* Findings may lead to new, better treatments
* May help doctors identify those unlikely to get relief
By Julie Steenhuysen
CHICAGO, Jan 13 Antidepressants fail to help
about half of the people who take them, and a study in mice may
help explain why.
Most antidepressants -- including the commonly used Prozac
and Zoloft -- work by increasing the amount of serotonin, a
message-carrying brain chemical made deep in the middle of the
brain by cells known as raphe neurons.
Researchers at Columbia University Medical Center in New
York said on Wednesday that genetically engineered mice that
had too much of one type of serotonin receptor in this region
of the brain were less likely to respond to antidepressants.
"These receptors dampen the activity of these
(serotonin-producing) neurons. Too much of them dampen these
neurons too much," Rene Hen of Columbia, whose study appears in
the journal Neuron, said in a telephone interview.
"It puts too much brake on the system."
Hen said the finding may be useful in giving doctors an
idea of whether a patient will respond to an antidepressant.
And it could also help drugmakers populate better clinical
trials to help identify new drug compounds that work for people
who are unlikely to benefit from conventional antidepressants.
"The goal is to figure out something that is useful for the
non-responders," he said.
For the study, Hen and colleagues needed to reach serotonin
receptors in just the right part of the brain.
To do this, the team used mice that were genetically
altered to have fewer serotonin receptors only in the region
where the serotonin-producing raphe neurons are located.
Once the team had mice that had different levels of
serotonin receptors in different parts of the brain, they did a
behavior test that assesses boldness when mice get food in a
brightly lit area.
Mice on antidepressants usually become more daring, but the
drugs had no such effect on mice with surplus serotonin
"The most dramatic finding is that the mice that have high
levels of receptors in these serotonin neurons do not respond
to fluoxetine or Prozac," Hen said.
But when they reduced the number of these receptors -- or
molecular doorways -- they were able to reverse the effect, he
"By simply tweaking the number of receptors down, we were
able to transform a non-responder into a responder," Hen
At least 27 million take antidepressants in the United
States, nearly double the number that did in the mid-1990s.
Eli Lilly and Co's (LLY.N) Prozac, known generically as
fluoxetine, and Pfizer Inc's (PFE.N) Zoloft or sertraline
belong to a class of antidepressants known as selective
serotonin reuptake inhibitors, or SSRIs. Other common
antidepressants include Forest Laboratories Inc's FRX.N
Celexa, or citalopram, and Lexapro, or escitalopram; and
GlaxoSmithKline's (GSK.L) Paxil or paroxetine.
(Editing by Mohammad Zargham)