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Clinical and Research News
Geriatric Psychiatrists Encouraged By New Alzheimer’s Drug
Psychiatric News
Volume 39 Number 6 page 58-77

It was formally the subject of at least four new research poster presentations and one formal industry-supported symposium. But formal presentation or not, memantine (Namenda)—Forest Laboratories’ newly launched novel medication for the treatment of Alzheimer’s disease (AD)—was the topic to talk about during last month’s 17th Annual Meeting of the American Association for Geriatric Psychiatry (AAGP).

The drug came up in numerous informal conversations, symposia sponsored by competing products’ manufacturers, and countless other sessions. And it managed to do so without an overly large presence of representatives from Forest—most of the marketing team was said to be busy elsewhere, preparing for the drug’s launch the same week as the AAGP meeting.

Simply put, the drug’s apparent popularity and seeming importance are based on this simple fact: memantine is the first truly new treatment for patients with Alzheimer’s in over a decade. The first of the cholinesterase inhibitors, tacrine (Cognex), debuted in September 1993, followed by three "me too" drugs: donepezil (Aricept) in 1996, rivastigmine (Exelon) in 2000, and galantamine (Reminyl) in 2001.

Memantine, however, is thought to block the N-methyl-D-aspartate (NMDA) receptor, one of two receptors in the brain that normally bind glutamate. The NMDA receptor is thought to mediate certain aspects of learning and memory. As receptor activity increases, those memory processes are inhibited. By blocking NMDA receptor activity, memantine is thought to improve those learning and memory processes.

The FDA approved memantine in October 2003 for the treatment of moderate-to-severe Alzheimer’s.

Four studies with memantine were presented as new research posters at the AAGP meeting.

Perhaps the most intriguing was the poster by Elaine Peskind, M.D., and her colleagues. Peskind, a professor of psychiatry at the University of Washington, Seattle, oversaw an industry-funded multicenter, randomized, clinical trial of memantine in patients with mild-to-moderate Alzheimer’s. Her results suggest that memantine’s ability to significantly delay the decline in cognitive abilities will benefit not only patients with more severe disease, but also those with less-advanced Alzheimer’s.

Peskind and her colleagues enrolled 403 patients (both men and women) over the age of 50 with a diagnosis of probable Alzheimer’s who had an MRI or CAT scan consistent with probable Alzheimer’s and a Mini-Mental State Exam score between 10 and 22. Patients were randomized to memantine 10 mg twice a day or to placebo and followed for 24 weeks.

All patients were given the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician’s Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus). The ADAS-cog, rarely used in the clinical setting, is a standardized clinical trial measure of seven cognitive domains, with a total score ranging from zero to 70. Higher scores denote worse cognitive function. The CIBIC-Plus is an expanded, clinician-rated, interview-based scale similar to the Clinical Global Impression.

Over the course of 24 weeks, those patients taking memantine 10 mg twice a day actually experienced small but significant improvements in cognition, measured by the ADAS-cog, and remained improved compared with baseline at 24 weeks.

In contrast, patients receiving placebo experienced small but significant steady declines in cognitive function over the 24-week study. Peskind and other researchers hope the delay in decline will translate into delaying a patient’s institutionalization. A delay in placing an Alzheimer’s patient in a nursing home can drastically affect the individual, his or her family, and finances. With average costs of nursing home care running $7,000 a month nationally, even a three-month delay could save a patient $21,000.

Peskind notes that because memantine "has a distinctly novel mechanism of action and very few side effects, it provides physicians, caregivers, and patients a completely different treatment option for moderate-to-severe Alzheimer’s now, and hopefully for patients with mild-to-moderate Alzheimer’s in the future."

Based on Peskind’s results and other data, Forest announced an intention to file a Supplemental New Drug Application with the FDA by this summer for approval of memantine in patients with mild-to-moderate Alzheimer’s.

The most common treatment-emergent side effects noted in pooled analysis of all the clinical trials with memantine include confusion and headache. Interestingly, agitation, depression, accidental injury, and urinary and upper-respiratory-tract infections were all significantly lower in patients taking memantine compared with those taking placebo. ▪

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