Sometime street drug hailed as antidepressant

COURTESY OF YALE UNIVERSITY Enlarge Image

Slides show the regeneration of synaptic connections that occur on ketamine.

A new antidepressant being tested in Canada appears to do what no other drug can -- increase connections between brain cells within hours to swiftly improve symptoms.

The finding by Yale University researchers may explain how one dose of ketamine can reduce symptoms of depression within 40 minutes among the hardest-to-treat cases, and could help spur development of quick-acting antidepressants.

About 17 per cent of the Canadian population will experience major depression at some point in their lives.

Prozac-like drugs and other antidepressants take at least two weeks to produce an effect, and sometimes months for a full effect. Even then, they work well in only about a third of patients.

The risk of suicide increases during those dangerous weeks or months of lag time.

"They start taking the drug, they're still depressed, they start to get a bit more energy, but their mood doesn't increase," said Dr. James Kennedy, director of the neuroscience research department at the Centre for Addiction and Mental Health in Toronto. "The problem is keeping the patient on the medication and preventing them from using their new energy in a bad way to kill themselves.

"This finding might help to prevent what has been a major clinical problem."

Ketamine is a fast-acting liquid anesthetic used mainly by veterinarians; it's also used in human medicine, even in children, because it doesn't depress breathing.

It's also an illegal club drug, known as "special K" or "vitamin K."

The street version is usually sold in a powder form that can be snorted or mixed into drinks, or dissolved into a liquid and injected.

It acts like LSD, causing vivid hallucinations in users and a sensation of floating outside their bodies.

Earlier studies involving patients with "treatment-resistant" depression have found that those given a single dose of ketamine experience rapid and significant improvement in symptoms. In a small study published earlier this month on patients with bipolar depression, 71 per cent of participants responded to ketamine versus six per cent who responded to a placebo.

"It's like a magic drug -- one dose can work rapidly and last for seven to 10 days," Ronald Duman, professor of psychiatry and neurobiology at Yale, said in a media statement.

"If someone is extremely ill, and in many cases may be even suicidal, having a drug that works rapidly like this is just a tremendous resource to have," Duman said in an interview with Postmedia News.

In experiments on rats, Duman's team found that ketamine acts on a pathway in the brain that forms new synaptic connections between neurons. Synapses are like phone lines that allow neurons to talk to one another. The drug increased synaptic connections as quickly as two to four hours after treatment.

"The number of spines where the synapses occurs is increased by ketamine in a very short time frame," Duman said.

"It's a pretty amazing effect when you think about it, that ketamine is able to produce this rapid increase in connectivity in the brain."

The drug also repaired connections between neurons damaged by chronic stress. Studies have shown that neurons can atrophy, or shrink, in response to chronic stress. Duman said ketamine may be able to reverse the effects of stress on the brain.

The goal now is to identify ketamine-like drugs that can have the same effect on the brain that can be administered more easily and don't have the potential for abuse. The Yale team is now testing several compounds.

However, "ketamine could be, and probably will be used until something better is available," said Duman, whose team's work is published this week in the journal Science.

-- Postmedia News

Republished from the Winnipeg Free Press print edition August 20, 2010 A23