Memantine is beneficial for the treatment of patients with Alzheimer disease (AD), according to the results of an open-label extension trial reported in the January issue of the Archives of Neurology.

"Memantine treatment resulted in significant benefits compared with placebo in global, functional, and cognitive assessments," write Barry Reisberg, MD, from the New York University School of Medicine in New York, and colleagues. "In addition, memantine treatment of patients with moderate to severe AD receiving stable doses of donepezil was found to be safe and efficacious. Memantine treatment has also shown cognitive benefit in clinical studies on mild to moderate vascular dementia and efficacy in a study on patients who were severely demented and institutionalized."

The initial study was a 28-week, randomized, double-blind, placebo-controlled trial of memantine, 20 mg daily, in 252 patients with moderate to severe AD. In this open-label, 24-week extension trial, 175 outpatients were continued from the previous double-blind study, and raters remained blind to the patients' initial study treatment. Efficacy assessments from the original study were continued and safety parameters were monitored. ç

The completion rate for the extension trial was 78%. Patients who switched to memantine from placebo had a significant benefit in functional, global, and cognitive efficacy assessments compared with their mean rate of decline during placebo treatment (P < .05). For the patients who were randomized to memantine treatment during the double-blind phase, these clinically relevant benefits also appeared to be maintained. The favorable adverse event profile for memantine was similar to that seen in the double-blind study.

"These results extend previous findings that demonstrated the efficacy and safety of memantine in the treatment of patients with moderate to severe AD," the authors write. "Memantine treatment was safe and well tolerated during the course of the study."

Merz Pharmaceuticals funded this study and employs 2 of its authors. Some of the authors have disclosed various relevant financial relationships with Merz Pharmaceuticals; Lundbeck; Forest Laboratories, the maker of memantine; Pfizer; and/or Wyeth.

In an accompanying editorial, Jeffrey L. Cummings, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, discusses the implications of these findings for memantine, for clinical trials, and for drug development for AD.

"These new data from Reisberg and coworkers provide additional reassurance to prescribing physicians that long-term use of memantine is safe, continues to have a low rate of adverse effects, and may have continuing beneficial clinical effects," Dr. Cummings writes. "Each trial contributes to our understanding of optimal ways of conducting drug development programs for this important disorder of the elderly. The stage is set for the advent of a new generation of therapies with disease-modifying properties."

Dr. Cummings has disclosed relevant financial relationships with AstraZeneca, Avanir, Bristol Myers-Squibb, Eisai Forest, Janssen, Lilly, Lundbeck, Memory, Merz, Neurochem, Novartis, Ono, Pfizer, Praecis, Takeda, Sanofi-Aventis, Sepracor, and Wyeth. Dr. Cummings is supported by the National Institute on Aging, the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation.