Wednesday, November 20, 2013

Ketamine Findings Open New Doors to Antidepressant Research

Research suggesting that the anesthetic drug ketamine acts quickly to reduce depressive symptoms is now being supplemented by studies into other substances that operate on similar pathways, according to two reports in the current issue of Biological Psychiatry.

One study of depressed patients by scientists from Taiwan’s China Medical University and from UCLA found that sarcosine improved mood scores and reduced depressive symptoms, when compared with patients taking the antidepressant citalopram. Sarcosine’s effects, however, are the opposite of ketamine’s. Sarcosine enhances activity of the NMDA glutamate receptor, while ketamine blocks it. Further research is needed to clarify these paradoxical outcomes, said John Krystal, M.D., the journal’s editor.

The second study noted that prior research identified the mammalian target of rapamycin (mTOR) as a key mediator of the antidepressant effects of ketamine. Researchers led by Ronald Duman, Ph.D., a professor of psychiatry, neurobiology, and pharmacology at Yale University School of Medicine, found that scopolamine, a muscarinic acetylcholine receptor antagonist, caused rapid activation of mTOR signaling and increased the number of synaptic connections in the prefrontal cortex.

"These effects are similar to the actions of ketamine, showing that two drugs with completely different receptor blocking profiles have common downstream actions linked to rapid antidepressant responses," said Duman in a statement. "Moreover, the increase in synaptic connections reverses the deficit caused by stress and depression and thereby reinstates the normal control of mood and emotion."

To read more about recent research on ketamine, see the Psychiatric News article “Ketamine Shows Rapid Action In Treatment-Resistant Depression.” Also see the study
"Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial" in the American Journal of Psychiatry.
Image: Iculig/