New article on how SSRIs work

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birchswing

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Is this new information?

Anyone want to read it for me and tell me what it says (assume I'm a smarter than average high school graduate)? :)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335176/

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The article says that, to paraphrase the article, SSRI's cause serotonin transporter inhibition, but this inhibition may not be the cause (in part or whole) of why SSRI's work. If this were better understood, it would be easier to create new antidepressants because they could identify new pathways of action to target, listing a bunch at the end. It goes on at length to explain how they shown this questionably causal relationship and the physiological mechanisms that they studied to show the questionable causality. That's a paraphrase of what this article states.

Note: I'm not a medical doctor, and that's a very abbreviated summary from glancing at it quickly.

Just saying bye to you, birchswing. I want to really express my appreciation to you for being an all around standup person who is going through a lot. This post came up as I was logging out since I've decided that I have said all that I need to, otherwise. I want to also reiterate to you that if you decide to stop your benzos with a slow taper, you can do it, it won't be that bad, you may have a return of your original problems, and you don't need to buy that junk from your doctor's pusher to do that. I hope you make it through college someday. You deserve that.
 
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SSRI's cause serotonin transporter inhibition, but this inhibition may not be the cause (in part or whole) of why SSRI's work. If this were better understood, it would be easier to create new antidepressants because they could identify new pathways of action to target, listing a bunch at the end. It goes on at length to explain how they shown this questionably causal relationship and the physiological mechanisms that they studied to show the questionable causality.

Note: I'm not a medical doctor, and that's a very abbreviated summary from glancing at it quickly.

Just saying bye to you, birchswing. I want to really express my appreciation to you for being an all around standup person who is going through a lot. This post came up as I was logging out since I've decided that I have said all that I need to, otherwise. I want to also reiterate to you that if you decide to stop your benzos with a slow taper, you can do it, it won't be that bad, you may have a return of your original problems, and you don't need to buy that junk from your doctor's pusher to do that. I hope you make it through college someday. You deserve that.
Thank you very much. I really appreciate it. I am right now part-time in college. One step at a time. One course at a time (if they keep letting me do it that way, I've slipped under the radar so far . . .). Best of luck to you. I appreciate the confidence with regard to a benzo taper. Sorry I didn't respond to your other question asking about elaborating on what part of course materials I found obfuscating. I wrote a long response and then even went back to the textbook I found so confounding to give a quote as an example, and I realized the textbook did make sense—although that was reading a small bit at a time, which is easier than reading a lot at once, esp when the material is dense So, I was a bit flummoxed that my original point didn't stand. I was going to wait till I get past this exam I have on Tuesday to write a longer response, but that was probably the gist of it anyway.

Good luck to you in your academic pursuits, as well!
 
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SSRI's cause serotonin transporter inhibition, but this inhibition may not be the cause (in part or whole) of why SSRI's work. If this were better understood, it would be easier to create new antidepressants because they could identify new pathways of action to target, listing a bunch at the end. It goes on at length to explain how they shown this questionably causal relationship and the physiological mechanisms that they studied to show the questionable causality.

Note: I'm not a medical doctor, and that's a very abbreviated summary from glancing at it quickly.

Just saying bye to you, birchswing. I want to really express my appreciation to you for being an all around standup person who is going through a lot. This post came up as I was logging out since I've decided that I have said all that I need to, otherwise. I want to also reiterate to you that if you decide to stop your benzos with a slow taper, you can do it, it won't be that bad, you may have a return of your original problems, and you don't need to buy that junk from your doctor's pusher to do that. I hope you make it through college someday. You deserve that.

Despite how depression is described in pharm ads, it seems to be quite obvious that serotonin "insufficiency" in the brain doesn't seem to be the main etiology of depression. There have been mouse models developed with severe serotonin depletion and those mice don't appear to develop depression at any significantly higher rates than normal mice. As you say, the serotonin hypothesis is likely, at best, an oversimplification of what's going on and at worst a complete red herring that obfuscates the true downstream effects of SSRIs and other antidepressants.
 
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So this is essentially the same old "we know it works but we don't know why" ?
 
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do we know it works? it can all be explained by placebo effects
Idk. I take it and I can function a hell of a lot more like a normal human being than I do without it. I'm sure there are real studies that I could find if I dig but I'm lazy and tired. At the end of the day I'm quite confident I'd be dead without them, placebo or not I'm still gonna keep taking them
 
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Grumble grumble at people saying it says what we already know which is that we don't know anything. It seems to be quite different, and it seems to be saying a lot. Granted I don't understand it, but for one thing it seems to be focusing on astrocytes instead of neurons. Isn't that a huge change in and of itself? And I don't even know what astrocytes are, but I know they're not neurons.
 
Saw someone recently who also saw their PCP. He was mad and uttered epithets, and questioned the Pt why I had to use so many medications (for resistant depression) and further explains that the Pt didn't need all of those medications because they all did the same thing.
 
