Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis

Int J Neuropsychopharmacol. 2014 Dec 28;18(5):pyu115. doi: 10.1093/ijnp/pyu115.

Abstract

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease.

Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects.

Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects.

Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.

Keywords: Alzheimer’s disease; cholinesterase inhibitors; memantine; meta-analysis; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Activities of Daily Living / psychology*
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Antiparkinson Agents / therapeutic use
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition / drug effects*
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Male
  • Memantine / administration & dosage
  • Memantine / adverse effects
  • Memantine / therapeutic use*
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Cholinesterase Inhibitors
  • Memantine