Preliminary Findings: Behavioral Worsening on Donepezil in Patients With Frontotemporal Dementia
Abstract
Objective The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD). Methods Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures. Results The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication. Conclusion There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.
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Some bvFTD patients may experience behavioral or cognitive deterioration when exposed to acetylcholinesterase inhibitors.
“In fact, some bvFTD patients may experience behavioral or cognitive deterioration when exposed to these agents [37].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [37]
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“Cholinesterase inhibitors, such as donepezil, do not alleviate but can even exacerbate behavioral disturbance in patients with FTD (89).”
BackgroundPharmacotherapy for Neuropsychiatric Symptoms in Frontotemporal Dementia
Le, C., & Finger, E. (2021) · CNS Drugs · doi:10.1007/s40263-021-00854-5 · Cited by 26 · see citing works
New Approaches to the Treatment of Frontotemporal Dementia
Neylan, K. D., & Miller, B. L. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01380-6 · Cited by 26 · see citing works
“Cholinesterase inhibitors, one of the primary classes of medications used in the treatment of AD which include donepezil, rivastigmine, and galantamine, have been studied in FTD and show no effect on cognitive performance but can actually worsen neuropsychiatric symptoms [15, 36].”
Soucy, J.-P., Bartha, R., Bocti, C., Borrie, M., Burhan, A. M., Laforce, R., & Rosa-Neto, P. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt199 · Cited by 25 · see citing works
Cholinergic depletion and basal forebrain volume in primary progressive aphasia
Schaeverbeke, J., Evenepoel, C., Bruffaerts, R., van Laere, K., Bormans, G., Dries, E., Tousseyn, T., Nelissen, N., Peeters, R., Vandenbulcke, M., et al. (2016) · NeuroImage: Clinical · doi:10.1016/j.nicl.2016.11.027 · Cited by 25 · see citing works
“A therapeutic trial of donepezil in FTD failed to show any efficacy and a subgroup of patients experienced worsening of symptoms (Mendez et al., 2007).”
BackgroundTherapeutic and diagnostic challenges for frontotemporal dementia
Dâ€TMAlton, S., & Lewis, J. M. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00204 · Cited by 25 · see citing works
“Antipsychotics and drugs targeting the cholinergic system appear to be largely Frontiers in Aging Neuroscience www.frontiersin.org August 2014 | Volume 6 | Article 204 | 1 ineffective (Mendez et al., 2007).”
BackgroundNew insights and therapeutic opportunities for progranulin-deficient frontotemporal dementia
Amin, S., Carling, G., & Gan, L. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.10.001 · Cited by 37 · see citing works
A Clinical Guide to Frontotemporal Dementias
Ljubenkov, P. A., & Miller, B. L. (2016) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20160018 · Cited by 32 · see citing works
Pharmacological treatment of frontotemporal lobar degeneration: systematic review.
Portugal, M. D. G., Marinho, V., & Laks, J. (2011) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462011000100016 · Cited by 23 · see citing works
“Two B studies did not evaluate cognitive functions.(12,33) The quality C studies showed a significant improvement in behavior with Selegiline.”
BackgroundPanza, F., Dibello, V., Sardone, R., Castellana, F., Zupo, R., Lampignano, L., Bortone, I., Stallone, R., Cirillo, N., Damiani, C., et al. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2233892 · Cited by 22 · see citing works
Logroscino, G., Imbimbo, B. P., Lozupone, M., Sardone, R., Capozzo, R., Battista, P., Zecca, C., Dibello, V., Giannelli, G., Bellomo, A., et al. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1598377 · Cited by 28 · see citing works
“and may also worsen behavioral symptoms [65].”
Overcoming apathy in frontotemporal dementia: challenges and future directions
Johnson, E., & Kumfor, F. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.01.022 · Cited by 22 · see citing works
Hall, G., Shapira, J., Gallagher, M., & Denny, S. S. (2013) · Journal of Gerontological Nursing · doi:10.3928/00989134-20130131-02 · Cited by 21
Self-citationWhat dementia reveals about proverb interpretation and its neuroanatomical correlates.
Kaiser, N., Lee, G., Lu, P., Mather, M. J., Shapira, J., Jimenez, E. E., Thompson, P., & Mendez, M. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2013.05.021 · Cited by 20 · see citing works
“Both AD and bvFTD have more rapid courses being early-onset forms of dementia (Huff et al., 1987), and are often misdiagnosed as psychiatric disorders, especially in the case of bvFTD (e.g. Mendez et al., 2007).”
Self-citationThe behavioral variant of frontotemporal dementia: An analysis of the literature and a case report
Birkhoff, J. M., Garberi, C., & Re, L. (2016) · International Journal of Law and Psychiatry · doi:10.1016/j.ijlp.2016.04.001 · Cited by 18 · see citing works
“…2004; Lebert et al., 2004; Manoocherhri & Huey, 2012; Mendez, Anderson, et al., 2005; Mendez, Chen, et al., 2005; Mendez, Shapira, et al., 2005; Mendez et al., 2007; Merrilees, 2007; Merrilees & Ketelle, 2010; Mocellin et al., 2015; Moretti et al., 2003, 2004; O'Brien et al., 2011; Pijnenburg…”
Fisher, T., Schwartz, A., Greenspan, H. N., & Heinrich, T. W. (2016) · International Journal of Psychiatry in Medicine · doi:10.1177/0091217416636579 · Cited by 19 · see citing works
“Acetylcholinesterase inhibitors have also been tried, but since research suggests that the behaviors can even worsen with these medications, this approach should generally be avoided.(26) Nonpharmacologic approaches are frequently used, targeting the environment and caregiver in an attempt to reduce triggering stimuli…”
BackgroundDemencia frontotemporal variante conductual: aproximación clínica y terapéutica
Fernández‐Matarrubia, M., Matías‐Guiu, J. A., Moreno‐Ramos, T., & Matías‐Guiu, J. (2013) · Neurología · doi:10.1016/j.nrl.2013.03.001 · Cited by 23 · see citing works
Treatment of the behavioral variant of frontotemporal dementia: a narrative review
Gambogi, L., Guimarães, H., de Souza, L. D., & Caramelli, P. (2021) · Dementia & Neuropsychologia · doi:10.1590/1980-57642021dn15-030004 · Cited by 19 · see citing works
- Authors
- Mendez, M. F., Shapira, J. S., McMurtray, A., & Licht, E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mendez, Mario F.
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 15
- Issue
- 1
- Pages
- 84-87
- ISSN
- 1064-7481 (ISSN-L)
- OpenAlex
- W2058247742
- Cited by
- 267
- References
- 0
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 9 · 2023: 13 · 2022: 11 · 2021: 23 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 16 · 2016: 19 · 2015: 6 · 2014: 19 · 2013: 18 · 2012: 11
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG19724-01, P01AG019724)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- donepezil, frontotemporal dementia, acetylcholinesterase inhibitors, behavioral disinhibition, compulsive behavior, adverse drug reactions, cognitive performance
- MeSH terms
- Donepezil, Behavioral Symptoms, Cholinesterase Inhibitors, Compulsive Behavior, Dementia, Female, Humans, Indans, Male, Middle Aged, Piperidines
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