The Hartford Courant
August 19, 2010
Yale researchers hope to develop a form of ketamine — an effective but very dangerous antidepressant — that's safe, easy to use and effective within hours of taking it.
A new study sheds light on how the drug affects operations in the brain, and why it works so fast compared to other antidepressants. The study was led by Ronald Duman, a professor of psychiatry and pharmacology at Yale, and George Aghajanian, professor of pharmacology. It will be published Friday in the journal Science.
The most popular antidepressants like Prozac and Zoloft, which are selective serotonin reuptake inhibitors (SSRI), can take weeks before patients feel their effects. Saying that it's "like a magic drug," Duman notes that one dose of ketamine works fast and can last for up to 10 days.
"Clearly, there is a need for a ketamine-like drug with rapid results," he said. Adding to its benefits is that studies indicate that about 70 percent of patients who are resistant to other antidepressants respond to ketamine.
Ketamine was developed in the early 1960s and used as an anaesthetic, commonly for soldiers in Vietnam. In the 1990s, it gained a reputation as a "party drug" (known as "Special K") and has been known to cause short-term psychotic symptoms.
For about 10 years, its potential as an antidepressant has been known. Because of its potency, though, it is only administered intraveneously in clinical settings, which significantly limits its use. It's usually prescribed in low doses for patients suffering severe depression who have been resistant to other treatments.
With new information about how it works, though, Duman believes a form of ketamine could be developed that's much safer and more convenient to take.
"That would be the ultimate goal, to develop the drug as a pill," he said.
Unlike SSRI medications, ketamine does not involve the chemical serotonin as a primary function. By testing ketamine on rats, the researchers were able to examine how the drug worked its way through the brain. What they found was that ketamine helped restore synaptic connections between the neurons, which had been damaged by chronic stress. It does this partly by activating an enzyme called mTOR, setting of a chain reaction.
"Ketamine is able to jumpstart and get these systems revved up again," Duman said.
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