Memantine in Moderate to Severe Alzheimer’s Disease: a Meta-Analysis of Randomised Clinical Trials

Abstract

The efficacy of memantine in Alzheimer’s disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status (Clinician’s Interview-Based Impression of Change Plus Caregiver Input), cognition (Alzheimer’s Disease Assessment Scale – Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer’s Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (without replacement of missing values) showed statistically significant effects for memantine (vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine’s clinically relevant efficacy in patients with moderate to severe AD.

Medications used in dementia: a review of evidence

“…A metaanalysis done in 2007 of six individual phase III studies using a subgroup of patients with moderate to severe AD showed that the drug resulted in a statistically significant benefit in four domains: namely cognitive, functional, global, and behavioural domains. The metaanalysis also highlighted a significant improvement in ADL with memantine, compared to placebo (22). A metaanalysis in 2011 found no significant differences between memantine and placebo on any outcome for patients with mild AD, either on individual trial or when data were combined (ADAS-cog 0.17; P = 0.82) (25).…”

“…A number-needed-to-treat (NNT) analysis of memantine Medications used in dementia: a review of evidence showed a NNT of 3-8 (19). It is indicated for the treatment of moderate to severe AD, and has shown significant efficacy in improving symptoms in several large-scale, controlled clinical studies (20)(21)(22)(23). Memantine may be effective in delaying worsening of clinical symptoms, and decreasing the emergence of BPSD (24)(25).…”

Long-Term Effects Of Combined Treatment With Memantine And Donepezil On Alzheimer's Disease Patients: 72-Week Study

“…A review of published clinical trials of memantine indicated that early treatment of hypertension, a risk factor for stroke, reduces the risk of vascular dementia and slows its progression [39]. In addition, a previous study showed that memantine may be effective in improving the memory of patients with MCI [40].…”

Alzheimer’s Disease: New Diagnostic Criteria and Therapeutic Aspects Depending on the Stage of the Disease

“…Донепезилу была свойственна более высокая частота побочных эффектов по сравнению с плацебо (особенно связанных с дисфунк-цией желудочно-кишечного тракта), и соответственно пре-парат чаще отменялся по данной причине [10,15]. Трехлетняя открытая фаза двух клинических испытаний мемантина у пациентов с умеренной и тяжелой деменци-ей при БА показала, что на фоне длительной терапии мемантином происходит практически двукратное замед-ление нарастания когнитивных нарушений [37,38].…”