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Ketamine appears to help regenerate synaptic connections between brain cells damaged by stress and depression, according to a review of scientific research published in the October 5 issue of the journal Science.

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

The anesthetic works on an entirely different type of neurotransmitter system than current antidepressants, which can take months to improve symptoms of depression and don’t 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.

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

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

The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health.

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

Source: Yale University