In a new study from Karolinska Institutet, researchers found that the anesthetic ketamine can help people with severe depression has raised hopes of finding new treatment options for the disease.
They found novel mechanistic insights into how the drug exerts its antidepressant effect.
According to the World Health Organization, depression is a leading cause of disability worldwide and the disease affects more than 360 million people every year.
The risk of suffering is affected by both genetics and environmental factors. The most commonly prescribed antidepressants, such as SSRIs, affect nerve signaling via monoamines in the brain.
However, it can take a long time for these drugs to help, and over 30 percent of sufferers experience no relief at all.
The need for new types of antidepressants with faster action and wider effect is therefore considerable.
An important breakthrough is the anesthetic ketamine, which has been registered for some years in the form of a nasal spray for the treatment of intractable depression.
Unlike classic antidepressants, ketamine affects the nerve signaling that occurs via the glutamate system, but it is unclear exactly how the antidepressant effect is mediated. When the medicine has an effect, it relieves depressive symptoms and suicidal thoughts very quickly.
However, ketamine can cause unwanted side effects such as hallucinations and delusions and there may be a risk of abuse so alternative medicines are needed.
In the study, the team aimed to better understand how ketamine works in order to find substances that can have the same rapid effect but without the side effects.
They examined the molecular mechanisms underlying ketamine’s antidepressant effects.
Using experiments on both cells and mice, the researchers were able to show that ketamine reduced so-called presynaptic activity and the persistent release of the neurotransmitter glutamate.
Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine.
The researchers were able to see that ketamine directly stimulated AMPA receptors, and this leads to the increased release of the neurotransmitter that inhibits glutamate release.
This suggests that the antidepressant action of ketamine can be regulated by a feedback mechanism. It is new knowledge that can explain some of the rapid effects of ketamine.
If you care about depression, please read studies about people with depression lack this stuff in the brain to fight chronic stress and findings of your walking speed may show your dementia and depression risks.
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The study is published in the journal Molecular Psychiatry. One author of the study is Per Svenningsson.
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