In a new study, researchers found why in low doses, the anesthetic drug ketamine could have a rapid effect on difficult-to-treat depression.
They identified a key target for the drug: specific serotonin receptors in the brain. The findings offer the hope of new, more effective antidepressants.
The research was conducted by a team at Karolinska Institutet.
Depression is the most common psychiatric diagnosis in Sweden, affecting one in 10 men and one in five women at some point during their lives.
Between 15 and 30% of patients are not helped by the first two attempts at therapy, in which case, depression is designated difficult to treat.
Studies have shown that low doses of the anesthetic drug ketamine act rapidly on certain sufferers, but exactly how it works is unknown.
A nasal spray containing ketamine has recently been approved in the U.S. and EU for patients with treatment-resistant depression.
In the study, the team imaged the brains of study participants using a positron emission tomography (PET) camera in connection with ketamine treatment.
In the first phase of the study, 30 people with difficult-to-treat depression were randomly assigned to either a ketamine-infusion group (20 individuals) or a placebo (saline) group.
The participants’ brains were imaged with a PET camera before the infusion and 24-72 hours afterward.
In the next phase, those who so wished (29 individuals) received ketamine twice a week for two weeks.
The result was that over 70% of those treated with ketamine responded to the drug according to a rating scale for depression.
Serotonin plays a key role in depression and low levels are thought to be linked to more serious diseases. There are 14 different kinds of receptors for this neurotransmitter on the surface of neurons.
For their PET imaging, the researchers used a radioactive marker that binds specifically to serotonin 1B receptors.
They found that the ketamine operated via these receptors in a formerly unknown mechanism of action.
Binding to this receptor reduces the release of serotonin but increases that of another neurotransmitter called dopamine.
Dopamine is part of the brain’s reward system and helps people to experience positive feelings about life, something that is often lacking in depression.
The team says that ketamine treatment increases the number of serotonin 1B receptors.
Ketamine has the advantage of being very rapid-acting, but at the same time, it is a narcotic-classed drug that can lead to addiction.
The lead author of the study is Mikael Tiger, a researcher at the Department of Clinical Neuroscience, Karolinska Institutet.
The study is published in Translational Psychiatry.
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