Cognitive Benefits of Galantamine Sustained During Long-term Use

Laurie Barclay, MD

February 20, 2004

Feb. 20, 2004 — Galantamine may slow clinical progression of Alzheimer disease (AD) during 36 months of continuous use, according to the results of an open-label extension study published in the February issue of the Archives of Neurology.

"AD causes progressive cognitive and functional decline over years. Although cholinesterase inhibitors (AChEIs) have demonstrated efficacy in studies lasting three to six months, little is known about long-term therapy," write Murray A. Raskind, MD, from the University of Washington School of Medicine in Seattle, and colleagues. "Galantamine hydrobromide (Reminyl), the most recently approved AChEI, exhibits a dual mechanism of action: competitive acetylcholinesterase inhibition and nicotinic receptor modulation."

In this study, 194 U.S. patients with mild to moderate AD who had been randomized to continuous galantamine therapy in either of two double-blind, placebo-controlled trials subsequently received continuous galantamine therapy for up to 36 months. Using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS), the investigators compared changes from baseline (at study enrollment) in this group with those in a clinically similar historical control sample of AD patients who had received placebo for 12 months, and with the mathematically predicted decline of untreated patients over 36 months.

The mean ADAS cognitive subscale score increased by 10.2 ± 0.9 points in patients treated continuously with galantamine for 36 months. This cognitive decline was approximately half of that predicted for untreated patients. Almost 80% of patients who continued galantamine therapy for up to 36 months had apparent benefits in cognitive function compared with that predicted for untreated patients.

In 75 patients who discontinued galantamine therapy before 36 months, rate of decline before discontinuation was similar to that in patients who completed 36 months of treatment. The drug was safe and well tolerated throughout the study period.

"Although these results suggest long-term positive effects on clinical decline in AD patients treated with galantamine, conclusions are limited by the lack of biological indicators of disease progression and the absence of a true long-term placebo control group," the authors write. "Even more convincing demonstrations of disease-modifying effects of AChEIs hopefully will emerge from ongoing placebo-controlled trials in persons with mild cognitive impairment."

Johnson & Johnson Pharmaceutical Research and Development employs two of the study authors and Janssen Pharmaceutica employs one of the authors. Dr. Raskind has financial arrangements with Forest Laboratories, Janssen Pharmaceutica, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, and Novartis.

Arch Neurol. 2004;61:252-256

Reviewed by Gary D. Vogin, MD