Content area
Full Text
Researchers identify a pathway associated with a faster onset of antidepressant effects
A revolutionary breakthrough in the treatment of depression occurred in the late 1950s with the discovery of the monoamine oxidase inhibitors and tricyclic antidepressants. Since then, newer agents, starting with Prozac, were introduced. These newer antidepressants had fewer side effects and thus were easier to prescribe and manage in patients.
But there has always been one concern about antidepressant medications: Even when effective, they have a slow onset of action. Typically, they take nine to 14 days to have any impact, and perhaps weeks to deliver their full effects, even as patients continue to endure painful symptoms, diminished functioning, and an increased suicide risk. But what if an antidepressant could offer a more rapid onset, with sustained antidepressant effects?
Looking for a faster onset of action
Research initiated at Yale University and later extended to the National Institute of Mental Health (NIMH) has explored the use of ketamine to help understand and address the delayed-onset action of currently available antidepressants.
Ketamine, which has been employed as a human and animal anesthetic, has been found to act in the human brain by blocking the N-methyl-D-aspartic acid (NMDA) receptor, which receives nerve signals carried by the neurotransmitter glutamate. Studies have suggested that dysregulation in glutamate activity could be a causative factor in depression.
Ten years ago, investigators at Yale reported antidepressant effects of a single dose of intravenous (IV) ketamine in seven depressed patients.1 Dr. John Krystal, who chairs the Department of Psychiatry at Yale University School of Medicine, has been studying ketamine since 1989 and was the senior author of that study. He found the antidepressant effect of ketamine extraordinary.
"It is simply striking to see someone who has struggled with long-standing treatmentresistant symptoms of depression get better overnight. It is a remarkable thing to see," Krystal says.
Six years following that Yale report, investigators at the NIMH replicated...