Table 1.

Currently approved therapies for AD

	Donepezil HCl [14]	Rivastigmine [16, 24]	Galantamine HBr [15]	Memantine [43]	Memantine and Donepezil [67]
Class	ChEI	ChEI/BuChEI	ChEI	NMDA receptor antagonist	ChEI and NMDA receptor antagonist combination
US approval	1996	2000	2001	2003	2014
Available forms	Tablets: 5, 10, and 23 mg ODT: 5 and 10 mg	Capsules: 1.5, 3, 4.5, and 6 mg Oral solution: 2 mg/mL TD patch: 4.6, 9.5, and 13.3 mg/24 h	ER capsules: 8, 16, and 24 mg Tablets: 4, 8, and 12 mg Oral solution: 4 mg/mL	ER capsules: 7, 14, 21, and 28 mg Tablets: 5 and 10 mg Oral solution: 2 mg/mL	ER capsules: 7, 14, 21, and 28 mg memantine with 10 mg donepezil
Indications	Treatment of mild, moderate, and severe Alzheimer-type dementia	Treatment of mild to moderate (all formulations) and severe (patch only) Alzheimer-type dementia and mild to moderate dementia associated with PD	Treatment of mild to moderate Alzheimer-type dementia	Treatment of moderate to severe Alzheimer-type dementia	Treatment of moderate to severe Alzheimer-type dementia in patients stabilized on 10 mg donepezil hydrochloride QD
Dosage	5–10 mg QD (mild to moderate) 10–23 mg QD (moderate to severe)	Capsule/oral solution: initial treatment 1.5 mg BID, thereafter 3–6 mg as tolerated BID Patch: initial treatment 4.6 mg/24 h, thereafter 9.5–13.3 mg/24 h	ER capsules: starting dose 8 mg QD, thereafter 16–24 mg QD Tablets and oral solution: starting dose 4 mg BID, thereafter 8–12 mg BID	ER capsules: starting dose 7 mg QD, thereafter increase 7 mg increments up to maintenance dose of 28 mg QD; in patients with severe renal impairment, recommended dose is 14 mg QD Tablets/oral solution: Starting dose 5 mg QD, thereafter increase 5 mg increments to maintenance dose of 10 mg BID; in patients with severe renal impairment, recommended dose is 5 mg BID	Starting dose 7 mg/10 mg QD, thereafter increase memantine 7 mg increments up to maintenance dose of 28 mg/10 mg QD; in patients with severe renal impairment, recommended dose is 14 mg/10 mg QD
Drug interactions	May interfere with the activity of anticholinergic medications; possible synergistic effect with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists	Concomitant use with metoclopramide, β-blockers, or cholinomimetic and anticholinergic drugs is not recommended	May interfere with the activity of anticholinergic medications; a possible synergistic effect with concomitant administration of succinylcholine, other ChEIs, similar neuromuscular blocking agents, or cholinergic agonists	Concomitant use with drugs that make urine alkaline (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) and other NMDA antagonists (e.g., amantadine, ketamine, dextromethorphan) is not recommended	May interfere with the activity of anticholinergic medications; a possible synergistic effect with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists; use caution with other NMDA antagonists
Common AEs	Nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia	Nausea, vomiting, anorexia, dyspepsia, diarrhea, and asthenia	Nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite	Headache, diarrhea, and dizziness	Headache, diarrhea, and dizziness (memantine); diarrhea, anorexia, vomiting, nausea, and ecchymosis (donepezil)

AD, Alzheimer’s disease; AE, adverse event; BID, twice daily; BuChEI, butyrylcholinesterase inhibitor; ChEI, cholinesterase inhibitor; ER, extended release; HBr, Hydrobromide; HCl, Hydrochloride; NMDA, N-methyl-D-aspartate; ODT, orally disintegrating tablet; PD, Parkinson's disease; QD, once daily; TD, Transdermal.