Donepezil
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Donepezil: From Alzheimer Disease to Psychogenic Movement Disorders
One-Sentence Summary
Donepezil is an acetylcholinesterase inhibitor originally used to treat Alzheimer disease. The TxGNN model predicts it may be effective for psychogenic movement disorders, but no clinical trials and no publications currently support this specific prediction. The next-ranked prediction, chronic tic disorder, has more support (5 publications, no registered trials), and is discussed below as a more tractable research direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Alzheimer disease (the approved-indication text is blank on the local licences; this is taken from the knowledge-graph indication list) |
| Predicted New Indication | Psychogenic movement disorders |
| TxGNN Prediction Score | 99.23% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 13 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this report. Based on known information, donepezil is a cholinesterase inhibitor, and its efficacy in Alzheimer disease is established. Mechanistically, raising cholinergic tone may influence motor-control circuits in the basal ganglia.
A cholinergic mechanism is plausible for movement disorders in general. However, there is no direct rationale for psychogenic movement disorders, which are functional rather than degenerative conditions. The prediction rests on the model score alone.
Other predicted indications (for context):
| Rank | Predicted Indication | Score | Evidence Level | Assessment |
|---|---|---|---|---|
| 2 | Chronic tic disorder | 99.19% | L3 (provisional) | Research Question. Small clinical reports and mouse work support a cholinergic role in tics. |
| 4 | Extrapyramidal and movement disease | 99.16% | L4 | Research Question. A 2025 systematic review also flags a safety signal, as cholinesterase inhibitors can worsen parkinsonism or tremor. |
| 8 | Lingual-facial-buccal dyskinesia (tardive dyskinesia) | 99.02% | L3 | Research Question. Cochrane reviews of cholinergic drugs exist, but they do not establish clear efficacy for donepezil. |
| 10 | Glaucoma | 98.28% | L4 | Hold. Evidence is mixed, and there are safety signals. |
| 3, 5, 6, 7, 9 | Primary orthostatic tremor, benign shuddering attacks, tremor-nystagmus-duodenal ulcer syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, acute intermittent porphyria | 98.7%–99.2% | L5 | Hold. Prediction only, with no supporting evidence. |
Clinical Trial Evidence
Currently no related clinical trials registered for psychogenic movement disorders (nor for any of the other top-ranked predicted indications).
Literature Evidence
Currently no related literature available for psychogenic movement disorders.
For reference, the most relevant publications for the second-ranked prediction (chronic tic disorder) are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18343255 | 2008 | Clinical study (likely open-label, design to be verified) | Clinical Therapeutics | 18-week dose-escalating study of donepezil in children and adolescents with tics and ADHD, based on the idea that striatal cholinergic dysfunction contributes to both |
| 10440471 | 1999 | Case report | J Clin Psychopharmacol | Donepezil for Tourette's disorder and ADHD |
| 16986157 | 2006 | Commentary | Mov Disord | Discussion of donepezil's possible effectiveness in Tourette's syndrome |
| 16045972 | 2005 | Preclinical (mouse) | Pharmacol Biochem Behav | Donepezil, nicotine and haloperidol effects on serotonergic tic-like behaviour in mice |
| 14643839 | 2003 | Preclinical (mouse) | Pharmacol Biochem Behav | Donepezil reduced DOI-induced head twitches, a model of tics |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13645P | Aricept Evess 5mg orodispersible tablet | Orally disintegrating tablet | Not stated in the data |
| SIN13646P | Aricept Evess 10mg orodispersible tablet | Orally disintegrating tablet | Not stated in the data |
| SIN14575P | Aricept Film-coated Tablets 23mg | Film-coated tablet | Not stated in the data |
| SIN15565P | Jubdozil Film Coated Tablet 5mg | Film-coated tablet | Not stated in the data |
| SIN16006P | Alzer 10 Donepezil Hydrochloride Tablets USP 10 mg | Film-coated tablet | Not stated in the data |
There are 13 valid single-ingredient registrations in total, all oral, with no cancelled licences. No topical or injectable forms are registered.
Safety Considerations
Knowledge-graph contraindication signals (from the knowledge graph, not from label text): epilepsy, asthma (including intrinsic and allergic asthma), bladder neck obstruction, active peptic ulcer disease, sick sinus syndrome (including the familial form), and atrioventricular block.
Drug Interactions: 100 interactions were identified, of which 20 are listed in the data compiled for this report. The most notable:
- Major: Bupropion
- Moderate: anticholinergic agents (atropine, hyoscyamine, glycopyrronium, clidinium, dicyclomine), acid suppressants (famotidine, ranitidine, cimetidine), loperamide, dexamethasone, metronidazole, dolasetron, and bowel-preparation agents (picosulfuric acid, polyethylene glycol with electrolytes)
- Minor: aprepitant, acetylsalicylic acid, lorcaserin, clarithromycin
Indication-specific signals from the literature:
- A 2025 systematic review reports that cholinesterase inhibitors can be associated with movement disorders (including worsened parkinsonism or tremor), which is directly relevant to any movement-disorder use.
- Case reports describe donepezil-associated Pisa syndrome and jaw tremor.
- A case report describes angle-closure glaucoma after donepezil was stopped.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The psychogenic movement disorders prediction rests on a high model score alone, with no trials, no literature, and no mechanistic support specific to the condition. Donepezil is well established and widely registered in Singapore, but that does not support this new use. The literature also shows donepezil can cause or worsen some movement disorders.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are a blocking gap for safety screening
- Mechanism of action data for donepezil
- A targeted literature search on cholinergic mechanisms in functional or psychogenic movement disorders
- If a movement-disorder direction is pursued, consider chronic tic disorder first. It has the strongest direct clinical signal (a pediatric open-label study and case reports), but the study designs should be verified and a controlled trial would be needed.
- A safety review of donepezil in patients with movement disorders, given the reported tremor, dystonia, and parkinsonism signals
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.