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Researchers Discover How Ketamine Defeats Chronic Depression

Anesthetic drug provides immediate relief but can be dangerous in large doses (Oct. 5)

Many chronically depressed and treatment-resistant patients experience immediate relief from symptoms after taking small amounts of the anesthetic drug ketamine. For a decade, scientists have been trying to explain the observation, first made at Yale University.

Now, evidence suggests that ketamine helps regenerate synaptic connections between brain cells damaged by stress and depression, according to a study by Yale researchers published in the October 5 issue of Science.

Ketamine works on a different type of neurotransmitter system than current antidepressants, which can take months to improve symptoms of depression and do not work at all for one out of every three patients. Understanding how ketamine works in the brain could lead to the development of an entirely new class of antidepressants, offering relief for tens of millions of people suffering from chronic depression, according to the researchers.

“The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century,” said Dr. Ronald Duman, a professor of psychiatry at Yale.

Understanding how ketamine works is crucial because of the drug’s limitations. The improvement in symptoms, which are evident just hours after ketamine is administered, lasts only a week to 10 days. In large doses, ketamine can cause short-term symptoms of psychosis and is abused as the party drug “Special K.”

In their study, Duman and colleagues show that ketamine triggers the release of the neurotransmitter glutamate, which in turn stimulates the growth of synapses. Research at Yale has shown that damage to these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine.

Efforts to develop drugs that replicate the effects of ketamine have produced some promising compounds, but they do not act as quickly as ketamine. Researchers are investigating alternative therapies that they hope can duplicate the efficacy and rapid response of ketamine in depressed patients.

For more information, visit the Yale University Web site.

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