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  1. 5-HT2A
    The science behind many anti-depressant medications appears to be backwards, say the authors of a paper that challenges the prevailing ideas about the nature of depression and some of the world's most commonly prescribed medications.

    The authors of the paper, posted by the journal Neuroscience & Biobehavioral Reviews, combed existing research for evidence to support the theory that has dominated nearly 50 years of depression research: that depression is related to low levels of serotonin in the gaps between cells in the brain.

    The low-serotonin theory is the basis for commonly prescribed anti-depressant medications called selective serotonin re-uptake inhibitors, or SSRIs, which keep the neurotransmitter's levels high by blocking its re-absorption into the cells that release it.

    Those serotonin-boosting medications actually make it harder for patients to recover, especially in the short term, says lead author Paul Andrews, an assistant professor of Psychology, Neuroscience & Behaviour at McMaster.

    "It's time we rethink what we are doing," Andrews says. "We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery."

    When depressed patients on SSRI medication do show improvement, it appears that their brains are actually overcoming the effects of anti-depressant medications, rather than being assisted directly by them. Instead of helping, the medications appear to be interfering with the brain's own mechanisms of recovery.

    "We've seen that people report feeling worse, not better, for their first two weeks on anti-depressants," Andrews says. "This could explain why."

    It is currently impossible to measure exactly how the brain is releasing and using serotonin, the researchers write, because there is no safe way to measure it in a living human brain. Instead, scientists must rely on measuring evidence about levels of serotonin that the brain has already metabolized, and by extrapolating from studies using animals.

    The best available evidence appears to show that there is more serotonin being released and used during depressive episodes, not less, the authors say. The paper suggests that serotonin helps the brain adapt to depression by re-allocating its resources, giving more to conscious thought and less to areas such as growth, development, reproduction, immune function, and the stress response.

    Andrews, an evolutionary psychologist, has argued in previous research that anti-depressants leave patients in worse shape after they stop using them, and that most forms of depression, though painful, are natural and beneficial adaptations to stress.

    Paul W. Andrews, Aadil Bharwani, Kyuwon R. Lee, Molly Fox, J. Anderson Thomson. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience & Biobehavioral Reviews, 2015; 51: 164 DOI: 10.1016/j.neubiorev.2015.01.018

    February 17, 2015



  1. Rob Cypher
    That's weird, because SSRIs used to work well for me when I first used them. They made me feel like I was on a low dose DXM trip without the coordination issues. 15 years later though, they seem to have only a mild effect on me.
  2. LuLu81
    I really think antidepressants ate over prescribed.

    I tend to get depression regularly, however it is usually because of something specific in my life that has happened, rather than something that is constant.

    I have explained this to all my doctors but every one has prescribed me an antidepressant. I've been on Prozac, Citalopram, Amitriptyline, trazadone and now Sertraline and a couple of others who's names I cant remember and i have been on and off them since I was 16. I have found that its pretty pointless for me to take these medications as my situational depression happens regardless.

    The only antidepressant that I continue to take is Amitriptyline but that is only because of its off label use in helping with my peripheral neuropathy.
  3. Crystal_Queen
    This article isn't saying antidepressants don't work..
    But the way they work, as well as the understanding of depression is reversed.
    In this theory...

    Depression is caused by excess Serotonin.
    SSRI's overload the brain with even more Serotonin.
    The brain responds by turning down Serotonin Release. (acute tolerance)
    Eventually serotonin reserves "run out" with re-uptake being chronically blocked. (chronic tolerance)
    Total effect is a decrease in Serotonin.

    It makes perfect sense...
    It explains why they don't work right away, why you don't get high by taking more or absorbing it faster.
    Why they can be given long term, when all other drugs cause tolerance and escalating doses.

    Another way of looking at this...
    Think of Serotonin as an "emotion/empathy" enhancer instead of a "happiness" enhancer.
    Depressed people aren't deficient in happiness, they are excessive in emotions.
    SSRI's eventually turn down "emotional response"... so people are less likely to "care" about being hurt and react in an emotional way, like hurt themselves or suicide. This also explains why people claim to feel less depressed... but not happy.... they don't cry anymore... but they still don't laugh sort of thing.
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