Donepezil - Pharmacotherapy with the second generation acetylcholinesterase inhibitor in Alzheimer's dementia

During the last decade new antidementive drugs have been developed based on the hypothesis of a cholinergic deficiency contributing to the cognitive deficit in Alzheimer's dementia (AD). A positive effect on the progression of cognitive decline has been demonstrated for cholinesterase (ChE) inhibitors. New cholinergic drugs acting selectively on muscarinic or nicotinic receptors are currently developed or clinically studied. This review focuses on the second generation ChE inhibitor donepezil, a piperidine-based derivative with a high degree of selectivity, for acetylcholinesterase (AChE) in the CNS. Donepezil has been approved for the treatment of mild to moderate AD in Germany in October 1997. The effectiveness of donepezil has been demonstrated in several controlled clinical trials including more than 1100 AD patients. A dual outcome assessment strategy was rued in these studies. Cognitive performance assessed with the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) was found to improve during donepezil treatment compared to placebo and to baseline, respectively Furthermore, an improvement in four major arms of patient functioning (general, cognitive, behavioral and activities of daily living) was detected using a Clinician's Interview Based Impression of Change (CIBIC-plus). Donepezil treatment is started with 5 Mg once daily. Therapeutic effectiveness has been proven for this dosage. It is recommended to increase the dosage to a maximum of 10 mg once daily only after 4 to 6 weeks of treatment with 5 Mg. Although no statistically significant difference was found between 5 mg and 10 mg daily, the 10 mg dosage appeared to be superior to 5 mg regarding the impact on activities of daily living and the response rate. In general, donepezil was well tolerated and no hepatotoxicity was observed The dosage once daily due to the prolonged half-life of approximately 70 hours is advantageous in patients living alone without a permanent car e-giver. Under these circumstances the patient compliance can be controlled easily once daily by a relative or a nurse.