‘Darwinian’ test uncovers an antidepressant’s hidden toxicity

Jan 1, 2015

By University of Utah

Because of undetected toxicity problems, about a third of prescription drugs approved in the U.S. are withdrawn from the market or require added warning labels limiting their use.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.

University of Utah biology professor Wayne K. Potts, the study’s senior author, says that detecting toxicity problems early in preclinical testing would not only protect patients from exposure to unsafe drugs, but also help pharmaceutical companies avoid wasting billions of dollars bringing drugs to market only to have them fail.

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7 comments on “‘Darwinian’ test uncovers an antidepressant’s hidden toxicity

  • The fed the mice 1.6 times the dose of Paxil a human would get. I wonder if the supposed toxicity was just the desired effect of the drug. It makes people relax, stop competing so strenously. It makes mice stop competing for territory.

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  • Read it again… the problems were documented at the same level as what would be prescribed for depression. It is the drug company who reported that birth defects occurred “only” after doses that were “multiple” times the typically prescribed levels. This study demonstrates problems as the typically prescribed levels. Reducing levels of assertiveness is not the problem. Early death, birth defects, and low birth weight are, obviously, serious.

    It is somewhat abusing that this study is reported out of the University of Utah (excellent university) even though Utah is the most conservative state that openly discourages the teaching of evolution and has a state legislature that is dominated by Tea Party Mormon Republicans!

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  • 3
    Michael says:

    Mice are very intelligent and lively. Over the years it has been my privilege to raise a lot of mice and at no time have any of them exhibited any signs of depression. My question is whether the University of Utah researchers have considered whether there are any special conditions in the environment that would make it necessary to prescribe antidepressants for them. I assume they volunteered for the tests but even so it is sad to read of 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. Presumably these side effects may cause depressed mice in Utah to think again about seeking medication for this condition.

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  • One of the problems of treating depression, whether pharmaceutical or otherwise, is that depression, in at least some cases, may not be any kind of malfunction. Instead it may be a more or less inevitable consequence of circumstances and justifiable loss of hope. Might be better to treat the circumstances rather than trying to disrupt the otherwise normal physiological response to those circumstances. Vary the circumstances and vary the consequential depression.

    Same applies to things like obesity. Obesity may be a normal physiological response to defend body tissues against various onslaughts. So investigating drugs that disrupt the obesity response will exacerbate the original problem by causing the real damage to remain relatively unmitigated.

    Maybe a better drug would not suppress but instead augment the depression response. Enough to stimulate attempts to do something productive to change the situation. Possibly ice or crystal meth might be what they really need.

    From my limited experience the people who I’ve met that occasionally toy with ice on the weekends tend to be electrical apprentices whose very low pay, lack of social status, and lack of effective training continually exposes them to a high probability of accidental death and other depressing influences. Their only saving grace is that they have an actual job and income and therefore are considered insubstantially ‘mateworthy’ by the opposite sex, in a Darwinian sense. After getting into unprovoked fights for mating opportunities in bars etc they then may become subject to external intervention and might even have their lives prolonged sufficiently to reach maturity and to enable eventual reproduction.

    Unfortunately they will have already lost the fight for territory and suitable nesting sites. (Owing to the influx of the extremely well-funded and subsidised rival offspring of the prevailing officials of the Chinese Communist Party).

    At some point it can only end in tears. Hence the hoplesseness. The mice seem to have it relatively easy. Makes one wonder which species is experimenting on the other.

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  • 7
    sirald66 says:

    {sigh} Once again we have to do the new reporters job.

    News title fail, as usual.

    But if you go to the University of Utah press release where they stole the title from, it explains the reference.

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