title: Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis.
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.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. shinjim@fujita-hu.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D002800:Cholinesterase Inhibitors; D008559:Memantine
keywords: Alzheimer’s disease; cholinesterase inhibitors; memantine; meta-analysis; systematic review