title: Tolerability and efficacy of memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer's disease: a multicenter, randomized, open-label, parallel-group study.
abstract: OBJECTIVE
  To compare the tolerability and efficacy of combination therapy of memantine plus rivastigmine patch with rivastigmine patch monotherapy in patients with mild to moderate Alzheimer's disease (AD).
  
  
  METHODS
  In this multicenter, randomized, open-label study, patients entered an 8-week run-in period (a 5 cm 2 rivastigmine patch for 4 weeks, then a 10 cm(2) patch for 4 weeks) followed by 16 weeks of memantine plus rivastigmine patch or rivastigmine patch monotherapy. The primary outcome measure was the retention rate at the end of the trial.
  
  
  BACKGROUND
  clinicaltrials.gov. NCT01025466.
  
  
  RESULTS
  Overall, 88 and 84 patients received rivastigmine patch with and without memantine, respectively, and of these, 77 (87.5%) and 70 (83.3%) patients completed the study. The difference in retention rate was not significant (95% confidence interval: -6.3-14.7%). The incidence of adverse events (AEs) (53.4 vs. 50.6%) and discontinuation due to AEs (6.8 vs. 4.8%) were not different between patients with and without memantine. The most frequent AEs were skin irritation in patients with and without memantine (42.0 vs. 34.9%, p = 0.71), but discontinuation due to skin irritation was rare (4.5 vs. 2.4%, p = 0.74). The incidence of gastrointestinal AEs was very low in patients with and without memantine (nausea, 2.3 vs. 1.2%; vomiting, 1.1 vs. 1.2%). The Korean Version of the Cohen Mansfield Agitation Inventory scores favored rivastigmine patch monotherapy at the end of treatment (p = 0.01). Changes in other efficacy measures were similar between the groups.
  
  
  CONCLUSIONS
  There were no significant differences in tolerability and safety between the treatment groups. The combination therapy of memantine plus rivastigmine patch did not show an advantage over rivastigmine patch monotherapy on efficacy analyses. The sample size for comparing tolerability may have been too small to detect a difference of efficacy between the two groups.
authors.affiliation: Department of Neurology, Inha University School of Medicine, Incheon, South Korea.
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Park
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Han
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
authors.forename: Yong S
authors.initials: YS
authors.lastname: Shim
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000009:adverse effects; D000068836:Rivastigmine; D012720:Severity of Illness Index; D057968:Transdermal Patch; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine; D008559:Memantine