4 ms·

Something Huberman said on his podcast about alcohol is that the anti-depressive effects of SSRIs are not due to serotonin, but due to neuroplasticity.

by pgt 4y ago

jnovek 4y ago
Can you elaborate on this, please? I’ve never heard this hypothesis and I don’t totally understand what it means. Are you saying that SSRIs trigger changes in the brain? What changes? Why do they trigger these changes? Genuinely curious.
- snek_case 4y ago
  Yes, SSRIs trigger change in the brain. That's why the effect is not instant when you start taking the pill, the change needs some time to start to happen. In particular, it's believed that depressed people have lower levels of neuroplasticity. Their brains are less able to adapt to their current circumstances and they're stuck in negative thought patterns. SSRIs help increase the brain's ability to grow new connections and help the brain adapt, which helps you get out of negative thought patterns. If you're interested enough to watch a whole talk about this (you can jump to around 26 minutes): https://www.youtube.com/watch?v=k2AdebIbx5Y https://www.youtube.com/watch?v=k2AdebIbx5Y
  - loceng 4y ago
    Leading also to an increase in rate of suicide compared to placebo, and arguably increased homicide as well; guns being the misdirection narrative. Edit to add: Downvotes even though in 2015 the FDA required "black box" suicide warnings on SSRIs because what I'm saying is true?
    - snek_case 4y ago
      There's this narrative going around that antidepressants bad because medication bad, psychiatric industry evil, modern medicine bad, yadda yadda yadda. The problem is, everybody's brain chemistry is unique and different, because our genetics are different. Some antidepressants work for some people and not others. I've personally tried 5 of them. Only one of them worked on me, and it had some unfortunate side-effects (messed with my sleep). My ex-girlfriend used a different antidepressant (Zoloft). Personally, I've tried Zoloft and all it did was make me sleepy all the time, but I've found Lexapro was quite effective and useful for getting my life back on track. The way efficacy studies are done right now is, we measure the average effect on a group of people. That's doesn't really make sense when you think that everyone's genetics are unique and the antidepressant could be making some people better and some people worse, right? Maybe half the group feels better, but a quarter of the group becomes suicidal. Then on average, you see scores going up, you see the drug is beneficial on average... It would be kind of like giving everyone in a group a prescription for eyeglasses, all with the same prescription, and measuring that on average, participants can read better with the eyeglasses than not. In some ways, modern medicine is still very primitive. Flooding the whole brain with a chemical and hoping that it interacts with the right receptors and has a beneficial effect without too many side effects if you have the right genetics is very primitive. It's the best we have right now though, and antidepressants in general are probably more helpful than not, but yes, people SHOULD be aware that they might very well not work on them.
      - loceng 4y ago
        "It's the best we have right now though, and antidepressants in general are probably more helpful than not, but yes, people SHOULD be aware that they might very well not work on them." MDMA, for example, seems far superior than anything else on the market - and what it does is simply causes the brain to release more serotonin than it normally would; SSRIs (etc) don't do that, they change how the brain actually functions. Your argument that "in general are probably more helpful than not" also then means you are okay that MORE PEOPLE kill themselves taking the SSRIs than would have otherwise - so you're okay with people dying, when rather there are alternatives - they just aren't mainstream because they haven't been promoted and marketed to doctors, nor advertised to manipulate people via ads by the pharmaceutical industry; I don't think that's acceptable or reasonable.
        snek_case 4y ago
        As someone who's almost certainly used MDMA longer than you have, just no... MDMA is know to commonly cause depressive crashes. It's no panacea, it's a drug with it's own tradeoffs just like antidepressants. Do a google search for "suicide Tuesday".
        loceng 4y ago
        As someone who uses the very shallow metric of "length of use" - thinking it is somehow a strong argument point, I'm guessing my judgement, critical thinking, understanding is greater than yours. The "tradeoff" is MORE PEOPLE die of suicide with SSRIs (et al) being prescribed than if they weren't allowed to be prescribed. "MDMA is know to commonly cause depressive crashes" is another shallow-narrow scope counter argument you put forward. A "depressive crash" - and arguably, in the right container with the right guidance can be avoided, and in fact is underlying depressed state that a person is connecting to - is not akin to people literally killing themselves from SSRIs. '"Suicide Tuesday" is the nickname given to the trend for people who use xtc all weekend committing suicide when they fully come down from the high on Tuesday.' You're bringing in abuse, an excess of something, as a supportive argument point? People also accidentally or purposefully recklessly drink too much or take too many opiates - perhaps in hopes they die. You also put forward a straw man argument - I never said MDMA was a panacea. Are you aware of the MAPS.org FDA approved clinical trials for MDMA-assisted psychotherapy for veterans with an average of 17.5 treatment resistant PTSD, where after just 2-3 sessions, in 1 year time 80% no longer qualified for a PTSD diagnosis vs. the placebo group where 80% had no improvement? Using therapeutic doses of 100-120mg. Do you know what the efficacy of SSRIs are, what the tradeoff your arguing and in support of? 3-7% better than placebo depending on the research you look at - and you kill people (through suicide and homicide) that otherwise wouldn't have died; and this happens at prescribed doses, not abusing the medications.
    - heavyset_go 4y ago
      I've written about this in the past a lot[1], but 5HT2C activation is the primary cause of suicidal ideation when starting SSRIs. Once 5HT2C is downregulated after a few weeks, the feelings and akathisia caused by 5HT2C activation dissipate, as does suicidal ideation. 5HT2C activation can be very, very uncomfortable, and can exacerbate depression, anxiety and suicidal thoughts. Downregulation results in an equilibrium where those feelings and symptoms are relieved over time, however. [1] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Heavyset_go%205ht2c&sort=byPopularity&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
      - loceng 4y ago
        So your argument is, if your claim is true - and if it's true in all cases or not - that those excess, unnecessary suicides, will happen within the first "few weeks" - and then that's acceptable to you that more people kill themselves on SSRIs (etc)? And there are other options - far better, far less harmful options do indeed exist - but the medical-pharmaceutical industrial complex hasn't made them widely known or available because getting people dependant on (due to severe withdrawal in most cases, another thing they lied about; like how it was lied about the new opiates weren't addictive to get them mass prescribed) medications that are patented allows pharma to make an increasingly large recurring revenue stream; and who cares if X% of MORE people kill themselves than otherwise would have if you're now making many $ billions per month - and as a doctor all you need to do to "help" someone, and the only competency and knowledge you need, the most shallow complexity you need to understand, is to write a prescription for someone? And then the other side of the coin is the increased homicide, and the responsibility that people they should take on if they want these medications available - on top of being in part responsible for the increased suicides - are all of the mass shooting deaths; let alone the increased ideology and antisocial behaviour we have in society could arguably be heavily influenced by these medications as well, and the widespread harm that causes to society.
- twic 4y ago
  It's been decades since i studied this stuff, but i remember there being a very promising line of work on the connections of the growth factors BDNF and NGF, which promote neuroplasticity, to depression. Seems it's still being worked on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/ https://pubmed.ncbi.nlm.nih.gov/30235967/ https://pubmed.ncbi.nlm.nih.gov/30235967/
- heavyset_go 4y ago
  The theory is that hippocampal neurogenesis could be a factor in the treatment of depression. The hypothesis is based on the fact that effective antidepressants trigger neurogenesis, and not all antidepressants have the same mechanisms of action.

