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Study in mice shows why antidepressants often fail

By chillinwill, Jan 15, 2010 | | |
  1. chillinwill
    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 receptors.

    "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 said.

    "By simply tweaking the number of receptors down, we were able to transform a non-responder into a responder," Hen said.

    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 Prozac, known generically as fluoxetine, and Pfizer Inc's 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 Celexa, or citalopram, and Lexapro, or escitalopram; and GlaxoSmithKline's Paxil or paroxetine

    Julie Steenhuysen
    January 13, 2010


  1. Canmedaa
    I think part of the issue with Anti-Depressants is really that the Drug companies and health authorities have grossly simplified the public's concept of brain chemistry and neurotransmitters. We've all seen the little cartoons and simulations of a synapse and the little particles in between and we all know what Serotonin is and maybe some of the other celebrity Neurotransmitters like Dopamine and Norepinephrine, but in reality the list of Neurotransmitters is intimidatingly long.

    The one's we hear about the most in the news are the monoamine's, which shouldn't be surprising since the earliest Anti-depressants were MAOI's: Monoamine Oxidase Inhibitors. Modern reuptake-inhibitors work on the same neurotransmitters as the old ones, just in a different way.

    There are variety of transmitter and modulator types that effect one's overall brain chemistry: Amino Acids, Monoamines, Gastrins, Neurohypophyseals, Neuropeptides, Opiods, Secretins, Somatostatins, Tachykinins, Gases, and Lord knows what else. Whose to say that depression is just Monoamines alone?

    I've said it before, and I'll say it again. Anti-Depressants are designed to correct chemical imbalances, pathologies. Being in a bad mood is, yes, hypothetically a change in the balance of your hormones, but it is not a pathological imbalance. Having low blood sugar one day because you havn't eaten does not mean you have diabetes, and it certainly doesn't mean you should start insulin therapy, and if you did...you'd likely have some poor results.

    Legitimate depression is like having low blood sugar without diabetes. Giving legitimately depressed people SSRI's is like treating them for diabetes,which they don't have.

    It's not that Anti-Depressants DON'T WORK, its that they don't work on people who don't need them. We tend to use Anti-Depressants like aspirin for the blues, but that just isn't how they should be used, nor is it how they are indicated for use in pharmacological therapy.

    Now this is just a wild, pull-out-of-my-ass statistical guess, but I would reackon confidently that less than 1 third of the people currently be treated with SSRI's actually have inherent chemical imbalances and therefore actually are indicated for use of the drug. Everyone else...I think it's being used like aspirin.

    This post was likely sloppy. I'm half awake. But suffice to say, Don't blame the drugs! Blame the fools giving them to people who don't benefit from them! SSRI's are very cool technology, they just have a bad rap from being grossly over-used.

    I think the non-responders in this article are the people who are legitimately depressed, in which case they need therapy and life changes, not the next method of messing around with monoamines.

    Thats my two-cents at eight-thirty in the morning!
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