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Am Fam Physician. 2004;70(5):963

Memantine was recently approved by the U.S. Food and Drug Administration for the treatment of moderate to severe Alzheimer’s disease. It is the first drug in a new class calledN-methyl-d-aspartate (NMDA) receptor antagonist. Tariot and colleagues assessed the clinical efficacy, safety, and tolerability of memantine in patients on a stable regimen of donepezil therapy.

In this double-blinded, multicenter trial, 203 participants with moderate to severe Alzheimer’s disease were randomized to receive treatment with memantine for 24 weeks, following a one- or two-week single-blinded lead-in period, and 201 received placebo. All patients had been taking a stable dosage of donepezil for at least six months at entry and were required to continue this baseline drug for the duration of the trial.

Outcome measures included cognition, function, and global performance, as measured by the Severe Impairment Battery (SIB) and a modified AD Cooperative Study—Activities of Daily Living Inventory (ADCS—ADL). Secondary outcome measures included performance on additional rating scales: the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory (NPI), and the Behavioral Rating Scale for Geriatric Patients (BGP).

Significantly more patients completed the memantine arm of the study than the placebo arm. There was a statistically significant improvement in patients taking memantine in both primary outcomes. The mean CIBIC-Plus score was significantly better in the memantine group, and 55 percent of the patients taking memantine were rated as improved or unchanged compared with 45 percent of the placebo group. There were fewer behavioral disturbances and psychiatric symptoms, as measured by the NPI score, in the patients taking memantine. In addition, the BGP dependency subscale was significantly improved with memantine use. More participants in the placebo group discontinued therapy because of adverse effects. The adverse effect most often associated with discontinuation was confusion.

The authors conclude that the efficacy of memantine is significantly better than that of placebo in the treatment of moderate to severe Alzheimer’s disease in patients taking stable dosages of donepezil, as measured by cognitive function, activities of daily living, behavior, and clinical global status.

editor’s note: Memantine can be an expensive option. A recent review found that memantine, in dosages of 20 mg per day, had beneficial effects on cognition and function but not on clinical impression of change when compared with placebo.1 The clinical impression of change is considered an essential adjunct to basic cognitive and functional scales. However, because most of the health care costs of Alzheimer’s disease relate to advanced disease, memantine may be cost-effective even if the absolute clinical benefits are small.2—c.w.

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