Faster Antidepressant Shows Promise
> 9/6/2007 12:33:59 PM

Approximately half of patients do not achieve remission from depression using only medication. Those who do get better must wait for several difficult weeks before they notice any positive results. That is why scientists have been looking for another type of antidepressant to augment or possibly even replace selective serotonin reuptake inhibitors. SSRIs work by preventing the brain from clearing away serotonin that has already been used, allowing excess neurotransmitters to build up and generate a signal multiple times. Dr. Guillaume Lucas has just tested a new drug that, while still focusing on serotonin, acts directly on receptors instead of slowly building up existing neurotransmitters.

The two serotonin receptor agonists, RS 67333 and prucalopride, that Dr. Lucas used to directly affect neurons have been helpful with other illnesses such as migraines, but this is the first time that they have been successfully tested on depression. Lucas observed a change in both the behavior and brain function of depressed laboratory mice given serotonin agonists.

Drugged mice spent less time than controls immobilized during a swimming test commonly used to measure depression. In addition, these mice maintained a healthier appetite during stress. Beyond behavior, there were measurable changes in the brain, like the growth of new neurons in the hippocampus, that serve as indicators of success for currently used antidepressants.

These behavioral and neural changes were even more pronounced than those observed in mice given the SSRI citalopram. They also occurred much faster; changes were noticeable after only three days instead of weeks. The enhanced speed and efficacy of agonists makes a strong case for their superiority to traditional SSRIs. However, we must keep in mind that this research is still in the earliest stages. Agonists may avoid the unwanted weight and libido changes brought on by SSRIs only to cause an entirely new set of problems. It will be a long time before the promise of these first results can be confirmed with human testing. In the meanwhile, scientists should certainly keep looking for more serotonin agonists that can cross the blood-brain barrier. If they do turn out to be as effective on humans as on mice, then psychiatrists will have valuable new tools for preventing suicide and restoring the quality of life.

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