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Alzheimer's Troubling Behaviors Hard to Treat

Available medications inadequate for disturbing symptoms

TUESDAY, Feb. 1, 2005 (HealthDayNews) -- Along with devastating memory loss, Alzheimer's disease can trigger such hard-to-manage behaviors as aggression, wandering, hallucinations and repetitive vocalizations.

The bad news for caregivers is that available medications do little to help control such problems, which affect up to 80 percent of those who get Alzheimer's, reports a new study in the Feb. 2 issue of the Journal of the American Medical Association.

"Alzheimer's caregivers are often looking for a magic pill. They want us to treat the problem and make it go away," said study author Dr. Kaycee Sink, a geriatric medicine specialist at Wake Forest University Baptist Medical Center.

"Alzheimer's is a complicated disease, and every person has unique characteristics," she said. "It may not be realistic to expect that one drug will work for every person or behavioral symptom."

In other words, "there is no magic pill," she added.

"When you look across the issues that affect patients and families, behavioral problems tend to have a very special place," said William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.

"In dealing with the memory problems associated with Alzheimer's, people find ways to manage. But behavioral problems tend to be particularly disturbing for caregivers, and it's often the behavioral symptoms that drive placement into a nursing home," he added.

Sink and her colleagues searched several large medical literature databases to find randomized, placebo-controlled clinical trials of medications used to treat behavioral symptoms in people with Alzheimer's.

Twenty-nine studies matched their criteria. The studies looked at 15 different medications, including typical and atypical antipsychotics, antidepressants, mood stabilizers, cholinesterase inhibitors and memantine.

The studies that looked at the efficacy of antipsychotic medications, antidepressants and mood stabilizers included mostly people who were living in nursing homes. The studies evaluating cholinesterase inhibitors and memantine included mostly people still living at home.

"We found that there weren't very many effective treatments for dementia-related behavioral symptoms," said Sink.

Based on the trials, Sink said it was clear that unless the people with Alzheimer's disease had depression, antidepressant medications generally weren't effective. Mood stabilizers also weren't found to be effective in treating behavioral problems.

Overall, typical antipsychotic medications, such as haloperidol and thioridazine, achieved a slight benefit, but side effects were common. Some atypical antipsychotics, such as olanzapine and resperidone, showed a statistically significant effect, but Sink said she wasn't sure if this effect would be strong enough to be meaningful for a patient or caregiver. Also, the risk of stroke was increased with these medications.

The analysis also included two studies on memantine, a relatively new drug for treating Alzheimer's. But their results were inconclusive: One study showed no benefit, and the other showed a statistically significant benefit, but many of those in the placebo arm of that trial worsened.

There were eight trials of cholinesterase inhibitors included and, as with memantine, results were mixed or inconclusive. One drug, metrifonate, was effective but never received government approval because it had severe side effects. Other cholinesterase inhibitors showed small improvements over placebos, but again Sink cautioned these results might not be clinically meaningful.

"None of the drugs we're using are very effective. We need to focus attention on non-pharmaceutical trials, and perhaps investigate the use of other drug therapies and combine them with non-drug approaches," Sink said.

Alzheimer's experts agreed with her conclusions.

"The overall effect of the agents we have available to treat behavioral symptoms are of limited use," said Dr. John C. Morris, director of the Alzheimer's Disease Research Center at Washington University in St. Louis. "It's not that they don't work, but the degree to which they work is suboptimal. We definitely need better drugs."

One reason these drugs may not work well in people with Alzheimer's, according to Morris, is that they're simply not designed to specifically treat Alzheimer's. For example, antipsychotic medications may be very useful in treating hallucinations in someone with schizophrenia, but that same medication doesn't work well for someone with Alzheimer's disease.

While the symptoms may look the same, the underlying cause may differ, Morris explained.

Despite what would seem glum news, both Sink and Morris think caregivers do have options.

All patients first need to be assessed to make sure there are no underlying conditions causing the behavior, Morris said, and then if medication is needed, it should be started at the lowest dose possible and gradually increased. Also, he added, once the behavior is gone, patients should be gradually taken off medications.

There are non-drug therapies that may be useful also, such as music therapy and pet therapy. But, Morris said one of the most helpful strategies is caregiver education.

"If a caregiver understands what a provoking incident may be, they may be able to come up with solutions," he said.

And Thies added that it's important to remember that "there's no one-size-fits-all approach."

More information

The Alzheimer's Association offers these tips for preventing Alzheimer's disease.

SOURCES: Kaycee Sink, M.D., assistant professor, medicine in gerontology and geriatric medicine, Wake Forest University Baptist Medical Center, Winston-Salem, N.C.; William Thies, Ph.D., vice president, medical and scientific affairs, Alzheimer's Association, Chicago; John C. Morris, M.D., Board of Directors, Alzheimer's Association, and director and principal investigator, Alzheimer's Disease Research Center, Washington University, St. Louis; Feb. 2, 2005, Journal of the American Medical Association
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