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Switching cholinesterase inhibitors in older adults with dementia

  • Fadi Massoud (a1), Julie Eve Desmarais (a2) and Serge Gauthier (a3)


Background: Cholinesterase inhibitors (ChEIs) represent the mainstay of symptomatic treatment in Alzheimer's disease. Three medications belonging to this class are presently widely available. These agents differ in their individual mechanisms of action and pharmacokinetic properties. Switching ChEIs can be a reasonable option in cases of intolerance or lack of clinical benefit.

Methods: A systematic literature search of switching ChEIs was conducted, and all studies specifically evaluating this issue were identified. Published consensus guidelines were also searched for recommendations on ChEI switching.

Results: Eight clinical studies are summarized and discussed. All of these studies are open-label or retrospective and they cannot be readily compared because of heterogeneity in design, number of patients, agents used, and endpoints. Switching in most of these studies was done for both “lack of benefit” or “loss of response” after up to 29 months of treatment. Nevertheless, the majority of studies did not include individuals switched for lack of response after several years of treatment. Lack of satisfactory response or intolerance with the initial agent was not predictive of similar results with the second agent.

Conclusions: In light of these findings, we propose the following practical approach to switching ChEIs: (1) in the case of intolerance, switching to a second agent should be done only after the complete resolution of side-effects following discontinuation of the initial agent; (2) in the case of lack of efficacy, switching can be done overnight, with a quicker titration scheme thereafter; (3) switching ChEIs is not recommended in individuals who show loss of benefit several years after initiation of treatment.


Corresponding author

Correspondence should be addressed to: Dr Fadi Massoud, Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame, Service de Gériatrie, 1560 Sherbrooke Est, Montreal, Quebec, H2L 4M1, Canada. Phone: +1 (514) 890–8000; Fax: +1 (514) 412–7506. Email:


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Auriacombe, S., Pere, J. J., Loria-Kanza, Y. and Vellas, B. (2002). Efficacy and safety of rivastigmine in patients with Alzheimer's disease who failed to benefit from treatment with donepezil. Current Medical Research and Opinion, 18, 129138.
Bartorelli, L. et al. (2005). Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer's disease. Current Medical Research and Opinion, 21, 18091818.
Bullock, R. and Connolly, C. (2002). Switching cholinesterase inhibitor therapy in Alzheimer's disease: donepezil to rivastigmine, is it worth it? International Journal of Geriatric Psychiatry, 17, 288289.
Burns, A. et al. (2006). Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. Journal of Psychopharmacology, 20, 732755.
Dantoine, T., Auriacombe, S., Sarazin, M., Becker, H., Pere, J. J. and Bourdeix, I. (2006). Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment. International Journal of Clinical Practice, 60, 110118.
Darreh-Shori, T. et al. (2002). Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months. Neurology, 59, 563572.
Darvesh, S., Hopkins, D. A. and Geula, C. (2003). Neurobiology of butyrylcholinesterase. Nature Reviews Neurosciences, 4, 131138.
Davidsson, P., Blennow, K., Andreasen, N., Eriksson, B., Minthon, L. and Hesse, C. (2001). Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease. Neuroscence Letters, 300, 157160.
Dybicz, S. B., Keohane, D. J., Erwin, W. G., McRae, T. and Shah, S. N. (2006). Patterns of cholinesterase-inhibitor use in the nursing home setting: a retrospective analysis. American Journal of Geriatric Pharamacotherapy, 4, 154160.
Gardette, V. et al. (2010). Predictive factors of discontinuation and switch of cholinesterase inhibitors in community-dwelling patients with Alzheimer's disease: a 2-year prospective, multicentre, cohort study. CNS Drugs, 24, 431442.
Gauthier, S., Juby, A., Morelli, L., Rehel, B. and Schecter, R. (2006). A large, naturalistic, community-based study of rivastigmine in mild-to-moderate AD: the EXTEND Study. Current Medical Research and Opinion, 22, 22512265.
Herrmann, N. et al. (2007). A population-based study of cholinesterase inhibitor use for dementia. Journal of the American Geriatrics Society, 55, 15171523.
Herrmann, N., Binder, C., Dalziel, W., Smyth, S. and Camacho, F. (2009). Persistence with cholinesterase inhibitor therapy for dementia: an observational administrative health database study. Drugs and Aging, 26, 403407.
Hogan, D. B. et al. (2007). Management of mild to moderate Alzheimer's disease and dementia. Alzheimers and Dementia, 3, 355384.
Jann, M. W., Shirley, K. L. and Small, G. W. (2002). Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clinical Pharmacokinetics, 41, 719739.
Massoud, F. and Gauthier, S. (2010). Update on the pharmacological treatment of Alzheimer's disease. Current Neuropharmacology, 8, 6980.
Mohs, R. C. et al. (2001). A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology, 57, 481488.
Mucha, L., Shaohung, S., Cuffel, B., McRae, T., Mark, T. L. and Del, V. M. (2008). Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer's disease. Journal of Managed Care Pharmacy, 14, 451461.
Onor, M. L., Trevisiol, M. and Aguglia, E. (2007). Rivastigmine in the treatment of Alzheimer's disease: an update. Clinical Interventions in Aging, 2, 1732.
Perry, E. K., Perry, R. H., Blessed, G. and Tomlinson, B. E. (1978). Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathology and Applied Neurobiology, 4, 273277.
Robinson, D. M. and Plosker, G. L. (2006). Galantamine extended release in Alzheimer's disease: profile report. Drugs and Aging, 23, 839842.
Rogers, S. L., Doody, R. S., Pratt, R. D. and Ieni, J. R. (2000). Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: final analysis of a U.S. multicentre open-label study. European Neuropsychopharmacology, 10, 195203.
Sadowsky, C. H. et al. (2005). Switching from donepezil to rivastigmine is well tolerated: results of an open-label safety and tolerability study. Primary Care Companion to Journal of Clinical Psychiatry, 7, 4348.
Sadowsky, C. H., Dengiz, A., Olin, J. T., Koumaras, B., Meng, X. and Brannan, S. (2009). Switching from donepezil tablets to rivastigmine transdermal patch in Alzheimer's disease. American Journal of Alzheimer's Disease and Other Dementias, 24, 267275.
Seltzer, B. (2007). Donepezil: an update. Expert Opinion Pharmacotherapy, 8, 10111023.
Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S. and Gergel, I. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA, 291, 317324.
Wilkinson, D. G. and Howe, I. (2005). Switching from donepezil to galantamine: a double-blind study of two wash-out periods. International Journal of Geriatric Psychiatry, 20, 489491.


Switching cholinesterase inhibitors in older adults with dementia

  • Fadi Massoud (a1), Julie Eve Desmarais (a2) and Serge Gauthier (a3)


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