Good news! More research confirming the potential for ketamine to be a potentially effective treatment for depression!
I have blogged here and here about ketamine before. Ketamine appears to be less addictive than other treatments.
Unfortunately, the regulatory government bureaucracy will most likely and unnecessarily delay the new treatment to become widely available anytime soon.
"... Two years later [2019], the arrival of the first ketamine-based antidepressant – the nasal spray esketamine, made by Johnson & Johnson – was applauded as the most exciting development in the treatment of mood disorders in decades. Yet the U.S. Food and Drug Administration still limits the spray’s use. It is mainly given to depressed patients who have not been helped by other therapies ...
there have been no major breakthroughs in the treatment of depression since the 1987 approval of the most famous antidepressant of all time, Prozac. ...
Meanwhile, existing drugs bring no relief to about a third of depressed patients. Even when the drugs do work, they take four to eight weeks to take effect, a delay that can prove fatal in suicidal cases. ...
They [ketamine] make people feel better within hours. Their antidepressant action then lasts for days after the drug itself has cleared from the body. Evidently, it’s the body’s response to ketamine, rather than ketamine itself ...
In this study ... mapped out gene expression in thousands of individual neurons in the brains of mice that had been given a dose of ketamine. These neurons belong to networks that convey their signals by means of the neurotransmitter glutamate. Ketamine had been known since the 1990s to produce its effects by acting on such neurons – this in contrast to older antidepressants, which mainly affect neurons influenced by serotonin. But since ketamine’s effect persists long after it leaves the body, its action could not be explained by mere blockage of glutamate receptors on the surfaces of neurons. ...
To this end, the scientists focused on the ventral hippocampus ... After mapping out gene expression in cells from this area of the mouse brain, the researchers identified a subpopulation of neurons with a characteristic genetic signature. Ketamine had increased these neurons’ expression of a gene called Kcnq2, which encodes a potassium channel – ... In a series of elaborate experiments on the molecular and cellular levels, which included electrophysiological, pharmacological, behavioral and functional studies, the scientists confirmed their major finding: Ketamine exerts its lasting antidepressant effect by enhancing the Kcnq2 potassium channels in a certain subtype of glutamate-sensitive neurons. ..."
there have been no major breakthroughs in the treatment of depression since the 1987 approval of the most famous antidepressant of all time, Prozac. ...
Meanwhile, existing drugs bring no relief to about a third of depressed patients. Even when the drugs do work, they take four to eight weeks to take effect, a delay that can prove fatal in suicidal cases. ...
They [ketamine] make people feel better within hours. Their antidepressant action then lasts for days after the drug itself has cleared from the body. Evidently, it’s the body’s response to ketamine, rather than ketamine itself ...
In this study ... mapped out gene expression in thousands of individual neurons in the brains of mice that had been given a dose of ketamine. These neurons belong to networks that convey their signals by means of the neurotransmitter glutamate. Ketamine had been known since the 1990s to produce its effects by acting on such neurons – this in contrast to older antidepressants, which mainly affect neurons influenced by serotonin. But since ketamine’s effect persists long after it leaves the body, its action could not be explained by mere blockage of glutamate receptors on the surfaces of neurons. ...
To this end, the scientists focused on the ventral hippocampus ... After mapping out gene expression in cells from this area of the mouse brain, the researchers identified a subpopulation of neurons with a characteristic genetic signature. Ketamine had increased these neurons’ expression of a gene called Kcnq2, which encodes a potassium channel – ... In a series of elaborate experiments on the molecular and cellular levels, which included electrophysiological, pharmacological, behavioral and functional studies, the scientists confirmed their major finding: Ketamine exerts its lasting antidepressant effect by enhancing the Kcnq2 potassium channels in a certain subtype of glutamate-sensitive neurons. ..."
From the abstract:
"A single sub-anesthetic dose of ketamine produces a rapid and sustained antidepressant response, yet the molecular mechanisms responsible for this remain unclear. Here, we identified cell-type-specific transcriptional signatures associated with a sustained ketamine response in mice. Most interestingly, we identified the Kcnq2 gene as an important downstream regulator of ketamine action in glutamatergic neurons of the ventral hippocampus. We validated these findings through a series of complementary molecular, electrophysiological, cellular, pharmacological, behavioral, and functional experiments. We demonstrated that adjunctive treatment with retigabine, a KCNQ activator, augments ketamine’s antidepressant-like effects in mice. Intriguingly, these effects are ketamine specific, as they do not modulate a response to classical antidepressants, such as escitalopram. These findings significantly advance our understanding of the mechanisms underlying the sustained antidepressant effects of ketamine, with important clinical implications."
Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2 (no public access)
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