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Study Roundup: Could ‘Special K’ Be the Next Treatment for Depression?

By synthesizing past reports and observing ketamine treatments in rodents, researchers at Yale find evidence that ketamine may be fit for more than just the club.

--by Nina Lincoff

The Gist

Of all patients suffering from depression and undergoing treatment, only one in three respond to the first antidepressant they try. Most go through months of trial with a second, third, or even fourth type of drug. For the clinically depressed, the ineffectiveness of initial treatments can be devastating. But researchers at Yale and the National Institute of Mental Health may have uncovered evidence of the efficacy of a fast-acting drug already on the market.

Ketamine, known in party circles as ‘Special K,’ has shown remarkable effectiveness in treating depressed patients who are immune to typical antidepressant treatment. Chronic depression correlates with a reduction in activity in brain regions that regulate mood and cognition, according to the report, published this week in the journal Science. Oftentimes in depressed patients, the neuronal synapses in certain areas of the brain misfire or are otherwise defective. Typical antidepressants can block or reverse these symptoms, though the response time varies.

Ketamine kicks in within hours, and one dose can last for 7-10 days. It seems that ketamine repairs connectivity within the brain, particularly in the prefrontal cortex and hippocampus, which regulate mood and cognition. Because of its notoriety as a party drug, however, FDA approved ketamine-based or even ketamine-like treatments may be a few years away.

The Expert Take

Today, most prescribed antidepressants are selective serotonin re-uptake inhibitors (SSRIs), which were developed more than 50 years ago.  These can take months to work, must be taken regularly, and are only effective for one out of three patients on the first try.

There are many people who are extremely ill and are in need of a novel, unique treatment like ketamine,” says Dr. Ron Duman, PhD, and co-author of the report. “The field really needs to move forward with developing drugs and further exploration of ketamine use for people who are in dire need.”

Patients who received a dose of ketamine reported to clinicians that they felt relief from depressive symptoms in a way they hadn’t before, said Duman. Some of these patients were previously unresponsive to conventional antidepressants.

“The most surprising to us,” says Duman, “and what is most shocking about the study, is the change within hours to the connectivity in neurons. We knew that typical antidepressants can affect neurochemical activity, but ketamine can actually improve the connections between neurons in the brain.”

The Bottom Line

Ketamine produces such a rapid and dramatic effect on synaptic function that results are practically immediate when compared with those of other treatments. Conventional antidepressants act by blocking the re-uptake of the monoamines serotonin and norepinephrine. Ketamine functions on glutamate receptors, which are synaptic receptors located primarily on neuronal membranes. Most things in the brain, says Duman, are mediated by glutamate.

“That’s...why it’s acting so rapidly,” says Duman. “The glutamate system is a much more important mediator of brain function than monoamines, which are much more modulatory.” In addition, ketamine improves the poor synaptic function and spinal density found in depressed patients. This strengthening rapidly induces synaptogenesis, or the firing of synapses in the brain.

Unfortunately, because of the social perception of the drug and the precedent for abuse, the FDA has not embraced ketamine-based treatments. For now, these findings can help refocus depression research on synaptogenesis and glutamate-based treatments.

Source and Method

Researchers compared studies that examined changes in brain function that occur during depression or chronic stress. They then compared the effects of typical antidepressants with those of ketamine treatment. When they observed rodents suffering from symptoms that mimic stress-based depression, they found that a single dose of ketamine could drastically reverse the physical deficiencies caused by chronic depression.

Not only does ketamine work more quickly, it also improves spinal density. SSRIs can potentially influence synaptic plasticity by effecting neurochemical function. Ketamine however, “rapidly increases the number and function of synaptic connections,” says Duman.

Other Research

In a previous issue of Science, researchers studied the glutamate system—the same one acted on by ketamine— as a pathway for faster-acting antidepressants. In 2007, the anti-depressant effects of ketamine were reported online in Biological Psychiatry.

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Tags: Drugs , Latest Studies & Research

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