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Experimental Antidepressants Offer Faster Relief

But initial research involved only rats; clinical trials involving people are next step

WEDNESDAY, Sept. 5 (HealthDay News) -- A new class of antidepressants dramatically cut the time needed to take effect when they were tested on rats, a study found.

The study authors, from McGill University in Montreal, Canada, said they hope the finding will spur research into the family of drugs, raising the prospect of faster-acting antidepressants.

But, as always with studies involving animals, the findings must first be confirmed in humans.

"The only way we'll know is when a clinical trial is done" involving humans, said Gerald Frye, Joseph H. Shelton professor of neuropharmacology and neurotoxicology at the Texas A&M Health Science Center College of Medicine's department of neuroscience and experimental therapeutics. "It looks promising from an animal standpoint, and the animal systems they're using are pretty good, but this can only predict. There's no guarantee."

Frye was not involved with the study, which is published in the Sept. 6 issue of the journal Neuron.

Antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Celexa, are widely prescribed but can take up to six weeks to take effect, and they don't work for everyone. Many patients have to try several different drugs before achieving success, and only about 65 percent of people end up responding to a drug, according to an accompanying editorial in the journal.

That time lag can be critical for someone suffering from depression. "During that time, there is a risk of suicide," Frye said. "Anything you can do to get a faster response" is desirable, he added.

SSRIs work by enhancing the action of the neurotransmitter serotonin in the brain.

The new study looked at a new class of drugs known as serotonin4 (5-HT4) receptor agonists, which have a more specific effect.

"SSRIs interfere with the serotonin system and increase naturally transmitted serotonin to help the system readjust itself," Frye explained. "The new drugs act only on one receptor. They're more selective."

For the study, the researchers tested two serotonin receptor agonist compounds, called RS 67333 and prucalopride, in rats, comparing the drugs against the action of Celexa. Using different measures of depression, the researchers found that the two new drugs acted four to seven times faster and also seemed more powerful.

In one test, the researchers found that one of the serotonin receptor agonists took effect after only three days and completely erased the depressive symptoms after one week.

For instance, mild stress has been shown to reduce consumption of sugar water by rodents -- a behavior alleviated by weeks of SSRI treatment. But the McGill researchers found that one of the serotonin receptor agonists produced effects within three days and seemed to removed the depressive symptoms within a week.

The new drugs, however, may have side effects. "There are potential side effects, and that's where the rub could be with clinical trials," Frye said.

More information

For more on depression, visit the U.S. National Institute of Mental Health.

SOURCES: Gerald Frye, Ph.D., Joseph H. Shelton Professor of Neuropharmacology and Neurotoxicology, Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine; Sept. 6, 2007, Neuron

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