Why ketamine is a speedster antidepressant: Study is first to identify how it works; could be adapted for use without its many side effects

Ketamine is the speedster of antidepressants, working within hours compared to more common antidepressants that can take several weeks. But ketamine can only be given for a limited amount of time because of its many side effects.

Now, a new Northwestern Medicine study identifies for the first time exactly how ketamine works so quickly, and how it might be adapted for use as a drug without the side effects.

The study in mice shows ketamine works as a rapid antidepressant by increasing the activity of the very small number of newborn neurons, which are part of an ongoing neurogenesis in the brain.

New neurons are always being made at a slow rate. It’s been known that increasing the number of neurons leads to behavioral changes. Other antidepressants work by increasing the rate of neurogenesis, in other words, increasing the number of neurons. But this takes weeks to happen.

By contrast, ketamine produces behavioral changes simply by increasing the activity of the existing new neurons. This can happen immediately when the cells are activated by ketamine.

“We narrowed down the population of cells to a small window that is involved,” said lead study author Dr. John Kessler, a professor of neurology at Northwestern University Feinberg School of Medicine and the Ken and Ruth Davee Professor of Stem Cell Biology. “That’s important because when you give ketamine to patients now, it affects multiple regions of the brain and causes a lot of adverse side effects. But since we now know exactly which cells we want to target, we can design drugs to focus only on those cells.”

The side effects of ketamine include blurred or double vision, nausea, vomiting, insomnia, drowsiness and addiction.

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