Researchers have struggled to explain how the drug ketamine provides immediate relief to many chronically depressed and treatment-resistant patients.
In fact, scientists have been trying to explain the observation first made at Yale University for well over a decade.
New research now suggests that ketamine, normally used as a pediatric anesthetic, helps to regenerate synaptic connections between brain cells damaged by stress and depression.
The study, by Yale School of Medicine researchers, is published in the journal Science.
Most antidepressants can take weeks to lessen symptoms of depression and do not work at all for one out of every three patients.
Researchers have long sought to improve their understanding of ketamine as the drug works on an entirely different type of neurotransmitter system than current antidepressants.
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,” said Ronald Duman, M.D., professor of psychiatry and neurobiology.
Duman and George K. Aghajanian, M.D., also professor of psychiatry at Yale, are co-authors of the review.
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.
Unfortunately, in large doses, ketamine can cause short-term symptoms of psychosis, and is abused as the party drug “Special K.”
In their research, Duman and others show that in a series of steps ketamine triggers the release of the 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.
Researchers say attempts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. As such, investigators continue to study alternatives they hope can duplicate the efficacy and rapid response of ketamine.
Source: Yale University