Something Huberman said on his podcast about alcohol is that the anti-depressive effects of SSRIs are not due to serotonin, but due to neuroplasticity.

by pgt 4y ago

Something Huberman said on his podcast about alcohol is that the anti-depressive effects of SSRIs are not due to serotonin, but due to neuroplasticity.

jnovek 4y ago

Can you elaborate on this, please? I’ve never heard this hypothesis and I don’t totally understand what it means. Are you saying that SSRIs trigger changes in the brain? What changes? Why do they trigger these changes? Genuinely curious.

snek_case 4y ago
Yes, SSRIs trigger change in the brain. That's why the effect is not instant when you start taking the pill, the change needs some time to start to happen. In particular, it's believed that depressed people have lower levels of neuroplasticity. Their brains are less able to adapt to their current circumstances and they're stuck in negative thought patterns. SSRIs help increase the brain's ability to grow new connections and help the brain adapt, which helps you get out of negative thought patterns. If you're interested enough to watch a whole talk about this (you can jump to around 26 minutes): https://www.youtube.com/watch?v=k2AdebIbx5Y https://www.youtube.com/watch?v=k2AdebIbx5Y
- loceng 4y ago
  Leading also to an increase in rate of suicide compared to placebo, and arguably increased homicide as well; guns being the misdirection narrative. Edit to add: Downvotes even though in 2015 the FDA required "black box" suicide warnings on SSRIs because what I'm saying is true?
  - snek_case 4y ago
    There's this narrative going around that antidepressants bad because medication bad, psychiatric industry evil, modern medicine bad, yadda yadda yadda. The problem is, everybody's brain chemistry is unique and different, because our genetics are different. Some antidepressants work for some people and not others. I've personally tried 5 of them. Only one of them worked on me, and it had some unfortunate side-effects (messed with my sleep). My ex-girlfriend used a different antidepressant (Zoloft). Personally, I've tried Zoloft and all it did was make me sleepy all the time, but I've found Lexapro was quite effective and useful for getting my life back on track. The way efficacy studies are done right now is, we measure the average effect on a group of people. That's doesn't really make sense when you think that everyone's genetics are unique and the antidepressant could be making some people better and some people worse, right? Maybe half the group feels better, but a quarter of the group becomes suicidal. Then on average, you see scores going up, you see the drug is beneficial on average... It would be kind of like giving everyone in a group a prescription for eyeglasses, all with the same prescription, and measuring that on average, participants can read better with the eyeglasses than not. In some ways, modern medicine is still very primitive. Flooding the whole brain with a chemical and hoping that it interacts with the right receptors and has a beneficial effect without too many side effects if you have the right genetics is very primitive. It's the best we have right now though, and antidepressants in general are probably more helpful than not, but yes, people SHOULD be aware that they might very well not work on them.
    - loceng 4y ago
      "It's the best we have right now though, and antidepressants in general are probably more helpful than not, but yes, people SHOULD be aware that they might very well not work on them." MDMA, for example, seems far superior than anything else on the market - and what it does is simply causes the brain to release more serotonin than it normally would; SSRIs (etc) don't do that, they change how the brain actually functions. Your argument that "in general are probably more helpful than not" also then means you are okay that MORE PEOPLE kill themselves taking the SSRIs than would have otherwise - so you're okay with people dying, when rather there are alternatives - they just aren't mainstream because they haven't been promoted and marketed to doctors, nor advertised to manipulate people via ads by the pharmaceutical industry; I don't think that's acceptable or reasonable.
      - snek_case 4y ago
        As someone who's almost certainly used MDMA longer than you have, just no... MDMA is know to commonly cause depressive crashes. It's no panacea, it's a drug with it's own tradeoffs just like antidepressants. Do a google search for "suicide Tuesday".
        loceng 4y ago
