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Mental Health
The serotonin theory of depression: a systematic umbrella review of the evidence (20 July 2022)
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<blockquote data-quote="tareload" data-source="post: 234058"><p>[URL unfurl="true"]https://www.newsweek.com/2022/09/30/antidepressants-work-better-sugar-pills-only-15-percent-time-1744656.html[/URL]</p><p></p><p><em>Instead, she argues, the drugs change "normal brain states" and "normal mental states and processes" in ways not that much different than recreational drugs like alcohol. They obscure psychotic symptoms by "superimposing" an abnormal drug state over other effects. In SSRIs, the small advantages seen in placebo-controlled trials, she suggests, can be attributed to emotional numbing that reduces the intensity of feelings causing the depression and anxiety, at the expense of a fuller experience of the ups and downs of life. The crippling sadness that sometimes follows a reduction in SSRI medication is caused by the chemical dependence the drugs can cause in the brain and withdrawal effects.</em></p><p><em></em></p><p><em>....</em></p><p><em></em></p><p><em>Stress hormones cause the brain to be flooded with the neurotransmitter glutamate, placing it in a state of chronic overstimulation, says Dr. Michael Thase, a professor of psychiatry at UPenn's Perelman School of Medicine. "Glutamate is elevated when you are distressed and aroused—it's also elevated briefly when we're really enthusiastic and up about stuff," he says. "But the kind of elevation of glutamate that's associated with prolonged intractable, severe distress becomes neurotoxic."</em></p><p><em></em></p><p><em>Over time, brain imaging suggests, this overactivation can cause neurons to shrink and become less connected to one another. Tiny proteins, which support dynamic growth and a healthy brain, dry up in the neurons of the hippocampus, the memory center of the brain, and the prefrontal cortex, where executive functions reside. The spiny arms that form the connections between neurons, known as dendrites and axons, shrivel up. This toxic environment seems to cause a dysregulation of the brain systems needed to perform routine actions. A lack of sleep and an inability to function in daily life creates more stress, releasing more glutamate. The patient spirals downwards.</em></p><p></p><p></p><h3><strong>No Better Than a Sugar Pill</strong></h3><p>A few weeks after the Horowitz paper came out, a team of researchers at the U.S. Food and Drug Administration, along with Kirsch, a long-time critic of the drugs from Harvard Medical School, published the most comprehensive analysis to date of all the antidepressant clinical trial data in its files, much of it previously unpublished. The study, which examined 232 placebo-controlled trials of 73,388 patients diagnosed with major depressive disorder, suggested that the active ingredients in 10 of the most popularly prescribed antidepressant medications made a meaningful difference in only 15 percent of the patients who took them, almost always in those patients suffering from the most severe depression.</p><p></p><p></p><p>The study, along with others, adds to mounting evidence suggesting that the active ingredients of SSRIs can make the biggest difference in patients who have severe depression, and often are of only marginal utility to those suffering from mild to moderate depression. Why, then, are they so overprescribed?</p><p></p><p>One reason may be that SSRIs are effective for many people not because the drug itself is working but because of the placebo effect. The simple act of treating a patient creates an expectation of healing that results in an improvement in the patient's condition. Previous research has generally found that the placebo effect is successful in 30 to 40 percent of cases of depression—in other words, a third of those who receive a pill or a shot that has no active ingredient get better from the simple fact that they are receiving care and attention from another human being.</p></blockquote><p></p>
[QUOTE="tareload, post: 234058"] [URL unfurl="true"]https://www.newsweek.com/2022/09/30/antidepressants-work-better-sugar-pills-only-15-percent-time-1744656.html[/URL] [I]Instead, she argues, the drugs change "normal brain states" and "normal mental states and processes" in ways not that much different than recreational drugs like alcohol. They obscure psychotic symptoms by "superimposing" an abnormal drug state over other effects. In SSRIs, the small advantages seen in placebo-controlled trials, she suggests, can be attributed to emotional numbing that reduces the intensity of feelings causing the depression and anxiety, at the expense of a fuller experience of the ups and downs of life. The crippling sadness that sometimes follows a reduction in SSRI medication is caused by the chemical dependence the drugs can cause in the brain and withdrawal effects. .... Stress hormones cause the brain to be flooded with the neurotransmitter glutamate, placing it in a state of chronic overstimulation, says Dr. Michael Thase, a professor of psychiatry at UPenn's Perelman School of Medicine. "Glutamate is elevated when you are distressed and aroused—it's also elevated briefly when we're really enthusiastic and up about stuff," he says. "But the kind of elevation of glutamate that's associated with prolonged intractable, severe distress becomes neurotoxic." Over time, brain imaging suggests, this overactivation can cause neurons to shrink and become less connected to one another. Tiny proteins, which support dynamic growth and a healthy brain, dry up in the neurons of the hippocampus, the memory center of the brain, and the prefrontal cortex, where executive functions reside. The spiny arms that form the connections between neurons, known as dendrites and axons, shrivel up. This toxic environment seems to cause a dysregulation of the brain systems needed to perform routine actions. A lack of sleep and an inability to function in daily life creates more stress, releasing more glutamate. The patient spirals downwards.[/I] [HEADING=2][B]No Better Than a Sugar Pill[/B][/HEADING] A few weeks after the Horowitz paper came out, a team of researchers at the U.S. Food and Drug Administration, along with Kirsch, a long-time critic of the drugs from Harvard Medical School, published the most comprehensive analysis to date of all the antidepressant clinical trial data in its files, much of it previously unpublished. The study, which examined 232 placebo-controlled trials of 73,388 patients diagnosed with major depressive disorder, suggested that the active ingredients in 10 of the most popularly prescribed antidepressant medications made a meaningful difference in only 15 percent of the patients who took them, almost always in those patients suffering from the most severe depression. The study, along with others, adds to mounting evidence suggesting that the active ingredients of SSRIs can make the biggest difference in patients who have severe depression, and often are of only marginal utility to those suffering from mild to moderate depression. Why, then, are they so overprescribed? One reason may be that SSRIs are effective for many people not because the drug itself is working but because of the placebo effect. The simple act of treating a patient creates an expectation of healing that results in an improvement in the patient's condition. Previous research has generally found that the placebo effect is successful in 30 to 40 percent of cases of depression—in other words, a third of those who receive a pill or a shot that has no active ingredient get better from the simple fact that they are receiving care and attention from another human being. [/QUOTE]
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Mental Health
The serotonin theory of depression: a systematic umbrella review of the evidence (20 July 2022)
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