Common SSRI antidepressant also reduces neurotoxins related to dementia

The commonly prescribed antidepressant escitalopram (Lexapro^®) also lowers levels of neurotoxic metabolites that can cause memory loss and dementia, according to findings from a study published in the Journal of Psychiatric Research. The study also showed depression is associated with a pro-inflammatory state.

The researchers concluded that escitalopram treats depression in part by inhibiting certain neurotoxic metabolites and perhaps also in part by reducing the inflammatory response.

In this small study, researchers recruited 27 healthy subjects and 30 severely depressed patients who were treated with escitalopram for the 12-week study period. Baseline plasma samples showed that the depressed patients had significantly higher levels of pro-inflammatory biomarkers (hsCRP, TNFα, IL6, and MCP1), along with an elevated level of an anti-inflammatory cytokine (IL10). These findings indicate an inflammatory response with an immune system reaction.

Depression can trigger an inflammatory response that in turn can exacerbate depression, causing a vicious cycle, said the study’s lead author Angelos Halaris, MD, PhD, Professor in the Department of Psychiatry and Behavioral Neurosciences at Loyola University Chicago Stritch School of Medicine, in Maywood, IL.

“It behooves us to diagnose depression early, treat it vigorously to achieve remission, and work to prevent its relapse,” Dr. Halaris said.

Of the 20 patients in the treatment group who completed the study, 80% reported complete or partial relief from their depression.

The researchers also found that levels of two neurotoxic metabolites dropped significantly in treated patients. Levels of 3-hydroxykynurenine (3HK) fell by more than two-thirds between week 8 and week 12; and levels of quinolinic acid (QUIN) dropped 50% during the first 8 weeks and were lower at the end of the study than at the beginning.

In addition to these findings, the researchers also identified—for the first time—correlations between specific depressive symptoms and certain biomarkers, “but these correlations must be viewed as very preliminary,” the authors cautioned. Depressed mood correlated significantly with IFNγ, while weight loss correlated significantly with TNFα levels. QUIN correlated significantly with guilt, and QUIN/3HK correlated significantly with guilt and psychomotor agitation.

The pro-inflammatory biomarkers that were elevated at baseline had not significantly decreased in treated patients by the end of the study, but the researchers surmised that inflammation may take more than the 12 weeks of this study to re-normalize. Therefore, they called for further studies that involve larger patient cohorts over a longer course of time.

Additional research could also include other SSRI antidepressants besides escitalopram—such as Prozac®, Paxil®, and Zoloft®—to determine if these also protect against neurotoxins, Dr. Halaris said.