Progress Made in Understanding How Selective Serotonin-Reuptake Inhibitors (SSRIs) Work to Ease Depression

Some highly effective medications also happen to be highly mysterious. Such is the case with the antidepressant drugs known as selective serotonin re-uptake inhibitors, or SSRIs: They are the most common treatment for major depression and have been around for more than 40 years, yet scientists still do not know exactly how they work. Nor is it known why only two out of every three patients respond to SSRI treatment, or why it typically takes several weeks for the drugs to take effect—a significant shortcoming when you’re dealing with a disabling mood disorder that can lead to impaired sleep, loss of appetite, and even suicide. New research by a team of Rockefeller University scientists helps elucidate how SSRIs combat depression. Their work, published online on May 21, 2020 in Molecular Psychiatry (, could one day make it possible to predict who will respond to SSRIs and who will not, and to reduce the amount of time it takes for the drugs to act. The open-access article is titled “AP-1 Controls the p11-Dependent Antidepressant Response.” Major depression—also known as clinical depression—is firmly rooted in biology and biochemistry. The brains of people who suffer from the disease show low levels of certain neurotransmitters, the chemical messengers that allow neurons to communicate with one another. And studies have linked depression to changes in brain volume and impaired neural circuitry.
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