Could antidepressants prevent Alzheimer's?

As surprising as it may seem, a University of Pennsylvania psychiatrist thinks antidepressants might help prevent Alzheimer's disease.

Yvette Sheline, who runs Penn's Center for Neuromodulation in Depression and Stress, expected to head down a completely different path when she started studying the relationship between depression and how much amyloid people had in their brains in 2009.

Depression is common in people in the early stages of dementia. People with a history of depression have long been considered at higher risk for developing thinking and memory problems in late life, possibly because chronic stress damages part of the brain, Sheline said. It's also related to heart disease, which is itself a risk factor for dementia.

Amyloid beta is one of the key proteins that create the plaques that build up in the brains of people with Alzheimer's disease.

Sheline, who studied a group of cognitively normal people, thought she would see more amyloid in the brains of those with a history of depression. Instead, she found that depressed people who had taken antidepressants had significantly less amyloid accumulation than seen in non-depressed people. Further, the more antidepressants people had taken, the lower the levels, Sheline found.

Intrigued, she went on to study mice. She found that there was less amyloid in fluid in their brains after they were given selective serotonin reuptake inhibitor (SSRI) antidepressants. There was also less amyloid accumulation in the brains of mice chronically treated with the antidepressant citalopram.

After that, she conducted a study in a small group of young, healthy people. She found that a dose of citalopram reduced the amount of amyloid in cerebrospinal fluid by 38 percent.

What this all means is unclear. The precise role of amyloid - Is it a cause of disability or a symptom of some other problem? - remains unproven. Several trials are underway to test whether drugs that target amyloid can delay or prevent the onset of Alzheimer's. Earlier trials were disappointing, but they involved patients who already were sick.

Many treatments that have looked promising against Alzheimer's in early studies have ultimately failed to change the course of the deadly disease.

In Sheline's new trial, study subjects will take the antidepressant escitalopram (Lexapro) for eight weeks. Researchers will then analyze their spinal fluid.

Sheline's hope is that the results will give her enough ammunition to get a grant for a larger, longer trial that would measure amyloid deposition using PET scans in people at risk for Alzheimer's disease. Because the drug she is using is already generic, she said, this kind of testing is "not going to be developed by the pharmaceutical companies."

She said she is interested in looking at antidepressants for dementia because they are already FDA approved and have few side effects. The most common side effect is gastrointestinal upset.

Little previous work has been done on this relationship. David Weisman, an Abington neurologist who is involved in several Alzheimer's clinical trials, said he was unaware of research on antidepressants and progression of dementia.

However, he said that nothing currently works to slow down the disease. Even if SSRIs had a small effect, they are considered "very safe."

The drugs are often used to treat symptoms of early Alzheimer's. They "can help drastically with early symptoms like anxiety, depression, apathy, and sometimes even irritability and anger," he said.

Carol Lippa, director of the Memory and Cognitive Disorders Program at Drexel Neurosciences Institute, was skeptical that a reduction in the type of amyloid Sheline is measuring would translate into real patient benefits. She also pointed to studies finding that another SSRI did not improve symptoms of depression in dementia patients.

"These medications all can have side effects and interactions, so taking them should not be done lightly," Lippa wrote in an email. "In sum, it is an interesting idea, though there is no evidence that it would impact the symptoms patients suffer."

Sheline said SSRI's are not likely to have a big effect on Alzheimer's, but slower progression could be valuable.

"If I could get Alzheimer's at 85 instead of 80, I'd take it," Sheline said.

She is more than halfway through recruiting for the current trial, but eager for more study subjects.

Jill Bellas and her husband, Jim, both signed up after hearing a radio report about the trial. Jill Bellas, 76, lost both her mother and her younger sister to Alzheimer's.

"I just wanted to do something," said Bellas, who lives in West Chester. "There's a guilt for being skipped over. I just want to help in any way I can because this horrible thing has got to be stopped."

Neither she nor her husband was told whether they got the study drug or placebo and she has heard no results. She had some side effects, but it didn't affect her mood. "I'm like a really happy person anyway," she said.

Sheline said she doesn't take the drug and wouldn't recommend that others do it in the hope of preventing dementia.

"At the point when we show that it actually changes amyloid bonding, I will," she said. "There isn't enough evidence at this point to recommend anything like that."

For more information about the trial, call 215-746-2637, email CNDSlab@mailmed.upenn.edu or go to clinicaltrials.gov and enter "Sheline" in the search field.

sburling@phillynews.com
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