bowel disease, Clostridium difficile colitis, necrotizing enterocolitis
- Neuromuscular: myasthenia gravis, neuromuscular junction disease
- Cardiovascular: hypertension, hypotension, coronary artery disease, heart conduction disease, sudden cardiac arrest
- Other: COPD, kidney disease, liver disease, gallbladder disease, gastric ulcer
- Drug Interactions: 100 interactions were identified in total. The data shown include:
- Major: potassium citrate, potassium chloride
- Moderate: other anticholinergics and antimuscarinics (hyoscyamine, atropine, scopolamine, glycopyrronium, dicyclomine, trospium, propantheline, methscopolamine, mepenzolate), opioids and GI-motility drugs (morphine, loperamide, eluxadoline, metoclopramide, prucalopride), cannabinoids (dronabinol, nabilone), pramlintide and magnesium hydroxide
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests almost entirely on a computational score. There are no clinical trials, and the only publication is indirect and does not test the drug in ADHD. The anticholinergic cognitive effects also argue against benefit. In addition, all US licenses are cancelled.
To proceed, the following is needed:
- Detailed mechanism of action data (MOA)
- FDA package insert warnings and contraindications for safety screening
- Preclinical or clinical studies directly testing trihexyphenidyl in ADHD
- An assessment of the cognitive and attention risks from anticholinergic burden, particularly in children
- Clarification of the current US regulatory and marketing status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.