Abstract
OBJECTIVE: We assessed the effects of adding memantine to stable cholinesterase inhibitor (ChEI) therapy on neuropsychiatric symptoms in moderate to severe Alzheimer’s disease (AD). BACKGROUND: Neuropsychiatric symptoms are common in moderate to severe AD and associated with caregiving burden; most patients experience several of them at any point in time. Antipsychotics, often used to manage individual symptoms, carry safety risks. Clinical-trial evidence indicates that memantine/ChEI combinations are superior to monotherapy with either drug. DESIGN/METHODS: Data from patients with moderate to severe AD (N=1,140) were pooled from three 24-week, randomized, placebo-controlled trials of memantine added to stable ChEI therapy. Neuropsychiatric symptoms were assessed using the 12-item Neuropsychiatric Inventory (NPI). Total and single-item score changes from baseline at week 24 in all patients and those symptomatic at baseline (total NPI score 蠅1; n=939) were analyzed via ANCOVA (intent-to-treat population, observed cases; α=0.05). Percentages of patients asymptomatic at baseline and at week 24 (total/item NPI score =0) were compared using Fisher’s exact test (α=0.05). RESULTS: At week 24, memantine/ChEI-treated patients significantly outperformed placebo/ChEI-treated patients on the NPI total score (all patients: P=0.001; symptomatic subset: P=0.003) and on the items of agitation (all: P<0.001; symptomatic: P=0.019), appetite/eating change (symptomatic: P=0.037), delusion (all: P=0.038; symptomatic: P=0.039), disinhibition (all: P=0.057; symptomatic: P=0.0497), irritability/lability (all: P=0.009; symptomatic: P=0.055), and nighttime behavior (all: P=0.0495). The percentages of patients who were asymptomatic at both baseline and week 24 on total NPI were not significantly different between groups (memantine/ChEI: 5.6[percnt]; placebo/ChEI: 3.5[percnt], P=0.119). CONCLUSIONS: These results suggest that adding memantine to stable ChEI therapy in individuals with moderate to severe AD may confer benefits in various neuropsychiatric symptoms. Study Supported by: Forest Laboratories, LLC, a subsidiary of Actavis, Inc.