Donepezil
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Donepezil: Psychogenic movement disorders
One-Sentence Summary
Donepezil is a cholinesterase inhibitor originally used to treat Alzheimer’s disease. The TxGNN model predicts it may be effective for chronic tic disorder (the highest-ranked prediction with any supporting literature), with 0 registered clinical trials and 5 publications, mostly small, open-label, case-report or preclinical studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Psychogenic movement disorders |
| TxGNN Prediction Score | 0.9923 |
| Evidence Level | L5 (L5 for the rank 1 prediction) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (chronic tic disorder is a research question only) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, donepezil is a cholinesterase inhibitor with an established role in Alzheimer’s disease, and it may be mechanistically applicable to tic disorders.
Striatal cholinergic dysfunction has been proposed in tics and ADHD. Cholinergic and nicotinic modulation of dopaminergic and serotonergic pathways in the striatum could reduce tics. Mouse studies support this: donepezil reduced the DOI-induced head twitch response, a model of tic-like behaviour. Small clinical reports in children and adolescents with tics and ADHD point in the same direction.
This link is plausible but unproven. No controlled trials were retrieved, and the human data are limited to an open-label study and case reports.
Other predictions were reviewed (see the table below). Most have no evidence, and the evidence for the rest is indirect or conflicting.
| Rank | Predicted Indication | Score | Evidence Level | Comment |
|---|---|---|---|---|
| 1 | Psychogenic movement disorders | 0.9923 | L5 | No trials or literature |
| 2 | Chronic tic disorder | 0.9919 | L5 | Small open-label study, case reports, mouse data |
| 3 | Primary orthostatic tremor | 0.9917 | L5 | No evidence |
| 4 | Extrapyramidal and movement disease | 0.9916 | L5 | Small benefit study in tardive disorders, but a 2025 systematic review links cholinesterase inhibitors to movement disorders |
| 5 | Benign shuddering attacks | 0.9916 | L5 | No evidence; benign paediatric condition |
| 6 | Tremor-nystagmus-duodenal ulcer syndrome | 0.9915 | L5 | Only article is off-target; ulcer safety concern |
| 7 | Benign paroxysmal tonic upgaze of childhood with ataxia | 0.9912 | L5 | No evidence |
| 8 | Lingual-facial-buccal dyskinesia | 0.9902 | L5 | Cochrane reviews of cholinergic drugs in tardive dyskinesia; donepezil-specific efficacy unclear |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Literature for the chronic tic disorder prediction (rank 2):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18343255 | 2008 | Open-label study | Clinical Therapeutics | 18-week, single-centre, dose-escalating, prospective open-label study of donepezil in children and adolescents with tics and ADHD. The abstract available notes striatal cholinergic dysfunction as the rationale. |
| 10440471 | 1999 | Case report | J Clin Psychopharmacol | Donepezil used in Tourette’s disorder and ADHD |
| 16986157 | 2006 | Commentary/case report | Movement Disorders | Asks whether donepezil is also effective in Tourette’s syndrome |
| 16045972 | 2005 | Preclinical (mouse) | Pharmacol Biochem Behav | Donepezil and nicotine attenuated DOI-induced head twitch response, a model of tics; interaction with haloperidol examined |
| 14643839 | 2003 | Preclinical (mouse) | Pharmacol Biochem Behav | Donepezil affected DOI-induced head twitches in mice, suggesting relevance to Tourette syndrome |
Selected literature for other predictions:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29553158 | 2018 | Cochrane systematic review | Cochrane Database Syst Rev | Cholinergic medication for antipsychotic-induced tardive dyskinesia (lingual-facial-buccal dyskinesia); donepezil-specific benefit not clear from retrieved data |
| 40224553 | 2025 | Systematic review | Brain Circulation | Movement disorders associated with acetylcholinesterase inhibitors in Alzheimer’s dementia (safety signal) |
| 15669896 | 2005 | Clinical study | J Clin Psychiatry | Reported benefit of donepezil in elderly patients with tardive movement disorders |
| 20415624 | 2010 | Pilot study | J Ocul Pharmacol Ther | Effects of donepezil on cerebral and optic nerve head blood flow and visual field in normal-tension glaucoma |
| 16127117 | 2005 | Case report | J Gerontol A | Angle-closure glaucoma after donepezil was discontinued |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 2479L | Aricept | Tablet containing donepezil hydrochloride 10 mg (oral) | Not listed in the data compiled for this report |
Safety Considerations
Contraindication-related conditions (from the TxGNN knowledge graph, not product label text): epilepsy, asthma (including intrinsic and allergic asthma), bladder neck obstruction, active peptic ulcer disease, sick sinus syndrome (including familial), and atrioventricular block.
Drug interactions (DDInter, 100 interactions recorded; a selection is shown):
- Major: bupropion
- Moderate: famotidine, ranitidine, cimetidine, hyoscyamine, atropine (including ophthalmic), glycopyrronium, clidinium, dicyclomine, loperamide, dexamethasone, metronidazole, dolasetron, picosulfuric acid, polyethylene glycol (3350 with electrolytes)
- Minor: aprepitant, acetylsalicylic acid, lorcaserin, clarithromycin
Indication-specific concerns:
- A 2025 systematic review and several case reports link cholinesterase inhibitors to movement disorders (for example Pisa syndrome and jaw tremor), which conflicts with the proposed use in movement disorders.
- Peptic ulcer risk matters for the tremor-nystagmus-duodenal ulcer syndrome prediction.
- Safety in porphyria has not been evaluated.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The top-ranked prediction (psychogenic movement disorders) has no trials or literature. The best-supported prediction, chronic tic disorder, rests on one small open-label study, case reports and mouse data, so it is a research question rather than a candidate for clinical adoption. Evidence for the movement-disorder predictions also contains conflicting benefit and harm signals.
To proceed, the following is needed:
- Controlled trials (ideally randomised, placebo-controlled) of donepezil in chronic tic disorder, with registration on ClinicalTrials.gov or ANZCTR
- Detailed mechanism of action data
- TGA Product Information warnings and contraindications for Aricept, and the approved indication text for ARTG 2479L
- A safety review for the target populations (especially children and adolescents, patients with cardiac conduction disorders, asthma, epilepsy or peptic ulcer disease) and for movement-disorder worsening
- Confirmation of Australian PBS listing and indication status, which was a flagged gap in the data compiled for this report
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.