Table 1. Summary of Studies Regarding the Various Therapeutic Potentials of Donepezil.
| Type of Disease | Author | Type of Study | Dosage and Method of Administration | Number of Participants | Outcomes Summary |
|---|---|---|---|---|---|
| Donepezil and Non-Alzheimer's Dementia | |||||
| Parkinson's dementia | Wang et al. (32) | Systematic review and meta-analysis | 5 and 10 mg/daily, oral | Five trials examining DPZ | DPZ improved patients' daily functioning and cognitive symptoms. It was safe and could be helpful for MCI-PD, PDD, and LBD. |
| Vascular dementia | Kim et al. (33) | Meta-analysis | 5 and 10 mg/daily, oral | Five trials examined DPZ | AChEIs, including DPZ, significantly improved memory scale scores and maintained this improvement within 24 weeks through a stable pattern. They were well-tolerated. |
| Vascular dementia | Battle et al. (34) | Meta-analysis and network meta-analysis | 5 and 10 mg/daily, oral | Three trials studying DPZ (2,193 participants) | According to the meta-analysis, DPZ 5 and 10 mg had a negligible effect on cognitive improvement, although the side effects of the 10 mg dose were higher; However, according to the network meta-analysis, all AChEIs were more effective and safer than placebo. |
| Traumatic-brain injury dementia | Wheaton et al. (35) | Meta-analysis | 5 - 10 mg/day, oral | Six studies (DPZ/DPZ + physostigmine + lecithin) | Improvement of memory and attention impairment in the post-acute phase of TBI |
| Traumatic brain injury dementia | Campbell et al. (36) | Retrospective, longitudinal analysis | 5 - 10 mg/day, oral | 129 patients (55 patients in the DPZ group) | There was no significant difference between the two groups regarding cognitive factors such as processing speed, attention, and memory. |
| Donepezil and Non-dementia Diseases | |||||
| Parkinson's disease | Chung et al. (37) | Cross-over RCT | 5 - 10 mg/day, oral | 23 patients with PD with falls or near falls > 2 times per week | The number of falls per day in the DPZ group was almost half that of the placebo group. |
| Parkinson's disease | Chen et al. (12) | Meta-analysis | 5 and 10 mg/daily, oral | Three studies examining DPZ | AChEIs could not significantly improve gait and imbalance, although these drugs appeared to be relatively effective in regulating steps during a single activity. |
| Mood disorders | Reynolds et al. (38) | Clinical trial | 5 - 10 mg/day, oral | 130 patients with normal cognition or MCI | Improvement of executive function and memory; More recurrence of depression than the placebo group |
| Mood disorders | Fitzgerald et al. (39) | Animal study | 0.02 - 0.2 mg/kg, and 2 mg/kg, intraperitoneally injected | 160 mice | The antidepressant-like effect at lower doses and depressant-like effect at higher doses |
| Mood disorders | Hosseini et al. (40) | Clinical trial | 5 mg/day, oral | 73 patients aged 20 - 50 years old (37 patients in the DPZ group and the rest in the placebo group) | DPZ significantly improved cognitive impairment caused by SSRIs |
| Autism spectrum disorders | Gabis et al. (41) | Clinical trial | 2.5 - 5 mg/day, and DPZ 5 mg/day + Choline 350 mg/day for four weeks, oral | 60 autistic children and adolescents (5 - 16 years old) | Significant safety and efficacy in young children (younger than 10 years old); Less effective in adolescents with some significant side effects like increased irritability. |
| Autism spectrum disorders | Rossignol and Frye (42) | Systematic review | 2.5 - 30 mg/day, oral | Seven studies | Five studies showed improvement of many ASD symptoms (four of five case series and one of two RCTs). |
| Immune system and infectious disease | Abe et al. (43) | Retrospective cohort study | - | 25,602 hospitalized elderlies with pneumonia (578 patients taking DPZ for dementia) | DPZ acted as an independent factor in reducing hospitalized pneumonia patients' mortality. |
| Immune system and infectious disease | Sochocka et al. (44) | Experimental | 5 - 100 µg/mL, in vitro | PBLs from 30 blood samples (15 with resistant leukocytes to VSV and 15 with sensitive leukocytes) treated with DPZ or EGB-761 | 10 - 50 μg/mL DPZ increased resistance of human leukocytes and reduced activation of NF-κB. |
Abbreviations: AChEI, acetylcholinesterase inhibitor; DPZ, donepezil hydrochloride; EGB 761, Ginkgo biloba extract EGb 761; LBD, lewy body dementia; MCI, mild cognitive impairment; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PBLs, peripheral blood leukocytes; PD, Parkinson’s disease; PDD, Parkinson’s disease dementia; RCT, randomized controlled trial; SSRIs, selective serotonin reuptake inhibitors; TBI, traumatic brain injury; VSV, vesicular stomatitis virus.