Antidepressants could delay Alzheimer's, according to Penn Prof.

Citalopram and its cousin escitalopram are two of the most commonly prescribed antidepressants for people beginning treatment for depression. But recent studies indicate that they might have a second use — delaying Alzheimer’s.

When Perelman School of Medicine professor Yvette Sheline studied the brains of people with a history of depression who had taken antidepressant medications, she noticed something surprising — they had significantly lower levels of amyloid protein.

The brains of Alzheimer’s patients have significantly higher levels of amyloid plaques, clusters of protein fragments that build up between nerve cells. Preventing or destroying those plaques, or the amyloid beta fragments that form them, are major areas in Alzheimer’s research.

As she tried to determine what was behind the link, Sheline began to focus on a specific set of antidepressants called Selective Serotonin Reuptake Inhibitors, or SSRIs. SSRIs include some of the best known antidepressants — like Prozac, Zoloft and citalopram and escitalopram, sold under the brand names Celexa and Lexapro. Because their side effects are fairly low and are well-documented, they are often the first antidepressants doctors will prescribe to a patient.

“We’re doing this study in order to try to provide evidence that the common SSRI antidepressants have an additional mechanism of action, which is to lower the amyloid concentration in the cerebral spinal fluid,” Sheline said.

SSRIs increase activation of receptors for the neurotransmitter serotonin, which is frequently associated with depression. But it has another effect: Studies have indicated that serotonin also decreases the production of amyloid beta, reducing the number of plaques that form. In a 2014 paper, Sheline found that SSRIs caused a 37 percent decrease in production of amyloid beta in healthy humans.

Sheline’s current study focuses on people between 65 and 85 years of age, who will each get either an active drug or a sugar pill placebo. Each patient will receive a spinal tap before and after the treatment. Sheline hopes to expand to a larger study if her results look promising.

“It would be a preventative treatment,” she said. “We don’t think this is going to treat people with Alzheimer’s, but...even if it can only delay the onset of Alzheimer’s, that’s a pretty major thing to aim for.”