Medicines commonly used to treat epilepsy and other seizure disorders appear to be effective at soothing the agitation in people with Alzheimer's disease and other forms of dementia. The findings are a glimmer of good news for the treatment of some of the most disturbing aspects of the disease, which afflicts about 4 million people in the United States alone.
The results by University of Rochester scientists are being featured at a media briefing this week at the 6th International Conference on Alzheimer's Disease and Related Disorders in Amsterdam, the Netherlands.
Psychiatrists Pierre Tariot and Anton Porsteinsson, physicians at the University's main Alzheimer's treatment site at nearby Monroe Community Hospital, presented the results from several placebo-controlled studies showing that the compounds are effective in treating agitation among patients with dementia. The medicines appear to be as good as or better than the medicines physicians have available now to treat agitation, says Tariot. Patients' aggression and agitation are often the top concerns among families of patients, say physicians.
"The behavioral disturbances wear care givers down and are one of the main reasons that patients are admitted to acute and long-term care institutions," says Porsteinsson. "People don't put their husbands or mothers in nursing homes because they are forgetful; they're put in a nursing home because they are a danger to themselves or others, or because they're unbearably hostile or aggressive. This type of medicine alleviates those symptoms for many patients in a population that is a bear to treat."
About three-quarters of patients on the medicine carbamazepine improved in two of the studies, which were funded by the National Institutes of Health. The second study, with 51 patients, was halted prematurely because the drug appeared so effective that physicians concluded that further enrollment was not necessary and that all patients should have access to it.
Agitation is one of many symptoms that patients with Alzheimer's and other dementias develop as their brain cells get sick and die. The patients' memory and comprehension deteriorate, they become confused and disoriented, and ordinary tasks become impossible. Nine out of 10 patients have significant behavioral problems at some point, says Tariot, professor of psychiatry and neurology and director of the University's Program in Neurobehavioral Therapeutics at Monroe Community Hospital. There is no single best treatment for agitation, he says. Doctors have used sedatives and anti-psychotic drugs like haloperidol and thioridazine in the past, with only limited success.
Some doctors have previously reported case studies where anti-seizure medicines like carbamazepine seemed to improve Alzheimer's patients' symptoms. Doctors normally use the medicines to treat epilepsy and help patients control impulses or aggression similar to that seen in most Alzheimer's patients; use of the medications to treat dementia is growing as clinicians see the benefit.
"This is a case where medical science is trying to catch up with clinical practice," says Porsteinsson, an assistant professor of psychiatry. "The medicines are already being used, but there haven't been studies in place to determine just how safe and effective these agents are. That's what our work is all about." The team's studies are the first placebo-controlled trials of anti-seizure medications in the treatment of Alzheimer's disease.
Nurses measured behaviors like tension, hostility, and aggression -- screaming and yelling, hitting or spitting at care givers, verbally abusing them, throwing things, pacing, and other inappropriate actions. The nurses, who didn't know which patients were on placebo and which were receiving the medicine, watched and spoke with the patients and their care givers in nursing homes around Rochester. Doctors analyzing the results found that patients on the medicine were less aggressive and agitated, and nursing aides said those patients were more engaged in social activities and required less time to manage.
The team also presented preliminary results from a small, placebo-controlled pilot study of divalproex sodium, another common anti-seizure medication. The results of the study, sponsored by the Alzheimer's Association, are promising enough to spur a large multi-center trial, says Tariot. He is principal investigator of one such study that is just beginning; that study is being funded by Abbott Laboratories, which markets divalproex sodium under the brand name Depakote. A similar large study is being considered by the National Institute on Aging.
The Rochester team has pioneered the use of anti-seizure medications like carbamazepine and divalproex to treat Alzheimer's and also has expertise in studying and treating nursing home residents. "A nursing home is like a laboratory in which to study dementia in its worst form," says Tariot, who estimates that about three-quarters of nursing home residents have dementia, most from Alzheimer's disease.
Tariot's research group of about 20 doctors, nurses, and other staff is currently conducting about 20 studies with approximately 225 patients. The carbamazepine and divalproex studies included patients from Monroe Community Hospital, St. John's Home, the Jewish Home, St. Ann's Home, the Highlands Living Center, and the Veterans Administration Medical Center in Canandaigua. At the outpatient clinic at Monroe Community Hospital, the team treats an additional 400 patients on an ongoing basis.
"The field is evolving very rapidly," says Tariot, who is leading a symposium on treatment of behavioral disorders and dementia at the Amsterdam meeting. "Six years ago, there was nothing to treat Alzheimer's disease. Now, we have two FDA-approved drugs and as many as a dozen more coming out within five years. We're even talking about prevention strategies. It's very exciting and gratifying."