Alzheimer’s Disease Reisberg et al.
In a 28-week, randomized, double-blind, parallel-group study, Reisberg and colleagues evaluated the efficacy of memantine in patients with probable moderate-to-severe AD. The investigators confirmed the diagnosis of AD using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria; the Mini-Mental Status State Examination (MMSE) scores of 3 to 14; and the Global Deterioration Scale (GDS), stage 5 or 6.
Overall, 252 patients were randomly assigned to receive either memantine 20 mg/day or an equivalent placebo. The memantine patients received an initial dose of 5 mg once daily, followed by an escalating regimen of 5 mg weekly, to a dose of 10 mg twice daily. The assessments and observations of the patients were made at the baseline evaluation, at 12 weeks, and at 28 weeks.
The Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) score, the Alzheimer’s Disease Cooperation Study-Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev) score, and the Severe Impairment Battery (SIB) score were used to evaluate the efficacy of the therapy. The CIBIC-Plus measured overall global change on a scale of 1 (markedly improved) to 7 (markedly worse). The ADCS-ADLsev measured functional capacity on a scale of 0 to 54 (with 54 representing optimal performance). The SIB evaluated the cognitive performance on a scale of zero (0) to 100 (with 0 representing the greatest impairment).
At 28 weeks, the analysis of change in scores from baseline showed a statistically significant improvement in favor of memantine therapy compared with placebo. The memantine group experienced better outcomes (i.e., less deterioration), according to the mean change in CIBIC-Plus (P = .06 with the last observation carried forward [LOCF] and P = .03 for the observed cases), the ADCS-ADLsev (P = .02 with the LOCF and P = .003 for the observed cases), and the SIB (P < .001 with the LOCF and P = .002 for the observed cases). However, no significant differences were observed for the MMSE, Global Deterioration Scale stage, or Neuropsychiatric Inventory assessments between the actively treated and the placebo-treated patients. canadian antibiotics
Ferris et al.
In an extension phase of the 28-week study, 175 patients who completed the previous double-blind study were given an open-label treatment with memantine for another 24 weeks. The CIBIC-Plus, ADCS-ADL, and SIB scales were used to measure the efficacy variables.
The patients who had previously been given placebo and who were switched to memantine therapy improved in terms of the projected rate of continued decline. Memantine was also well tolerated, and there were no important differences in adverse drug effects (ADEs) between patients who switched from placebo to memantine and those who continued memantine therapy. The overall findings supported the long-term use of meman-tine in patients with moderate-to-severe AD.
Farlow et al.
In another randomized, 24-week, double-blind, placebo-controlled trial, researchers recruited 403 patients with moderate-to-severe AD who had also been taking the cholinesterase inhibitor for at least six months and who achieved stabilization by taking the same dose for at least three months.
The patients were randomly assigned to receive 10 mg of memantine twice daily or an identical placebo. The mem-antine group initially received 5 mg daily; this amount was increased weekly by 5 mg to achieve the dose of 20 mg/day (10 mg twice daily). The primary efficacy assessments were analyzed by the SIB, the ADCS-ADL, and the CIBIC-Plus.
At week 24, statistically significant improvement (P < 0.001) in cognitive function, as measured by the SIB, was observed in patients taking the combination of donepezil and memantine. The mean difference in the change in SIB scores for the combination group taking memantine and donepezil, compared with the patients receiving placebo and donepezil, was 3.3 units.
At week 24, the patients receiving combination therapy experienced significantly improved daily functioning according to the ADCS-ADL evaluation (P = .028) compared with the patients receiving placebo.
At the end of the study, the mean difference in ADCS-ADL scores was 1.6 units. The CIBIC-Plus global assessment also showed statistically significant results (P = .027) in favor of the combined memantine/donepezil therapy. This trial demonstrated the superior efficacy of memantine, combined with canadian donepezil, in treating moderate-to-severe AD over that of donepezil alone.
Vascular Dementia Wilcock et al.
The efficacy, tolerability, and safety of memantine was evaluated in a 28-week, double-blind study in patients with mild-to-moderate vascular dementia. A total of 579 patients completed a two-week washout period with placebo, followed by the randomization schedule of either 20 mg of memantine or placebo. Therapy was begun with an initial dose of 5 mg daily, which was escalated by 5 mg weekly to a final dose of 20 mg daily.
The investigators evaluated the primary efficacy variables using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinical Global Impression of Change (CGI-C). The ADAS-Cog, a quantitative instrument that assesses the severity of cognitive impairment over time, consists of 11 tests, including word recall, naming objects and counting fingers, and word recognition. The CGI-C shows the change of clinical status from baseline values. Secondary efficacy variables included the Nurses’ Observation Scale for Geriatric Patients (NOSGER), the Gottfries-Brane-Steen Scale (GBS) score, and the MMSE score.
Patients in the memantine group showed significant improvement in ADAS-Cog total scores compared with the placebo group. The mean difference between the groups was 1.75 (P= .0005). At the end of the 28 weeks, there was no significant difference in CGI-C values between the groups (P = .1103). The NOSGER assessment, which included a rating of memory, indicated higher memory scores (by 0.72 points) in patients taking memantine (P = 0.02). All other secondary efficacy scores showed no significant difference between the two treatment groups.
In general, treatment with memantine resulted in significant improvement in the cognitive performance in patients with vascular dementia.