Ketamine helps with resistant depression. And now we know why

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Ketamine acts quickly and works in cases resistant to first-line drugs, SSRIs. Now a study in Nature seems to have identified the mechanism that explains its effectiveness. The discovery may lead to new drugs that are as effective as ketamine but with less risk of addiction.

It works in a few hours, when it normally takes weeks before you can experience positive effects, and it works in the most difficult cases. We are talking about ketamine, the drug with many uses with analgesic, anesthetic and psychogenic action, which has recently proved to be a powerful antidepressant (it is the active ingredient of esketamine nasal spray for the treatment of major depression approved last year by the FDA and EMA ). But the mechanism that determines its antidepressant efficacy had not yet been fully understood. The gap is now filled by a study in Nature which has reconstructed the process by which ketamine changes mood learn more.

It all depends on the role of a group of proteins called 4E-BP involved in the formation of memory. At least so the experiments on mice show. The researchers observed the effect of ketamine on the behavior and neuronal activity of mice from which 4E-BP proteins had been removed by genetic editing techniques. In animals with this deficiency, ketamine did not perform its antidepressant action.

The 4E-BP proteins act as a switch that turns on or off the protein synthesis process essential for memory formation.

These proteins affect the activity of two main types of neurotransmitters, excitatory ones, which make up the majority of neurons in specific portions of the brain, and inhibitor ones, which regulate excitatory neurons and have significant impacts on attitude. The disposal of 4E-BP from the inhibitory cells was adequate to obstruct the impact of ketamine. Ketamine has established itself on the antidepressant drug scene as a breakthrough in the treatment of psychiatric disorder. 30 percent of patients are resistant to first-line drugs (selective serotonin reuptake inhibitors SSR1), and subanesthetic doses of ketamine provide rapid and long-lasting antidepressant effects. But there’s the other side of the coin: Ketamine is addictive.

The researchers hope their findings pave the way for better, safer, and lower risk of addiction antidepressant therapies for patients with major depressive disorder. “Too many decisions continue to be made using a trial and error approach that can prolong patients’ suffering and affect their quality of life. Our finding has the possibility to push us nearer to the examination for a safer choice to ketamine and, finally, to a characterized medical technique, in which medical treatments are tailored to the individual characteristics of each patient, ”says Aguilar-Valles. the authors of the study.

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