Baby Mice on Antidepressants Grow Up Depressed

Study finds they also develop anxiety when given generic Prozac

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HealthDay Reporter

TUESDAY, Oct. 26, 2004 (HealthDayNews) -- Mice who were given the generic equivalent of Prozac soon after they were born were prone to anxiety and depression as adults, new research concludes.

Even though the study was not done in humans, it does raise questions about the safety of antidepressants in pregnant women and in young children.

"It seems a reasonable conclusion that these medications are probably acting differently in an underdeveloped nervous system than in a developed nervous system," said Dr. Jay Gingrich, senior author of the study, which appears in the Oct. 29 issue of Science. Gingrich presented the results Tuesday at the Society for Neuroscience meeting in San Diego.

The findings come less than two weeks after the U.S. Food and Drug Administration mandated stronger "black box" warnings -- the government's strongest safety alert -- for all antidepressants. That move was largely an outcome of a continuing controversy over the use of antidepressants in children and teens.

Last year, British authorities declared that no antidepressants except Prozac should be used in children or adolescents. Earlier this year, the FDA asked drug manufacturers to change the labeling of 10 drugs to reflect the need to monitor young patients more closely. And in August, the FDA released information on an analysis by a senior FDA epidemiologist finding that, overall, children using antidepressants were 1.8 times more likely to have suicidal tendencies than depressed children taking placebos.

Prozac (generic name fluoxetine) is the only medication approved to treat depression in children and adolescents. Other drugs are used, however, based on evidence of their effectiveness from clinical trials.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and works by blocking a serotonin transporter, thereby making serotonin more easily available to receptors that need it. Serotonin is a neurotransmitter that controls a number of functions, including mood, appetite and energy levels.

The researchers had previously shown that genetically altered mice with the transporter knocked out actually grew up to exhibit more depression and anxiety. This was contrary to what the scientists had predicted. "We thought they would act like they were on chronic doses of SSRIs," Gingrich said.

Not long after, researchers in New Zealand found that humans with a genetic variant that altered the level of expression of this transporter ended up with anxiety and depression as adults if they were exposed to lots of stress, such as a divorce or job loss.

The current researchers have essentially found the same thing in mice.

They treated baby mice from the fourth to the 21st day of life with fluoxetine, let them group up "normally," then tested them when they reached adulthood. "The mice manifested almost precisely the same behavior as the genetically altered mice. There was more depression and anxiety related behavior," Gingrich said.

It seems that if the disruption of the serotonin transporter, even a temporary disruption, could affect later brain development.

The period of brain development studied in the mice corresponded roughly to the last trimester of pregnancy through 8 years of age in a human. "We don't know if longer or shorter periods would produce the same thing," Gingrich said.

Other experts have cautioned that children this young would probably not be prescribed an antidepressant.

There is still the issue of an expecting mother taking an SSRI, however. "The percentage of women and children being exposed to medications seems to be increasing, and it does make me concerned," Gingrich said. "These results are in mice. We don't know if they are applicable to humans but, if they are, it could actually be quite serious. We're talking about unforeseen long-term effects that might increase the risk to already somewhat higher risk people."

Still Gingrich's advice to pregnant women is the same: Antidepressant drugs should be considered only after other options have been tried. "Once those have been exhausted, then you run into a situation where you just have to make the best decision," he said. "There's not going to be an easy decision. What this does is add maybe one more finding in the negative ledger that people have to think about in the risk and reward ratio. It's still a hypothetical risk, but I think it's a risk nonetheless."

More information

The U.S. Food and Drug Administration has more on antidepressant use in children, teens, and adults.

SOURCES: Jay A. Gingrich, M.D., Ph.D., assistant professor of clinical psychiatry, Columbia University and New York State Psychiatric Institute, New York; Oct. 29, 2004 Science

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