December 29, 2008
People in the advanced stages of Alzheimer's disease may benefit from the drug galantamine, according to a large new study from Europe. But while the drug appeared to be safe in an elderly population with severe Alzheimer's who were living in nursing homes, the benefits were generally modest at best.
Galantamine is sold under the brand name Razadyne in the United States, and was formerly called Reminyl. It is usually prescribed to slow the progression of symptoms in those with mild to moderate Alzheimer's, with drug treatment discontinued once symptoms become severe. But this study suggests that Razadyne is safe and may produce modest improvements in cognitive function in men and women with advanced dementia as well.
The trial, known as the SERAD study, was carried out in 57 medical centers in 10 European countries. The findings appeared in the British medical journal The Lancet Neurology.
Razadyne is known as an acetylcholinesterase inhibitor, a family of drugs that increases levels of a brain chemical called acetylcholine. Other drugs in the class include Aricept (donepizel) and Exelon (rivastigmine), and doctors commonly prescribe them for people with mild to moderate disease.
Other studies have shown that cognitive function may improve in some patients with severe dementia who took Aricept. Any benefits, however, are usually modest at best, and improvements last for only a limited period.
Any medication that can help to slow the inevitable decline can help keep patients out of nursing homes and help to reduce the financial burden of providing adequate care.
In the current study, researchers recruited more than 400 elderly patients, most in their 80s, who were living in nursing homes. All had severe Alzheimer's, as determined by a standardized test known as the mini-mental state examination. Many also suffered from other diseases, or comorbidities, like heart disease or diabetes. None were taking other medications for Alzheimer's, including cholinesterate inhibitors or memantine (Namenda), another drug often given for the more moderate to severe stages of Alzheimer's.
In the study, about half were given Razadyne, while the others took a look-alike placebo. The patients who were taking Razadyne scored higher on assessments of memory and some tests of physical and thinking abilities, although the results were not dramatic. Side effects of the drug were also mild and generally tolerable in these elderly men and women. However, while patients taking Razadyne scored higher in some measures, their caretakers did not rate them as better able to carry out everyday tasks like bathing and dressing and getting about.
"The data show that there are untreated patients with severe Alzheimer's disease in nursing homes who could benefit from starting treatment with galantamine," the authors wrote. The results, they concluded, "extend the efficacy range of galantamine from patients with mild to moderate and advanced moderate into severe Alzheimer's…and show that galantamine can be started and used safely, with good tolerability, in a group of patients with severe Alzheimer's disease and comorbidities," or other ailments.
In an editorial accompanying the study, Dr. Martin Farlow of the Indiana University School of Medicine agreed that Razadyne was safe in this elderly population with advanced Alzheimer's but cautions that "the clinical usefulness of galantamine has still not been proven in this population." Results were only modest, and most of the patients were not able to better carry out everyday tasks of living. He calls for longer studies that use different methods to measure activities of daily living to assess the efficacy of the drug in people with severe disease.
Dr. Farlow notes that current clinical guidelines call for starting patients on a cholinesterase inhibitor during the early to middle stages of Alzheimer's, rather than late in the course of the disease, as was done in this trial. Starting Razadyne late in the course of Alzheimer's"might not be the same as the continuation of long-term treatment" with the drug, he notes.
He also calls for additional study to assess the effects of using galantamine, too, in patients with severe disease who are already taking Namenda. "Whether galantamine might or might not continue to provide clinical benefits to such patients will, again, require longer-term trials or trials of adding galantamine to pre-existing memantine therapy," he states.
While any drug benefits can be helpful, the study underlines the importance of continued research into the underlying causes of Alzheimer's and the need for better, more effective, treatments. The Fisher Center for Alzheimer's Research Foundation continues to fund vital research into the causes of Alzheimer's and the search for a cure. To learn more, visit www.ALZinfo.org.
Alistair Burns, Roberto Bernabei, Roger Bullock, et al: "Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trial." The Lancet Neurology, published online, December 1, 2008.
Martin R. Farlow, Indiana University Schoolof Medicine, "Reflection and Reaction: The SERAD Study of the Safety and Efficacy of Galantamine in Severe Alzheimer's Disease."