Ketamine: Quick Relief for Depression

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MunichCommon medications fail in just over one in three people with depression. It has been known for some time that the anesthetic ketamine can help them - much faster than an antidepressant. If it takes weeks for them to take effect, ketamine administered intravenously takes a few hours. But there is one major catch - ketamine has serious side effects. It triggers hallucinations in some patients.

Researchers led by Christoph Turck from the Max Planck Institute for Psychiatry in Munich have now found out how the antidepressant effect of the substance comes about. To do this, they tested the effect of ketamine in the hippocampus of mice.

The hippocampus is a brain region that is important for memory. It has long been known that its function is impaired in people with depression. This is also expressed in the fact that they are less able to remember things.

Altered cell metabolism

In fact, the energy metabolism in the cells of the hippocampus changed after the administration of ketamine - within two hours. Instead of obtaining energy primarily through so-called glycolysis - in which only blood sugar is processed - energy production shifts towards the citric acid cycle due to the influence of the ketamine, the researchers found.

Using this mechanism, the cell's energy power stations, the mitochondria, can process not only sugar, but also protein and fat. This type of energy generation is much more effective. Therefore, under the influence of ketamine, the cells have more energy available.

“Such changes, such as B. glycolysis and the citric acid cycle, along with disorders of the mitochondria, were previously associated with depression, ”explains Katja Weckmann, doctoral student and first author of the study.

Refreshed nerve cells

And ketamine has another positive effect: It promotes the formation of fresh proteins on the branches of the nerve cells, the synapses.

"All of these observations could explain the faster effects of ketamine compared to common antidepressants," says Turck. On the basis of the findings, the researchers hope, it would be possible to create drugs that are as effective as ketamine, but work without the dreaded side effects. (cf)

Source: Weckmann K et al: Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates, Translational Psychiatry, 2014.

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