Memantine Helps Prevent Agitation, Aggressive Behavior in Moderate-to-Severe AD, Improves Appetite

Internal Medicine World ReportNovember 2005

Memantine Helps Prevent Agitation, Aggressive Behavior in Moderate-to-Severe AD, Improves Appetite

By John Schieszer

SAN DIEGO—Agitation and aggressive behavior are common characteristics afflicting patients with Alzheimer’s disease (AD), features that add to the difficulties of managing patients with the disease as well as complicate the lives of those caring for the patients.

Findings from a recent study presented at the annual meeting of the American Association of Geriatric Psychiatry suggest that memantine (Namenda) therapy may significantly reduce agitation or aggression as well as improve appetite in patients with moderate-to-severe AD who are already receiving stable doses of donepezil (Aricept). In addition, memantine has been shown to lessen the risk that agitation and aggression will develop in asymptomatic patients.

Investigators at the University of California Los Angeles (UCLA) looked at data from 404 patients who were treated at 37 different sites. At 24 weeks, memantine treatment resulted in a significantly greater percentage of patients remaining asymptomatic on the individual domains of a rating scale measuring agitation/aggression, irritability/ability, and nighttime behavior than those receiving placebo.

In addition, when patients who were symptomatic at baseline were examined, there was significantly less worsening compared with placebo in symptoms of agitation/aggression and appetite/eating changes.

“We showed that memantine reduced agitation when measures are taken at 12 and 24 weeks into a study. Agitation is very common in Alzheimer’s disease, and reducing agitation is important for the patient and the caregiver,” said lead investigator Jeffrey Cummings, MD, director, Alzheimer’s Disease Center, UCLA.

Data were analyzed from a 24-week, double-blind, placebo-controlled trial conducted with moderate-to-severe AD patients (mean age, 76 years) who were receiving stable donepezil treatment; nearly two thirds of the patients were women. Results of the study showed significant benefits with memantine on functional, cognitive, and global measures. Behavioral symptoms were assessed using the Neuropsychiatric Inventory (NPI), which was administered at baseline and at weeks 12 and 24.

All the patients were treated with memantine, 10 mg twice/day (titrated in 5-mg weekly increments from a starting dose of 5 mg/d during week 1, to 20 mg/d at the beginning of week 4), or placebo. In addition, patients were treated with at least 6 months of ongoing daily donepezil monotherapy at a stable dose (5 or 10 mg/d) for the immediate preceding 3 months and throughout the study period. Baseline characteristics between the placebo and memantine groups were comparable.

At 24 weeks, there was a significant treatment difference, with fewer behavioral disturbances and psychiatric symptoms in memantine-treated patients, while these symptoms worsened in patients receiving placebo. Several NPI domains demonstrated statistically significant treatment differences in favor of memantine at week 24.

“We did not anticipate that memantine was going to have a behavioral benefit, so this was an unexpected outcome of the trial,” Dr Cummings toldIMWR. “The side effects that are seen tend to be things like headache or dizziness and were at a level not very much greater than placebo. It has been an easy drug to use.”

George Grossberg, MD, professor of geriatrics at St. Louis University School of Medicine, commented that these findings are good news for patients. “It is important because it may help keep patients out of nursing homes and also improve their quality of life,” he said.

Memantine is an N-methyl-D[sm cap d]-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate-to-severe AD. It blocks prolonged pathologic activation of NMDA receptors, which may explain its beneficial impact on agitation and excitability. It is believed that excitotoxicity mediated by NMDA receptors plays a role in the pathogenesis of AD.

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