A new study suggests that ketamine, an increasingly popular treatment for depression, has something in common with drugs such as fentanyl and oxycodone.
The small study found evidence of the effectiveness of ketamine in depression, which has been demonstrated in many small studies decade, comes from its interaction with the brain's opioid system. A team from Stanford University reported on Wednesday in The American Journal of Psychiatry .
"We think ketamine acts as an opioid," says Alan Schatzberg, one of the authors of the study and professor of psychiatry and behavioral science at Stanford. "That's why you get these fast effects."
So far, most researchers have attributed the success of ketamine to the brain's glutamate system, which is involved in learning and memory. In contrast, the opioid system controls pain, reward and addictive behavior.
Ketamine is an anesthetic that is often given to children in the emergency department. It is also a popular but illegal party drug that can lead to an out-of-body experience at high doses.
And in recent years, ketamine has been increasingly used as an off-label treatment that doctors prescribe for patients suffering from severe depression that does not respond to other drugs. Unlike traditional antidepressants like Prozac, which can take weeks to work, infusion or nasal administration of ketamine typically results in hours.
The findings of the new study suggest that taking ketamine for depression may lead to abuse or addiction, says Schatzberg, who has financial ties to several drug companies. Ketamine has a less potent effect on opioid receptors than drugs like fentanyl or oxycodone, he says, "but that does not mean it's safer."
Other researchers say the implications of the study are not so clear.
The results are pretty intriguing, "says Carlos Zarate, a researcher at the National Institute of Mental Health, who has been studying the effects of ketamine on depression for more than a decade." However, this study is preliminary and its results must be replicated. "
The new study is "interesting and exciting," says Ronald Duman, a professor of psychiatry and neurobiology at Yale, who has published research showing how ketamine brain causes cells to form new connections.
But Duman Unconscious that the effect of ketamine on the opioid system is key to its effectiveness in the treatment of depression, he notes that the effect of ketamine on the brain's glutamate system is very strong, while the drug "has a relatively low affinity for Opiate receptors. "
The Stanford team chose a study after studying glutamate ga b system alone are not very effective antidepressants, says Schatzberg. They also knew that opioid drugs had once been used to treat depression but were largely given up because of abuse concerns.
The team designed an experiment to treat patients with depression in two ways. The first was to give them an infusion of ketamine alone. The second was administering to each patient the drug naltrexone, which blocks the action of opioid drugs before they receive ketamine infusion.
An analysis of a dozen patients who received both treatments showed a dramatic difference. Seven out of 12 saw their symptoms of depression decreased by at least 50 percent the day after ketamine alone. But when they first received naltrexone, there was "virtually no effect," says Carolyn Rodriguez, one of the authors of the study and assistant professor of psychiatry and behavioral science at Stanford.
Rodriguez, who has introduced the use of ketamine as a pioneer to treat obsessive-compulsive disorder, says the study does not prove that the drug works primarily through the brain's opioid system. Instead, she calls the result "the beginning of a conversation" and says it "highlights that the mechanism of action of ketamine is complicated."
Rodriguez has worked as a consultant to several pharmaceutical companies, including Allergan, which develops a depression drug that works like ketamine in the brain.
One possibility is that the effect of ketamine on opioid receptors can provide immediate, but short-term relief from depression, says Rodriguez, while the effect of the drug on the glutamate system could be the cause of this relief week or more ,