        As someone who uses the very shallow metric of "length of use" - thinking it is somehow a strong argument point, I'm guessing my judgement, critical thinking, understanding is greater than yours. The "tradeoff" is MORE PEOPLE die of suicide with SSRIs (et al) being prescribed than if they weren't allowed to be prescribed. "MDMA is know to commonly cause depressive crashes" is another shallow-narrow scope counter argument you put forward. A "depressive crash" - and arguably, in the right container with the right guidance can be avoided, and in fact is underlying depressed state that a person is connecting to - is not akin to people literally killing themselves from SSRIs. '"Suicide Tuesday" is the nickname given to the trend for people who use xtc all weekend committing suicide when they fully come down from the high on Tuesday.' You're bringing in abuse, an excess of something, as a supportive argument point? People also accidentally or purposefully recklessly drink too much or take too many opiates - perhaps in hopes they die. You also put forward a straw man argument - I never said MDMA was a panacea. Are you aware of the MAPS.org FDA approved clinical trials for MDMA-assisted psychotherapy for veterans with an average of 17.5 treatment resistant PTSD, where after just 2-3 sessions, in 1 year time 80% no longer qualified for a PTSD diagnosis vs. the placebo group where 80% had no improvement? Using therapeutic doses of 100-120mg. Do you know what the efficacy of SSRIs are, what the tradeoff your arguing and in support of? 3-7% better than placebo depending on the research you look at - and you kill people (through suicide and homicide) that otherwise wouldn't have died; and this happens at prescribed doses, not abusing the medications.
  - heavyset_go 4y ago
    I've written about this in the past a lot[1], but 5HT2C activation is the primary cause of suicidal ideation when starting SSRIs. Once 5HT2C is downregulated after a few weeks, the feelings and akathisia caused by 5HT2C activation dissipate, as does suicidal ideation. 5HT2C activation can be very, very uncomfortable, and can exacerbate depression, anxiety and suicidal thoughts. Downregulation results in an equilibrium where those feelings and symptoms are relieved over time, however. [1] https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=Heavyset_go%205ht2c&sort=byPopularity&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
    - loceng 4y ago
      So your argument is, if your claim is true - and if it's true in all cases or not - that those excess, unnecessary suicides, will happen within the first "few weeks" - and then that's acceptable to you that more people kill themselves on SSRIs (etc)? And there are other options - far better, far less harmful options do indeed exist - but the medical-pharmaceutical industrial complex hasn't made them widely known or available because getting people dependant on (due to severe withdrawal in most cases, another thing they lied about; like how it was lied about the new opiates weren't addictive to get them mass prescribed) medications that are patented allows pharma to make an increasingly large recurring revenue stream; and who cares if X% of MORE people kill themselves than otherwise would have if you're now making many $ billions per month - and as a doctor all you need to do to "help" someone, and the only competency and knowledge you need, the most shallow complexity you need to understand, is to write a prescription for someone? And then the other side of the coin is the increased homicide, and the responsibility that people they should take on if they want these medications available - on top of being in part responsible for the increased suicides - are all of the mass shooting deaths; let alone the increased ideology and antisocial behaviour we have in society could arguably be heavily influenced by these medications as well, and the widespread harm that causes to society.
twic 4y ago
It's been decades since i studied this stuff, but i remember there being a very promising line of work on the connections of the growth factors BDNF and NGF, which promote neuroplasticity, to depression. Seems it's still being worked on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174655/ https://pubmed.ncbi.nlm.nih.gov/30235967/ https://pubmed.ncbi.nlm.nih.gov/30235967/
heavyset_go 4y ago
The theory is that hippocampal neurogenesis could be a factor in the treatment of depression. The hypothesis is based on the fact that effective antidepressants trigger neurogenesis, and not all antidepressants have the same mechanisms of action.