More like, "it usually doesn't really do anything, but when it does we don't know why"
yeah! Science, bitch !
Idk. I take it and I can function a hell of a lot more like a normal human being than I do without it. I'm sure there are real studies that I could find if I dig but I'm lazy and tired. At the end of the day I'm quite confident I'd be dead without them, placebo or not I'm still gonna keep taking them
Grumble grumble at people saying it says what we already know which is that we don't know anything. It seems to be quite different, and it seems to be saying a lot. Granted I don't understand it, but for one thing it seems to be focusing on astrocytes instead of neurons. Isn't that a huge change in and of itself? And I don't even know what astrocytes are, but I know they're not neurons.
I love the central nervous system! So many people seem to think we are a "soft science" when actually the mind/body/social interaction is one of the most complex systems that we could study. Of course, that does play out in all other aspects of medicine, but many of them act as though it doesn't exist. Of course, as we well know, that is just a defense mechanism ;) on their part. Only the truly brave can embrace the uncertainty of our field IMO. To be fair though, slicing people open and removing organs might be a bit scary, too! I was too clumsy to ever consider that. Oops! in the OR would not be good. When I drop my pen during the middle of a diagnostic interview, it is actually an opportunity to build rapport. :D
 
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I love the central nervous system! So many people seem to think we are a "soft science" when actually the mind/body/social interaction is one of the most complex systems that we could study. Of course, that does play out in all other aspects of medicine, but many of them act as though it doesn't exist. Of course, as we well know, that is just a defense mechanism ;) on their part. Only the truly brave can embrace the uncertainty of our field IMO. To be fair though, slicing people open and removing organs might be a bit scary, too! I was too clumsy to ever consider that. Oops! in the OR would not be good. When I drop my pen during the middle of a diagnostic interview, it is actually an opportunity to build rapport. :D
I've only recently come to respect how significantly mental stress affects my body. I've had physical manifestations of anxiety that to me could not possibly be explained by stressors but then that turned out to be the explanation once the stressor disappeared (and after extensive medical testing ruling out other factors). Part of the misperception was that my initial introduction to mental health was that anxiety was exactly like any other disease, and that SSRIs were exactly like the insulin a diabetic needed. Now I realize that the disease model for me is in having hypersensitivity to triggers--mental and physical. The mental stressors become physical maladies and, in my case, my body also is dysautonomic so that the way I respond to the simple act of standing is grossly exaggerated. I've gotten quite good at not responding with anxiety to abnormal autonomic responses. I still, though, respond quite physically to mental stressors. And that's a different physical response (shaking, not eating, not sleeping). I was often the last to realize it was anxiety causing such symptoms because they can be so severe it's hard to believe that they can be caused by life situations, but it's happened enough now that I realize it's the case. The other complicator for me is that it's hard to differentiate between withdrawal and anxiety symptoms, but either way stress triggers a body response in ways that seem unbelievable.
 
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Do you prescribe them?
yes! And in the past 5 years I have only had one case where I have been absolutely convinced that the SRI did something. 200mg sertraline in a patient w/ tetrabenazine-induced depression. The patient did not know he was taking an antidepressant. I started the trial as the patient was extreme distraught, tearful, prone to crying and wailing spells, and having suicidal thoughts. After about 8weeks on the drug and a few weeks at 200mg the patient was for the first time sitting in a chair, reading, and smiling. He told me he still felt depressed but wasn't as bothered by it anymore. He didn't know he was on the drug, and his social and medical situation hadn't change and he was still taking the tetrabenazine.

Other than that I have never been able to convince myself that SRI responses I have seen are more than placebo. It's nice to see patients respond marvellously to homeopathic doses of zoloft after a week in the primary care clinic I consult in. Not that I'm knocking the placebo effect. If anything, we should look at how we can maximize these effects in clinical practice. It's indisputable that the majority of response is placebo effect if you look at the RCTs and systematic review. This is why drug companies are devoting large sums to try and do something about the pesky placebo effect that makes their drugs look bad, including advocating for the end of placebo-controlled trials as "unethical". What is a matter of debate is whether any additional difference is a factor of SRIs having more efficacy in severe depressive states (which seems unlikely) vs placebo being less effective with more depressive states (which has been reported for many years), whether SRIs are "active placebos" vs "inert placebos", whether the participants in clinical trial are too well to benefit from SRIs etc.

I had more faith in the TCAs and MAOIs but there is some suggestion that you just get an active placebo effect because of the terrible side-effects. Also the power of MAOIs "if you eat cheese - you'll die!" may also convey something about the powerful therapeutic properties of the drug.

Really wish there was a lot more research on placebo effects, both clinically, psychologically, and neurobiologically. The stuff I've read is pretty fascinating
 
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I agree about placebos being interesting someone was telling me there are several European countries where it is still acceptable for a mainstream physician to knowingly prescribe a literal placebo pill for all sorts of stuff. Not sure if it's true as I haven't looked into it.

