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).
OBJECTIVE
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.
Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea.
Soo J
SJ
Yoon
Department of Neurology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.
Seong H
SH
Choi
Department of Neurology, Bobath Memorial Hospital, Seongnam-si, Korea.
Hae R
HR
Na
Department of Neurology, Dong-A Medical Center, Dong-A University College of Medicine, Busan, Korea.
Kyung-Won
KW
Park
Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan, Korea.
Eun-Joo
EJ
Kim
Department of Neurology, Myongji Hospital, Seonam University of College of Medicine, Goyang, Korea.
Hyun J
HJ
Han
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Bucheon, Korea.
Jae-Hong
JH
Lee
Department of Neurology, Bucheon St. Mary's Hospital, The Catholic University College of Medicine, Bucheon, Korea.
Young S
YS
Shim
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Duk L
DL
Na
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005163:Factor Analysis, Statistical; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects; D015999:Multivariate Analysis; D011446:Prospective Studies; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D056910:Republic of Korea; D018570:Risk Assessment; D000068836:Rivastigmine / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000068836:Rivastigmine; D008559:Memantine
Alzheimer's disease; agitation; memantine; rivastigmine patch