Benefits of extended-release Memantine (28 mg, Once Daily) on Caregiver Distress: results of a multinational, double-blind, placebo-controlled trial in moderate to Severe Alzheimer’s Disease

GEORGE GROSSBERG; FACUNDO MANES; RICARDO ALLEGRI; LUIS MIGUEL GUTIERREZ ROBLEDO; SERGIO GLOGER; LIE XIE; DANIEL JIA; JAMES PERHACH; MICHAEL TOCCO; STEPHEN GRAHAM

Toronto

Encuentro; 62nd AAN 2010 Annual Meeting; 2010

American Academy of Neurology

OBJECTIVE: Post hoc evaluation of caregiver distress related to neuropsychiatric symptoms in patients with Alzheimer's disease (AD) treated with extended-release (ER) memantine. BACKGROUND: Memantine is approved for the treatment of moderate to severe AD; in the US, the recommended dosage of the currently approved immediate-release formulation is 10 mg, twice daily (20 mg/day). We recently evaluated the safety, tolerability, and efficacy of a once-daily ER formulation (28 mg/day) in outpatients with moderate to severe AD, receiving stable cholinesterase inhibitor (ChEI) treatment. Top-line results, reported previously, showed significant benefits of memantine ER over placebo in alleviating neuropsychiatric symptoms. DESIGN/METHODS: All patients completed a 2-week, single-blind, placebo-only period, followed by a 24-week period of double-blind treatment with memantine ER (28 mg) or placebo. Caregiver distress was assessed using the Neuropsychiatric Inventory - Caregiver Distress Scale (NPI-D). Baseline-to-Endpoint changes of the total NPI-D score and individual item scores, calculated using the last observation carried forward (LOCF) and observed cases (OC) approaches, were analyzed by means of an ANCOVA model with treatment group and study center as factors, and with baseline values as covariates. RESULTS: A total of 677 patients (mean MMSE 10.8 [range 3-17]) were randomized to receive memantine ER (n=342) or placebo (n=335). At study Endpoint, caregivers of patients in the memantine/ChEI group reported a reduction in overall caregiver distress (NPI-D total score), compared to caregivers of patients receiving placebo/ChEI (OC: P=0.038; LOCF: P=0.054). Individual items showing significant differences between groups at Endpoint were agitation/aggression (OC, LOCF), irritability/lability (OC), and nighttime behavior (LOCF), all in favor of memantine ER treatment. CONCLUSIONS/RELEVANCE: Caregivers of patients treated with memantine ER (28 mg) reported significantly less emotional distress with respect to patients' behaviors compared to caregivers of patients treated with placebo. These reports of decreased distress are consistent with the behavioral benefits observed in memantine-treated patients, reported previously. Supported by: Forest Laboratories, Inc.