Chemical imbalance. Newborn mice treated with Prozac showed reduced exploratory behavior in an elevated maze test.

Prozac Paradox

The drug fluoxetine--commonly known as Prozac--has been used as an antidepressant for almost 20 years, but a new study suggests that it may actually raise anxiety levels in newborn mice.

Fluoxetine is the oldest of the selective serotonin reuptake inhibitors (SSRIs) and the only one approved for pediatric use. The drug works by blocking the serotonin transporter (5-HTT), enabling this neurotransmitter to linger in the synapses and thus making it more available to uptake by target receptors. But this month, amid growing concern that SSRIs could cause suicidal behavior in children, the U.S. Food and Drug Administration ordered drugmakers to put strong new labels on all serotonin-based antidepressants.

Studies have already shown that disabling the serotonin transporter gene causes animals to display behaviors associated with depression and anxiety. Researchers at Columbia University, led by psychobiologist Mark Ansorge, sought to determine whether fluoxetine would have the same effect as knocking out the two copies of the transporter gene. They bred sets of mice with one, two, or no functioning copies of the 5-HTT gene. Then they randomly gave either saline injections or fluoxetine--at doses equivalent to therapeutic ones for humans--to newborn mice between 4 and 21 days old in each group. Nine weeks after the last injection, mice were given tests that revealed their emotional states.The drug had no effect on the mice lacking any 5-HTT; they already exhibited anxiety. But fluoxetine increased signs of anxiety in the other mice, the researchers announced today at the Society for Neuroscience's annual meeting in San Diego and report in the 29 October issue of Science. In comparison to the saline-treated pups, the fluoxetine-treated mice explored less while in a maze. They also took longer to start eating when placed in a novel setting and were slower to try to escape a part of the cage that mildly shocked their paws. All these behaviors are regarded as signs of anxiety and depression in animals.The authors say the period of brain development studied in the mice corresponds roughly to the last trimester of pregnancy through age 8 in humans. So, they conclude, "the use of SSRI medications in pregnant mothers and young children may pose unsuspected risks of emotional disorders later in life."The study "suggests that fluoxetine and probably other SSRIs may have additional unexpected problems," says Miklos Toth, a pharmacology professor at Cornell University's Weill Medical College in New York City. Some scientists caution, however, that the mice in this study were at a much younger developmental age than children likely to be treated for depression.Related sites
FDA Web site on SSRIs
Article on SSRI use in children