The Efficacy and Safety of Memantine for the Treatment of Alzheimer's Disease

Expert Opin Drug Saf. 2018 Oct;17(10):1053-1061. doi: 10.1080/14740338.2018.1524870. Epub 2018 Sep 26.


Currently, five pharmacotherapeutic options are available to treat Alzheimer's disease: memantine; the three cholinesterase inhibitors donepezil, galantamine, and rivastigmine; and combination treatments with memantine and one cholinesterase inhibitor. Selection of the best course of treatment is based upon the evidence gathered by systematic reviews and meta-analyses of randomized controlled trials. Areas covered: This article provides a risk-benefit analysis of these treatments using evidence from meta-analyses on their safety and their efficacy. Expert opinion: Memantine improves cognitive functions and behavioral disturbances more efficiently than the placebo, both as monotherapy and in combination with donepezil. Although memantine monotherapy and combination therapy are associated with a few individual adverse events such as somnolence, it is well-tolerated and its safety (all-cause discontinuation) is comparable or superior to that of the placebo (agitation). Pooled cholinesterase inhibitors are superior to the placebo in the improvement of cognitive functions, but not behavioral disturbances and they are not well-tolerated, as evaluated by the high discontinuation rate. Donepezil (10 mg/day) and oral rivastigmine and galantamine monotherapies carry the risk for some adverse events including gastrointestinal symptoms. Therefore, we consider that combined treatment with memantine and donepezil is the most useful treatment for Alzheimer's disease.

Keywords: All-cause discontinuation; Alzheimer’s disease; memantine; meta-analysis; safety outcomes; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / adverse effects
  • Cognition / drug effects
  • Donepezil
  • Drug Therapy, Combination
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Excitatory Amino Acid Antagonists / adverse effects
  • Humans
  • Indans / administration & dosage
  • Indans / adverse effects
  • Memantine / administration & dosage*
  • Memantine / adverse effects
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Randomized Controlled Trials as Topic


  • Cholinesterase Inhibitors
  • Excitatory Amino Acid Antagonists
  • Indans
  • Piperidines
  • Donepezil
  • Memantine