Donepezil by Ray Sahelian, M.D. Aricept

Donepezil is a reversible inhibitor of the enzyme acetylcholinesterase. Donepezil is thought to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil’s effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that donepezil alters the course of the underlying dementing process.

Donepezil Side Effects

The most common donepezil side effects include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia.

Long term donepezil treatment outcome
Donepezil in Alzheimer's disease: what to expect after 3 years of treatment in a routine clinical setting.
Dement Geriatr Cogn Disord. 2007;23(3):150-60. Clinical Memory Research Unit, Department of Clinical Sciences, Malmo, Lund University, Malmo, Sweden.
Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. The Swedish Alzheimer Treatment Study is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting.

Donepezil and dementia
Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia.
Am J Geriatr Psychiatry. 2007 Jan;15(1):84-7. Mendez MF, Shapira JS, McMurtray A, Licht E. Department of Neurology, University of California at Los Angeles, Los Angeles, CA.
The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia. Twelve patients with frontotemporal dementia who received donepezil for six months were compared with 12 frontotemporal dementia controls on behavioral measures. The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the frontotemporal dementia 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 frontotemporal dementia can experience worsening of symptoms with donepezil.