title: Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?
abstract: OBJECTIVE
  The purpose of this systematic review was to review the current place in therapy of the 4 medications, donepezil, rivastigmine, galantamine, and memantine, approved for the treatment of Alzheimer disease (AD) since the publication of Phase III trials.
  
  
  METHODS
  A systematic literature search of MEDLINE and EMBASE was conducted for articles published in the past 10 years. The search was performed using the following Medical Subject Headings and text key words: Alzheimer's disease, treatment, donepezil, galantamine, rivastigmine, memantine, dementia of the Alzheimer's type, and dementia.
  
  
  RESULTS
  Studies that evaluated new doses, indications, and dose formulations remain a large part of the current literature. Donepezil gained approval for the treatment of severe AD and became available in a 23-mg/d dose formulation. Rivastigmine became available in a patch formulation. Memantine became available as an extended-release capsule. Use of a combination product formulation was recently approved, memantine extended release/donepezil. Controversy among clinicians remains regarding when to initiate therapy, appropriate duration of therapy, and how and when to discontinue the treatment of AD.
  
  
  CONCLUSIONS
  Only drugs that affect cholinergic function have shown consistent, but modest, clinical effects, even in late-phase trials. There is a need for a better appreciation of the various risk factors and drug targets for the treatment of AD. The wide range of targets makes it unlikely that affecting only 1 of those targets (eg, cholinergic function or N-methyl-d-aspartate) will lead to a more than minimally effective treatment option, regardless of when a treatment is started and discontinued. There is substantial opportunity for the continued growth and development of drugs and clinical trial expansion for the treatment of AD.
authors.affiliation: Pharmacy Practice, University of Connecticut, Storrs, Connecticut. Electronic address: ehret@uchc.edu.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Ehret
authors.affiliation: Pharmacy Practice, University of Connecticut, Storrs, Connecticut.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Chamberlin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D000077265:Donepezil; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D000068836:Rivastigmine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine; D008559:Memantine
keywords: Alzheimer disease; Phase III; donepezil; galantamine; memantine; rivastigmine