The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury

Campbell, Kelsey; Kennedy, Richard E.; Brunner, Robert; Hollis, Sean; Lumsden, Ross; Novack, Thomas A.

doi:10.1080/02699052.2018.1468574

Cited by 11 publications

(4 citation statements)

References 47 publications

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“…These favorable effects on TBI have been reported both in human subjects and in rodent models 62 – 65 . While not all of the studies have found therapeutic effects, either in rodents or humans 66 , 67 , a body of literature supports their efficacy under some conditions 68 , including demonstration in a double-blind placebo-controlled study of donepezil 69 .…”

Section: Discussionmentioning

confidence: 99%

The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test

et al. 2020

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Finding new antidepressant agents is of high clinical priority given that many cases of major depressive disorder (MDD) do not respond to conventional monoaminergic antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Recent findings of effective fast-acting antidepressants indicate that there are biological substrates to be taken advantage of for fast relief of depression and that we may find further treatments in this category. In this vein, the cholinergic system may be a relatively overlooked target for antidepressant medications, given its major role in motivation and attention. Furthermore, the classically engaged monoaminergic neurotransmitter systems in depression treatment—serotonin, norepinephrine, and dopamine—interact directly at times with cholinergic signaling. Here we investigate in greater detail how the cholinergic system may impact depression-related behavior, by administering widely ranging doses of the cholinesterase inhibitor drug, donepezil, to C57BL/6J mice in the forced swim test. First, we confirm prior findings that this drug, which is thought to boost synaptic acetylcholine, promotes depression-like behavior at a high dose (2.0 mg/kg, i.p.). But we also find paradoxically that it has an antidepressant-like effect at lower doses (0.02 and 0.2 mg/kg). Further this antidepressant-like effect is not due to generalized hyperactivity, since we did not observe increased locomotor activity in the open field test. These data support a novel antidepressant-like role for donepezil at lower doses as part of an overall u-shaped dose-response curve. This raises the possibility that donepezil could have antidepressant properties in humans suffering from MDD.

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Section: Discussionmentioning

confidence: 99%

The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test

et al. 2020

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“…Campbell et al made a retrospective comparison of the effect of donepezil (starting 5 mg daily and increasing to 10 mg daily seven to 10 days after starting treatment) with rehabilitation therapy on cognitive factors during the acute recovery phase of moderate to severe TBI among 129 patients (55 in the donepezil group and 74 in the rehabilitation group). They found that the two groups had no significant differences (Table 1) (36). However, many studies recommend a dose of 5 -10 mg to treat TBI-induced cognitive impairment (58-60).…”

Section: Traumatic Brain Injury Dementiamentioning

confidence: 97%

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

et al. 2022

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: Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.

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“…Results showed no significant improvement across a range of standardized memory measures including the subgroup of participants with MS-TBI. 108 The use of donepezil in acute and subacute TBI populations was not supported in a study by Campbell et al, 109 who employed a retrospective longitudinal analysis of nonrandomly prescribed donepezil with 55 participants with MS-TBI compared with 74 controls receiving standard TBI treatment. No significant differences were found on standardized memory measures or on the Disability Rating Scale or Functional Independence Measure scores.…”

Section: Memory #5: Group-based Interventions May Be Considered For T...mentioning

confidence: 99%

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory

Velikonja¹,

Ponsford

Janzen³

et al. 2023

Journal of Head Trauma Rehabilitation

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Introduction: Memory impairments affecting encoding, acquisition, and retrieval of information after moderate-to-severe traumatic brain injury (TBI) have debilitating and enduring functional consequences. The interventional research reviewed primarily focused on mild to severe memory impairments in episodic and prospective memory. As memory is a common focus of cognitive rehabilitation, clinicians should understand and use the latest evidence. Therefore, the INCOG (“International Cognitive”) 2014 clinical practice guidelines were updated. Methods: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for intervention for memory impairments post-TBI, a decision-making algorithm, and an audit tool for review of clinical practice. Results: The interventional research approaches for episodic and prospective memory from 2014 are synthesized into 8 recommendations (6 updated and 2 new). Six recommendations are based on level A evidence and 2 on level B. In summary, they include the efficacy of choosing individual or multiple internal compensatory strategies, which can be delivered in a structured or individualized program. Of the external compensatory strategies, which should be the primary strategy for severe memory impairment, electronic reminder systems such as smartphone technology are preferred, with technological advances increasing their viability over traditional systems. Furthermore, microprompting personal digital assistant technology is recommended to cue completion of complex tasks. Memory strategies should be taught using instruction that considers the individual's functional and contextual needs while constraining errors. Memory rehabilitation programs can be delivered in an individualized or mixed format using group instruction. Computer cognitive training should be conducted with therapist guidance. Limited evidence exists to suggest that acetylcholinesterase inhibitors improve memory, so trials should include measures to assess impact. The use of transcranial direct current stimulation (tDCS) is not recommended for memory rehabilitation. Conclusion: These recommendations for memory rehabilitation post-TBI reflect the current evidence and highlight the limitations of group instruction with heterogeneous populations of TBI. Further research is needed on the role of medications and tDCS to enhance memory.

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The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury

Abstract: Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

Cited by 11 publications

References 47 publications

The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test

The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory

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