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.
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"Memantine is licensed for treatment of moderate-tosevere Alzheimer's disease (AD) (Areosa et al. 2005). Efficacy in patients with moderate-to-severe AD was demonstrated in a meta-analysis of six randomized placebo-controlled trials showing modest beneficial effects on global status and cognition after treatment with memantine (Winblad et al. 2007). Memantine has a favorable safety and tolerability profile (Farlow et al. 2008). "
[Show abstract][Hide abstract]ABSTRACT: Background: Augmentation of clozapine with memantine targets altered glutamatergic neurotransmission in schizophrenia and showed beneficial effects on several symptom domains in a small proof-of-concept study. In this second study we report the effects of memantine add-on treatment to clozapine for cognitive disturbances and negative and positive symptoms in schizophrenia.
Method: Patients with clozapine-resistant schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (N=26) or placebo (N=26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on the Cambridge Neuropsychological Test Automated Battery, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale. Secondary endpoints were change on the Calgary Depression Scale for Schizophrenia, Yale-Brown Obsessive Compulsive Scale, Health of the Nation Outcome Scales (HoNOS), Manchester Short Assessment of Quality of Life, and Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS).
Results: When compared with placebo, memantine improved verbal recognition memory (free recall; ES=0.56), paired associates learning (ES=0.40), PANSS negative subscale score (ES=0.29), and HoNOS symptoms (ES=0.33). Memantine treatment was associated with a higher score on the Allergic Reactions subscale of the LUNSERS (ES=0.44).
Conclusion: In patients with clozapine-resistant schizophrenia, treatment with adjunctive memantine significantly improved visual and verbal memory and negative symptoms without serious adverse effects.
Trial Registration: ISRCTN14760638 (doi: 10.1186/ISRCTN14760638)
Full-text · Article · Feb 2016 · Psychological Medicine
"Memantine displays an excellent tolerability profile in this patient population, with one meta-analysis of six trials finding a lower overall rate of premature discontinuation with memantine treatment compared with placebo (18 vs. 23 %) . Memantine also showed fewer discontinuations because of AEs compared with placebo (odds ratio of 0.80) . The use of memantine in combination with a ChEI has been examined in many randomized controlled trials [65– 70]. "
[Show abstract][Hide abstract]ABSTRACT: Current pharmacological therapy for Alzheimer's disease (AD) includes the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine, and galantamine and the N-methyl D-aspartate receptor antagonist memantine. Based on the results of randomized controlled trials and several meta-analyses, ChEIs appear to show modest but statistically significant improvements on several measures, including cognition and global functioning. Given their modest effects, there is a lack of consensus among clinicians regarding issues related to initiation, optimal duration, and discontinuation of ChEI therapy across the spectrum of AD. There is evidence from long-term observational controlled studies that early initiation and persistent exposure to AD therapy lead to delays in nursing home admission and significantly slower rates of cognitive and functional impairment. In the moderate to severe stages of AD, therapeutic trials of higher dose ChEIs and the addition of memantine are recommended for patients who are no longer responding to lower doses. While side effects are generally mild and gastrointestinal in nature, these events can lead to significant morbidity in more susceptible patients with advanced disease. Patients should thus be regularly monitored for any potential serious side effects of ChEI therapy, which also may include syncope and bradycardia. At the terminal stages of AD, such as when patients become hospice eligible, attempts to cautiously discontinue all medications not necessary for quality of life, including AD drugs, should be made.
"NMDARs are which are involved in various intracellular cascades and participate in several functions associated with synaptic plasticity and pathological conditions are composed of at least seven subunits, these include a ubiquitously expressed NR1 This is a Post-print of published article: Amini, E., Rezaei, M., Ibrahim, N. M., Golpich, M., Ghasemi, R., Mohamed, subunit, four distinct NR2 subunits (named as NR2A, NR2B, NR2C and NR2D) and two NR3 subunits (NR3A and NR3B) [90,91]. NMDAR activation may be an important mechanism in the pathogenesis of a wide range of neuropathological disorders including schizophrenia, stroke, depression, multiple sclerosis, Huntington's disease , Parkinson's disease , Alzheimer's disease [94,95], and epilepsy [96,92]. Several surveys have displayed a differentially increased expression of NR2B in the hippocampus of patients with epilepsy [ "