‘Darwinian’ test uncovers an antidepressant’s hidden toxicity.

Rodent study finds that exposure to an antidepressant in womb or in youth can cause lifetime decline in sexual behavior, body weight, and competitive ability.

Once you strip away the scientific verbiage, it becomes obvious that the prolonged use of these drugs creates generations of "losers".

As reported on Science Daily

Because of undetected toxicity problems, about a third of prescription drugs approved in the U.S. are withdrawn from the market or require added warning labels limiting their use. An exceptionally sensitive toxicity test invented at the University of Utah could make it possible to uncover more of these dangerous side effects early in pharmaceutical development so that fewer patients are given unsafe drugs.

To prove the point, the U researchers ran their test on Paxil, an antidepressant that thousands of pregnant women used in the years before it was linked to an increased risk of birth defects. The U.S. Food and Drug Administration now requires a warning about use in the first trimester of pregnancy. In the U study, mice exposed during development experienced multiple problems: males weighed less, had fewer offspring, dominated fewer territories and died at a higher rate. Females took longer to produce their first litters, had fewer pups and pups that were underweight. The drug doses were relatively close to those prescribed for people. In the conventional animal safety testing reported by the drug's manufacturer, no reproductive side effects emerged until rodents took doses multiple times higher than those given to treat depression.

"We are seeing effects at a dose that is close to human levels. And we are doing it exactly the way we need to determine if it presents a risk of harm to a developing fetus," says University of Utah biologist Shannon M. Gaukler, the study's lead author who recently completed a doctoral degree at the U. The study will be published in the January-February issue of Neurotoxicology and Teratology, which has posted a preprint online.

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Testing Paxil

In the Paxil study, the researchers gave food laced with the antidepressant to 20 breeding pairs of mice for several weeks, until all had produced up to four litters. Doses were equivalent to about 1.8 times the level typically prescribed for people. The offspring also ate Paxil-laced chow until they reached breeding age. The researchers then released the exposed offspring into the competitive arena with the offspring of a control group of mice never exposed to Paxil. Groups consisted of eight males and 14 to 16 females, creating population densities comparable to those seen in the wild. The researchers started five such populations and kept them going for six months.

Males exposed to Paxil were about half as likely to control a territory. They also lagged behind control males in body weight throughout the weeks of competition and were more likely to die. Exposed males produced 44 percent fewer offspring. Exposed females showed no significant weight or mortality differences, but they produced half as many offspring as control females at the initial assessment. Their fecundity rebounded at later time points.