Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study)

Geriatr Gerontol Int. 2017 Mar;17(3):494-499. doi: 10.1111/ggi.12754. Epub 2016 Apr 25.


Aim: Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients.

Methods: This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms.

Results: Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms.

Conclusions: In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499.

Keywords: Alzheimer's disease; agitation; memantine; rivastigmine patch.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Factor Analysis, Statistical
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Memantine / administration & dosage*
  • Memantine / adverse effects
  • Multivariate Analysis
  • Prospective Studies
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / etiology
  • Psychomotor Agitation / physiopathology*
  • Republic of Korea
  • Risk Assessment
  • Rivastigmine / administration & dosage*
  • Rivastigmine / adverse effects
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome


  • Rivastigmine
  • Memantine