Ketamine And Depression

Custom image representing Ronald Duman's studies with neuron formation in rats, with base images retrieved from Juvenile Bipolar Research Foundation.

"Traditional antidepressants like Prozac work on a group of chemical messengers in the brain called the serotonin system. Researchers once thought that a lack of serotonin was the cause of depression, and that these drugs worked simply by boosting serotonin levels.
Recent research suggests a more complicated explanation. Serotonin drugs work by stimulating the birth of new neurons, which eventually form new connections in the brain. But creating new neurons takes time — a few weeks, at least — which is thought to explain the delay in responding to antidepressant medications.
Ketamine, in contrast, activates a different chemical system in the brain — the glutamate system. Researcher Ron Duman at Yale thinks ketamine rapidly increases the communication among existing neurons by creating new connections. This is a quicker process than waiting for new neurons to form and accomplishes the same goal of enhancing brain circuit activity.
To study how ketamine might work, Duman turned to rats. The first image below shows the neuron of a rat that has received no ketamine treatment. The small bumps and spots on the side of the neuron are budding connections between neurons.
Just hours after giving the rats doses of ketamine, Duman saw a dramatic increase in the number of new connections between brain cells. This increase in neuronal connectivity is thought to relieve depression."

- text from How Ketamine Works to Treat Depression by Andrew Prince (June 5, 2012)


"Ketamine has been used for decades as an anesthetic. It also has become awildly popular but illegal club drug known as "Special K."
Mental health researchers got interested in ketamine because of reports that it could make depression vanish almost instantly.
In contrast, drugs like Prozac take weeks or even months. And the frustrating thing is that depression medications really haven't changed much since Prozac arrived in the 1970s, says Sanjay Mathew from Baylor College of Medicine, who is in charge of the ketamine study at Ben Taub.
"Everything since then has been essentially incremental," he says. "There have been tweaks of existing molecules."
But ketamine represents much more than a tweak, Mathews says."It's a completely different mechanism," he says. "And the focus is on really rapidly helping someone get out of a depressive episode."
...I talk to Carlos Zarate, who does ketamine research at the NIH and has never met Merrill. Zarate says patients typically say, " 'I feel that something's lifted or feel that I've never been depressed in my life. I feel I can work. I feel I can contribute to society.' And it was a different experience from feeling high. This was feeling that something has been removed."I compare this to what Merrill said about her experience: "No more fogginess. No more heaviness. I feel like I'm a clean slate right now. I want to go home and see friends or, you know, go to the grocery store and cook the family dinner."
The similarities are hard to ignore.
And researchers say the consistent patient reactions have actually made it more difficult to do good studies of ketamine. The drug's effects are so powerful and distinctive, they say, it's hard to prevent doctors and patients in an experiment from figuring out who got the drug and who didn't."

- from Could A Club Drug Offer 'Almost Immediate' Relief from Depression?' by Jon Hamilton for NPR (Jan. 30, 2012)


"Carlos Zarate, a brain researcher at the National Institute of Mental Health who is studying ketamine, told NPR that depression is like a leaky faucet in the brain.
There are different ways to stop the leak, he says. “You can go straight to the faucet and you can fix it,” he says. “Or you can go to the water plant and shut down the water plant. The end result will be the same.”
The current antidepressants act in a way that is like shutting down the water plant, Zarate says. It takes a long time for the water to stop flowing through the miles of pipes that eventually lead to the leaky faucet.
He thinks the reason is that these drugs act primarily on the brain chemicals serotonin, norepinephrine and dopamine. Ketamine acts on a chemical called glutamate, which is much closer to the problem, Zarate says.
That’s nice, but ketamine can come with side effects that make antidepressants look like aspirin. These include urinary tract problems, hypertension, nausea, nightmares, memory problems and hallucinations. Zarate said because of troubling side effects, ketamine is unlikely to become a common depression treatment in and of itself. But understanding how ketamine works at treating depression could allow scientists to develop safer drugs that work in the same way."

- from Ketamine Nation? Special K Works Better Than Prozac At Treating Depression by Elizabeth Nolan Brown (Jan. 31, 2012)

Ketamine, rats, depression, neurons
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