Indian guy i knew in college claimed all of his mom's social circle in India would go to docs and get rainbow handfuls of what were apparently sugar pills.
 
I wonder if you could test placebos more easily in very young children since we lie to them all the time anyway (in order to manipulate them into doing what we want, e.g., God/Santa Claus is watching you, the Easter Bunny left you this, if you eat spinach you'll be strong like Popeye, etc.). When I was a very young child and was scared of flying my dad would give me fruit Mentos. We saved the pink one for take-off which he said was the most powerful in protecting me. It seems like a lot of psychological experiments are conducted on children, anyway. If you're just doing blue-skies research on the effect of telling someone a pink pill will make them happy it doesn't seem much more manipulative than things like the Strange experiment. And it seems like a young child would be much less concerned about whether it's medicine or candy. For what it's worth at my current age there aren't enough pink Mentos in the world to get me to fly.
 
Bad-Elf-on-the-Shelf.jpg
 
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yes! And in the past 5 years I have only had one case where I have been absolutely convinced that the SRI did something. 200mg sertraline in a patient w/ tetrabenazine-induced depression. The patient did not know he was taking an antidepressant. I started the trial as the patient was extreme distraught, tearful, prone to crying and wailing spells, and having suicidal thoughts. After about 8weeks on the drug and a few weeks at 200mg the patient was for the first time sitting in a chair, reading, and smiling. He told me he still felt depressed but wasn't as bothered by it anymore. He didn't know he was on the drug, and his social and medical situation hadn't change and he was still taking the tetrabenazine.

Other than that I have never been able to convince myself that SRI responses I have seen are more than placebo. It's nice to see patients respond marvellously to homeopathic doses of zoloft after a week in the primary care clinic I consult in. Not that I'm knocking the placebo effect. If anything, we should look at how we can maximize these effects in clinical practice. It's indisputable that the majority of response is placebo effect if you look at the RCTs and systematic review. This is why drug companies are devoting large sums to try and do something about the pesky placebo effect that makes their drugs look bad, including advocating for the end of placebo-controlled trials as "unethical". What is a matter of debate is whether any additional difference is a factor of SRIs having more efficacy in severe depressive states (which seems unlikely) vs placebo being less effective with more depressive states (which has been reported for many years), whether SRIs are "active placebos" vs "inert placebos", whether the participants in clinical trial are too well to benefit from SRIs etc.

I had more faith in the TCAs and MAOIs but there is some suggestion that you just get an active placebo effect because of the terrible side-effects. Also the power of MAOIs "if you eat cheese - you'll die!" may also convey something about the powerful therapeutic properties of the drug.

Really wish there was a lot more research on placebo effects, both clinically, psychologically, and neurobiologically. The stuff I've read is pretty fascinating

I don't have any experience personally with SSRIs and depression, but I did take an SSRI for ~6 months for anxiety and will say that it completely destroyed any anxiety that I had within a couple of weeks. It was awesome. I'm less with familiar with the mechanisms surrounding SSRI impact on anxiety - i.e., if it's less hand wavy than the impact on depression - but if that was placebo effect then I have gained a newfound respect for placebos.
 
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well anxiety is even more nebulous than depression (and really there is so much overlap between DSM GAD and MDD that is almost ridiculous to see them as distinct) but placebos are very impressive and often people talk about them disparagingly (which is why placebos aren't as effective as they once were) but really the power of suggestion is well - powerful! This is probably at the heart for a lot of psychotherapy too.

I do like this theory of antidepressant action too: http://bjp.rcpsych.org/content/195/2/102
 
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Splik, not just DSM criteria for MDD and Anxiety disorders, but often clouding good clinical evaluations and judgments citing people have Dementia or ADHD when this isn't necessarily true.
 
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I may be in the minority of patients here, but I actually prefer an antidepressant to not work completely on me, which is one of the reasons why I take the lowest dose possible that still gives some clinically noticeable effects, but still doesn't lift the depression completely. I pretty much need to be at the 'I'm at risk of doing something stupid, and this is starting to get scary' type level of depression, before I'll agree to take an AD. I just prefer to still be feeling the depression to a safe degree in Psychotherapy so I can work through the feelings of depression. I'm the same with anti psychotics, just give me enough to turn the volume down enough for me to concentrate in therapy, and then I can learn non medication ways of dealing with stuff.
 
well anxiety is even more nebulous than depression (and really there is so much overlap between DSM GAD and MDD that is almost ridiculous to see them as distinct) but placebos are very impressive and often people talk about them disparagingly (which is why placebos aren't as effective as they once were) but really the power of suggestion is well - powerful! This is probably at the heart for a lot of psychotherapy too.

I do like this theory of antidepressant action too: http://bjp.rcpsych.org/content/195/2/102

Interesting article - thanks for sharing.
 
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