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Am Fam Physician. 2018;97(11):700

Original Article: Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms

Issue Date: June 15, 2017

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To the Editor: As subspecialists in geriatric psychiatry and pharmacy, we appreciate this concise and informative review of pharmacologic and nonpharmacologic therapies for Alzheimer disease. We would, however, like to make a suggestion regarding the information in Table 1 on administration of cholinesterase inhibitors. The authors recommend administering donepezil (Aricept) at bedtime and other oral cholinesterase inhibitors, specifically galantamine (Razadyne) and rivastigmine (Exelon), once or twice daily depending on whether the formulation is extended release.

The most common adverse effects of cholinesterase inhibitors include nausea, diarrhea, vomiting, decreased appetite, dyspepsia, anorexia, muscle cramps, fatigue, insomnia, dizziness, headache, and asthenia.13 Taking these medications with food, preferably a full meal, can mitigate these gastrointestinal effects. Therefore, we recommend taking cholinesterase inhibitors with food whenever possible to improve tolerability. Furthermore, administering these medications with a meal delays drug absorption, which reduces the peak plasma and brain concentrations, thereby decreasing the risk of all acute adverse effects.4 Fortunately, the package inserts for galantamine and rivastigmine recommend dosing with meals.2,3 However, the package insert for donepezil mentions only nightly dosing.1 When donepezil is administered nightly, plasma levels of the drug peak in three to four hours,5 likely contributing to the incidence of insomnia and abnormal dreams.

The only justification we are aware of for nightly dosing is that peak blood levels and their accompanying adverse effects would occur while patients are asleep and, therefore, would go unnoticed. However, nausea can rouse one from sleep, and another common adverse effect, bradycardia, could predispose patients to nocturnal falls when moving from the bed to the toilet.

We recommend administering donepezil in the morning with a meal, and oral forms of galantamine and rivastigmine once or twice daily, depending on the formulation, with meals.

Editor's Note: This letter was sent to the authors of “Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms,” who declined to reply.

Email letter submissions to Letters should be fewer than 400 words and limited to six references, one table or figure, and three authors. Letters submitted for publication in AFP must not be submitted to any other publication. Letters may be edited to meet style and space requirements.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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