Ketamine a Potential Therapeutic Agent for Depression

Ketamine may be an effective potential therapeutic agent for the treatment of depression, according to a recent scientific review of research published in the journal Science.

The review, co-authored by Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and Professor of Neurobiology, and George K. Aghajanian, professor of psychiatry at Yale, examined more than a decade of research on ketamine and its potential to become the first new antidepressant since the 1970s.

Evidence examined in the review suggests that ketamine, a N-methyl-D-aspartate receptor antagonist, aids in regenerating synaptic connections between brain cells that have been damaged by depression and stress.

Current antidepressant medications may take weeks or months to improve the symptoms of depression and are not effective in one out of every three patients. Ketamine works on a different type of neurotransmitter system than current medications. Understanding how ketamine functions in the brain may lead to the development of a new class of antidepressant that could provide relief to those suffering from chronic depression.

It is vital for researchers to understand how ketamine works in the brain because of the drug’s hallucinogenic effects. In large doses, the drug can cause short-term symptoms of psychosis. Development of the drug is hindered by fears of its potential for abuse.

In patients that are resistant to typical antidepressant medications, ketamine has been shown to produce antidepressant responses within hours. While the response to treatment is rapid, the improvement in symptoms only lasts for a week to 10 days and impairs the patient for hours after dosing. The drug is administered through infusion. An oral form is available but it is not optimally absorbed.

The findings presented in the review form the basis of a synaptogenic hypothesis of depression and treatment response, and highlight the importance of homeostatic control of mood circuit connections.