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• W2012199657 abstract "Back to table of contents Previous article Next article LetterFull AccessAn Open-Label Trial of Donepezil (Aricept) in the Treatment of Persons With Mild Traumatic Brain InjuryNeil S. Kaye, M.D., , John B. Townsend III, M.D., and Richard Ivins, Ph.D.Neil S. KayeSearch for more papers by this author, M.D., Clinical Assistant Professor of Psychiatry and Human Behavior and Clinical Assistant Professor of Family Medicine, Jefferson Medical College, Philadelphia, Pennsylvania., John B. Townsend IIISearch for more papers by this author, M.D., and Richard IvinsSearch for more papers by this author, Ph.D.Published Online:1 Aug 2003AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: We read with interest, the review by Griffin et. al.1 on the use of cholinergic agents in the treatment of persons who sustained traumatic brain injury (TBI). As early as 1997 (Poster session at the joint meeting of the American Neuropsychiatric Association and the British Neuropsychiatry Association. Cambridge, England.), we too suspected that these medications might be beneficial in treating cognitive dysfunction, memory deficits, and emotional instability, all observed in TBI.Our findings revealed the following Table 1:An Open-Label Trial of Donepezil (Aricept) in the Treatment of Persons with Mild Traumatic Brain InjuryMethods:In an open label trial, subjects who participated in this pilot program were the first 10 consecutive patients known to have sustained TBI and received treatment in one outpatient practice after the release of donepezil. Patients were given 5 mg daily for the first 4 weeks and 10 mg daily for the second 4 weeks. Pretreatment and posttreatment neuropsychiatric evaluations, including clinical global improvement (CGI) ratings and a symptom focused neuropsychological test battery, were used to measure responses to the medication.Results:Eighty percent (8/10) of the subjects completed the study. One subject withdrew due to noncompliance, and another dropped out out due to intolerable GI side effects of nausea. This heterogeneous group ranged in age from 26–60 years, with a mean of 41 years. Severity of head injury included mild (6 cases), moderate (1 case), and severe (3 cases). Time since head injury ranged from 1 to 5 years, with a mean of 1.2 years.Discussion:Although we predicted improvement in the domain of memory, we were unable to document any such positive change. The Global Memory Scale (GMS) of the Memory Assessment Scale (MAS) does not seem to improve (MAS margin of error is +/−4 points.) However, CGI's conducted by two independent raters showed improvement. Patients also rated themselves somewhat improved in most cases, but not necessarily in the memory domain as expected. The overall impression was that they had improved focus, attention and clarity of thought while on the medication. A number of patients commented that their speed of processing appeared to be better or they were able to keep multiple ideas in mind simultaneously. Family members frequently described improved socialization.We are encouraged by the results and believe that further study of donepezil in TBI is indicated. We would recommend assessing change by using other test instruments, such as the Categories Test, which is better suited to assess cognitive flexibility, nonverbal abstract reasoning, learning from mistakes, and incidental visual memory. In addition, a larger trial should, as a minimum, control for age, severity of injury, time since injury, and intelligence quotient (IQ). A subsequent controlled trial that uses traditional blinding methods and placebo could follow if warranted. Of note, is that at the end of the study, seven of the eight subjects who completed the study (88%) elected to remain on donepezil, as they believed it was efficacious. The only subject who completed the study and did not elect to stay on the medication reported a positive effect on memory, but experienced nausea as a side effect.Conclusion:Testing Donepezil—which is approved, available, and well tolerated—in a patient population that historically has limited progress should prove useful. As in Alzheimer's disease (AD), the acetylcholinesterase inhibitors may be of greater benefit in the overall functioning of the individual than the specific domain of memory.2Dr. Base-XML-tag-lib speaks for Pfizer Phamaceuticals. He has never owned stock in the corporation and has never been an employee. No funding from any outside source was used in this study.An Open-Label Trial of Donepezil (Aricept) in Brain InjuryEnlarge tableReferences1 Griffin S, et al: A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci 2003; 15:1, 17–26Crossref, Medline, Google Scholar2 Rogers S, et al: Donepezil improves cognition and global function in Alzheimer disease. Arch Intern Med 1998; 14:197–230Google Scholar FiguresReferencesCited byDetailsCited ByPharmacotherapy for mild traumatic brain injury: an overview of the current treatment options20 March 2022 | Expert Opinion on Pharmacotherapy, Vol. 23, No. 7Mitoquinone supplementation alleviates oxidative stress and pathologic outcomes following repetitive mild traumatic brain injury at a chronic time pointExperimental Neurology, Vol. 351Acetylcholinesterase inhibitors to enhance recovery from traumatic brain injury: a comprehensive review and case series3 February 2022 | Brain Injury, Vol. 36, No. 4Association of Pharmacological Interventions With Symptom Burden Reduction in Patients With Mild Traumatic Brain InjuryJAMA Neurology, Vol. 78, No. 5Volume Change in Frontal Cholinergic Structures After Traumatic Brain Injury and Cognitive Outcome13 August 2020 | Frontiers in Neurology, Vol. 11Pharmacologic Treatment of Neurobehavioral Sequelae Following Traumatic Brain InjuryCritical Care Nursing Quarterly, Vol. 43, No. 2Brain Injury, Vol. 32, No. 8Journal of Neurotrauma, Vol. 35, No. 11Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury: A PET StudyJournal of Head Trauma Rehabilitation, Vol. 33, No. 1Mild Traumatic Brain Injury and Post-concussion SyndromeSports Medicine and Arthroscopy Review, Vol. 24, No. 3Journal of Neurotrauma, Vol. 32, No. 19Brain Injury, Vol. 29, No. 10INCOG Recommendations for Management of Cognition Following Traumatic Brain Injury, Part VJournal of Head Trauma Rehabilitation, Vol. 29, No. 4Journal of Neurotrauma, Vol. 31, No. 2Impact of Pharmacological Treatments on Cognitive and Behavioral Outcome in the Postacute Stages of Adult Traumatic Brain InjuryJournal of Clinical Psychopharmacology, Vol. 31, No. 6Psychopharmacological Treatment for Cognitive Impairment in Survivors of Traumatic Brain Injury: A Critical ReviewBrian W. Writer, D.O.Jason E. Schillerstrom, M.D.1 October 2009 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 21, No. 4Brain Injury, Vol. 23, No. 6The Effectiveness of Donepezil for Cognitive Rehabilitation After Traumatic Brain InjuryJournal of Head Trauma Rehabilitation, Vol. 23, No. 3Use of Donepezil in the Treatment of Cognitive Impairments of Moderate Traumatic Brain InjuryMonique Foster, M.D.David R. SpiegelM.D.,1 January 2008 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 20, No. 1Brain Injury, Vol. 22, No. 7-8Brain Injury, Vol. 20, No. 3Expert Opinion on Drug Metabolism & Toxicology, Vol. 1, No. 3 Volume 15Issue 3 August 2003Pages 383-384 Metrics PDF download History Published online 1 August 2003 Published in print 1 August 2003" @default.
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