Summary
Donepezil has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Parkinson's Disease would be drug repurposing rather than first-in-human development. This does not mean it is approved for Parkinson's Disease. ClinicalTrials.gov lists 8 registered trials linking Donepezil to Parkinson's Disease: 5 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00030979). The largest enrolment is 357 participants (NCT01327859). Registration activity spans 2002 to 2024. The literature layer holds 7 publications for this pair: 1 Cochrane review, 2 meta-analyses and 4 clinical trial publications. Publication years run from 2005 to 2024. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Parkinson Disease ranks 540 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Progressive neurodegeneration — no spontaneous remission; untreated motor decline averages 3-5 UPDRS points/year; non-motor symptoms (depression, cognitive decline, autonomic dysfunction) also progressive.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 66.5 (trials 25.5, literature 21.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 5 completed, 3 other |
| Linked publications | 7 (4 clinical trial publications, 2 meta-analyses, 1 Cochrane review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| Data sources | DGIdb |
| Linked via biomarker / target | ACHE |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT00030979 | Donepezil to Treat Dementia in Parkinson's Disease 2002 | completed | Phase 4 | 28 |
| NCT03011476 | Effect of Acetylcholinesterase Inhibitors on the Gait of the Patients With Parkinson Disease 2017 | status unknown | Phase 4 | 20 |
| NCT01327859 | Safety, Tolerability, and Efficacy of Donepezil (Aricept) in Parkinson' s Disease (PD) Patients With Dementia 2003 | completed | Phase 3 | 357 |
| NCT01014858 | Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease 2013 | terminated | Phase 3 | 64 |
| NCT02206620 | Effects of Cholinergic Augmentation on Measures of Balance and Gait 2014 | completed | Phase 2 | 49 |
| NCT06903910 | Investigating the Cholinergic Contribution to Gait Dysfunction in Parkinson's Disease 2024 | completed | Phase 2 | 6 |
| NCT02857244 | A Multidisciplinary Approach to Manage Gait Difficulty in Parkinson Patients 2016 | withdrawn | Phase 2 | — |
| NCT02012595 | [11C]Donepezil PET For Imaging The Autonomous Nervous System In Parkinsons Disease 2013 | completed | Not applicable | 24 |
Published literature
- Clinical trial publication [Dementia with Lewy bodies and Parkinson disease dementia, their diagnoses and treatment strategies]Takeda A · Nihon yakurigaku zasshi. Folia pharmacologica Japonica · 2024 · PMID 38171841
- Meta-analysis Cholinesterase Inhibitors for Delusions and Hallucinations in Alzheimer Disease and Parkinson Disease: Questionably Significant BenefitsAndrade C · The Journal of clinical psychiatry · 2023 · PMID 37530610
- Meta-analysis Cholinesterase Inhibitors for Treatment of Psychotic Symptoms in Alzheimer Disease and Parkinson Disease: A Meta-analysisd'Angremont E, Begemann MJH, van Laar T et al. · JAMA neurology · 2023 · PMID 37358841
- Clinical trial publication Early-start vs delayed-start donepezil against cognitive decline in Parkinson disease: a randomized clinical trialSawada H, Oeda T, Kohsaka M et al. · Expert opinion on pharmacotherapy · 2021 · PMID 32867552
- Clinical trial publication Effects of a central cholinesterase inhibitor on reducing falls in Parkinson diseaseChung KA, Lobb BM, Nutt JG et al. · Neurology · 2010 · PMID 20810998
- Cochrane review Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of NeurologyMiyasaki JM, Shannon K, Voon V et al. · Neurology · 2006 · PMID 16606910
- Clinical trial publication Efficacy and safety of donepezil in the treatment of executive dysfunction in Parkinson disease: a pilot studyLinazasoro G, Lasa A, Van Blercom N · Clinical neuropharmacology · 2005 · PMID 16062096
Mechanism and notes
Recorded mechanism or class: inhibitor.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ACHE. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Donepezil approved for Parkinson's Disease?
Donepezil has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Parkinson's Disease would be drug repurposing rather than first-in-human development. This does not mean it is approved for Parkinson's Disease. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Donepezil in clinical trials for Parkinson's Disease?
ClinicalTrials.gov lists 8 registered trials linking Donepezil to Parkinson's Disease: 5 have completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT00030979). The largest enrolment is 357 participants (NCT01327859). Registration activity spans 2002 to 2024.
What does the evidence show for Donepezil in Parkinson's Disease?
Donepezil has both completed registered trials and synthesis-level publications linked to Parkinson's Disease. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ACHE. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.