FDA Highlights: Could anti-depressant citalopram affect development of Alzheimer’s?

by Bruce Sylvester – The selective serotonin reuptake inhibitor (SSRI) citalopram appears to impede development of amyloid beta, a plaque-forming peptide in the brain believed to be involved in the onset of Alzheimer’s disease.

The findings emerged from studies of the effect of the SSRI on brain interstitial fluid of plaque-bearing mice and cerebrospinal fluid of healthy humans. They appear in the May 14, 2014 issue of Science Translational Medicine.

“Our previous studies have shown an association between anti-depressants and the reduction in amyloid burden in the brain,” said lead author, Yvette Sheline, MD, professor of Psychiatry, Radiology and Neurology and director of the Center for Neuromodulation in Depression and Stress, at The University of Pennsylvania Perlman School of Medicine in Philadelphia.

She added, “Those studies examined a retrospective correlation between the duration of anti-depressant use and amyloid burden shown in PET scans in the brains of elderly volunteers. With this new study we took our research a step further and tested the prospective effect of the SSRI citalopram on the CSF amyloid levels in younger, healthy subjects.”  Sheline undertook the new research while associated with Washington University School of Medicine in St. Louis.

The researchers found that the level of amyloid-beta in the interstitial fluid of transgenic plaque-bearing mice decreased in a dose-dependent manner by as much as 25 percent compared to baseline. And, notably, after two months of citalopram exposure the mice showed no new plaque development, and no growth of existing plaques.

Citalopram did not induce any significant regression of pre-existing amyloid plaques.

In a parallel study, double-blind study, 23 healthy human subjects, age 18 to 50 (with no medical disease and no previous history of anti-depressant use) received 60 mg/day citalopram.  There was also a control group using a placebo.

The researchers reported that, among the treated subjects, citalopram exposure led to a 38 percent lower A-beta concentration over the 37-hour period compared to placebo subjects, as well as a drop in newly-produced A-beta in the citalopram-treated group.

“While these results are an excellent start at lowering A-beta production, we are a long way from making a statement regarding the ability of SSRIs to prevent the cognitive decline associated with AD,” Sheline said. “We are developing a greater understanding of the capabilities of SSRIs, which offer promise for the future as preventive measures, as we continue to uncover the complex mechanisms in the brain that trigger Alzheimer’s and dementia.”