Penn research finds antidepressants may reduce signs of Alzheimer’s

Perhaps there is a silver lining in this depressing year of coronavirus, natural disasters, and social upheaval.

A new study from a Penn researcher adds to evidence that a class of antidepressant drugs known as SSRIs may reduce production of a key protein found in the brains of people with Alzheimer’s disease. This is evidence, she said, that the drugs could someday be part of a cocktail used to prevent or delay this form of dementia.

“I certainly wouldn’t argue that people should convince themselves that they should start taking SSRIs for this reason,” said Yvette Sheline, author of the study published this month in the journal Neurology.

On the other hand, if you’re already taking SSRIs (selective serotonin reuptake inhibitors), this may be an added reason to feel comfortable with your choice. “Maybe it’s a twofer,” said Sheline, a psychiatrist who directs Penn’s Center for Neuromodulation in Depression and Stress.

Americans have reported worsening mental health during the pandemic. A study earlier this year found that prescriptions for drugs used to treat anxiety and depression had increased.

Sheline’s team looked at how doses of escitalopram (Lexapro) affected levels of the protein amyloid in the spinal fluid of healthy adults aged 50 and up. Participants did not have symptoms of dementia or serious depression. Previous work had found decreased levels of the protein in younger adults who took the drug.

Abnormal clumps of amyloid in the brain are a hallmark pathological sign of Alzheimer’s disease.

After two to eight weeks of treatment, participants who took the drug had 9.4% less spinal fluid amyloid than those who took a placebo. Sheline said that was not enough time for thinking ability to be affected, so that wasn’t measured. She said it is likely that people who took the drug longer would have a larger cumulative effect.

Sheline readily concedes that this is “very complicated” terrain. People with depression are at higher risk for dementia and vice versa. And, once clumps of Alzheimer’s start forming in the brain, the amount of amyloid in spinal fluid actually lessens. While it is clear that amyloid accumulates in Alzheimer’s, scientists are still sorting out whether the protein causes dementia or is a byproduct of other processes that damage the brain.

“I certainly don’t think that amyloid alone is responsible for Alzheimer’s disease, but I think it is definitely involved,” Sheline said. Tangles of another protein, tau, are also found in the deadly degenerative disease and are more closely correlated with disability.

Sheline started this line of research a decade ago after discovering that, contrary to her expectations, some people with depression had less amyloid in their brains than she had expected. She began looking at medication use and found a connection between antidepressants and lower brain amyloid.

That led to a series of studies that added to the evidence. Some involved John Cirrito, an expert on mouse models of Alzheimer’s disease at Washington University School of Medicine. The animal work found that injecting the animals with SSRIs lowered both levels of amyloid in brain fluids and clumps of amyloid.

While all the participants in the most recent Penn study had normal scores on cognitive tests, some had abnormally low amyloid levels in their spinal fluid, a sign that they may already have had amyloid clumping in their brains. (This study did not do brain images.) Those participants did not respond as much to the escitalopram as those who started with normal amyloid levels. This could mean, Sheline said, that the drug would need to be started early.

Sheline said she has no immediate plans for follow-up studies. “I’m waiting for something else that will be the next step,” she said.