4 ms·

Fun Fact: Selective Serotonin Reuptake Inhibitors, the class of drugs used to treat depression and anxiety disorders by increasing the availability of serotonin

by md224 13y ago

Fun Fact: Selective Serotonin Reuptake Inhibitors, the class of drugs used to treat depression and anxiety disorders by increasing the availability of serotonin, have a mirror opposite: Tianeptine (http://en.wikipedia.org/wiki/Tianeptine http://en.wikipedia.org/wiki/Tianeptine), which acts as a Selective Serotonin Reuptake Enhancer. Incredibly, this drug has also been effective at treating depression. That's right: two classes of drugs with polar opposite first-order effects are used to treat the same disorder, and both of them apparently work.

angersock 13y ago
The molecule looks somewhat obscene.
- jrockway 13y ago
  It might want to get that chlorine looked at.
jes5199 13y ago
I've been meditating on this fact for a while. (I take an SSRI, and I believe that it helps me, but I would love to know why.) I think one possible understanding of depression is that it is a feedback loop - it's a sort of standing wave or Nash equilibrium of patterns of thought causing patterns of behavior causing patterns of sensation causing patterns of emotion that cause patterns of thought, etc. And, perhaps, that just by changing any random variable(s) in that loop (mucking with reuptake, or cognitive behavioral therapy, or any of a whole bunch of other possible changes) has a probability of disrupting the equilibrium and suspending the depression. It's not clear to me how to test this hypothesis, though.
- taway2012 13y ago
  Hmm, check out 'Autopilot' by Andrew Smart. It has some sections about equilibrium etc. And 'On Intelligence' by Jeff Hawkins (very under-rated book imho). Good luck!
  - jes5199 13y ago
    Will do, thanks!
xxpor 13y ago
Both are effective on the same people? Otherwise, it kind of makes sense. If depression is just an imbalance, it may be that there is either too much serotonin or too little.
- jes5199 13y ago
  unfortunately, we don't have good data on which drugs are effective on the same people versus on different people. The clinical trials just aren't set up that way, and there hasn't been a concerted effort to gather that information from the general population.
- chimeracoder 13y ago
  > If depression is just an imbalance, it may be that there is either too much serotonin or too little. Depression is a heterogeneous condition. The "truth" is that it's probably not one, but several conditions with similar symptoms; we just don't have the means to distinguish between them yet. So, we (ie, psychiatrists) try different medications that are known to work on some subset of depression patients, and hope that we find one that fits. I think this is part of why psychiatry gets a bad reputation - even when practiced well, it's an attempt to develop a model for one of the most complicated systems in existence: the human mind & body. When you think about it like that, it's almost a miracle that we're able to do anything given our limited understanding of the way the mind works. (With many medications, we know what chemical effect the medicine has, and we know what subjective effect the medicine has, but we actually don't have a solid understanding of the link between those two). But that's not an indictment of the field as a whole, just an observation of how much more we have yet to learn.
- slurry 13y ago
  The hypothesis that depression comes from a deficiency of serotonin is, from what I understand, no longer considered viable among research psychiatrists[0], although it's still widely believed by practitioners and the general public. Which isn't to say that serotonin-dousing couldn't still be a viable treatment, but your brain doesn't have an ibuprofen deficiency just because Advil takes care of your headaches. [0] http://www.npr.org/blogs/health/2012/01/23/145525853/when-it-comes-to-depression-serotonin-isnt-the-whole-story http://www.npr.org/blogs/health/2012/01/23/145525853/when-it...
joe_the_user 13y ago
The Hawthorne Effect for brains http://en.wikipedia.org/wiki/Hawthorne_effect http://en.wikipedia.org/wiki/Hawthorne_effect
lutusp 13y ago
> and both of them apparently work. I would have said they both appear to work. Recent findings cast doubt on that appearance (PDF warning): http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf http://alphachoices.com/repository/assets/pdf/EmperorsNewDru...
- Dylan16807 13y ago
  Honest question, what's the difference between 'appear' and 'apparently' to you? As far as I use the words, one of their meanings is identical.
  - lutusp 13y ago
    > Honest question, what's the difference between 'appear' and 'apparently' to you? They have similar etymologies, but their current meanings are diverging. An apparent difference may not be visual -- at least, not to the degree that an examination of the word's history would lead one to believe. An appearance of difference still is primarily visual. And yes -- this is to some degree splitting hairs.
    - Dylan16807 13y ago
      Interesting. I don't focus on visuals at all when I say 'appear'. Well, certainly not more than with 'apparent' or other similar words.
      - lutusp 13y ago
        You know, this might just be my personal reading of these words. When I hear "apparent" I don't necessarily think of its connection with the visual, I think "evident", in spite of the etymological connection with the visual Latin root. But to me, "appear" cries out for a visual interpretation, much more so than for "apparent". Again, I think this may be splitting hairs -- I might be making too much of this. "Apparent" in a thesaurus: http://thesaurus.com/browse/apparent http://thesaurus.com/browse/apparent "appear" in a thesaurus: http://thesaurus.com/browse/appear http://thesaurus.com/browse/appear Quite a difference.
refurb 13y ago
It is interesting that two drugs with the opposite mechanisms of action produce the same clinical response. However, you might want to take the description of "reuptake enhancer" with a grain of salt. The mechanism of action (MOA) for drugs is notoriously difficult to determine. The best example of this is Lyrica (Pfizer). The drug was designed to be a GABAase enzyme inhibitor (prevents GABA from being metabolized, increasing it's action). This MOA was pushed during the entire development of Lyrica. It wasn't until the drug hit the market that a researcher finally figured out that it works by modulating the glutamate neurotransmitter. It's effectiveness has nothing at all to do with GABA.
snowwrestler 13y ago
Some kids who act hyperactive can be calmed by giving them a depressant. Other kids who act hyperactive get more hyperactive if given depressants. Giving them stimulants calms them down. Or Some people with heat stroke will improve if given water. Others will get worse. All these paradoxical effects prove is that the human perception of symptoms does not have a direct connection to the root causes of those symptoms. It doesn't mean that stimulants or water (or SSRIs) therefore have questionable efficacies.
- pyre 13y ago
  You could easily write at length on the efficacy of water in putting out fires: You can put out a campfire with water, but adding water to a grease fire does the opposite. So obviously the use of water to put out fires is nothing but hokum!

by md224 13y ago

angersock 13y ago

The molecule looks somewhat obscene.

jrockway 13y ago
It might want to get that chlorine looked at.

jes5199 13y ago

I've been meditating on this fact for a while. (I take an SSRI, and I believe that it helps me, but I would love to know why.) I think one possible understanding of depression is that it is a feedback loop - it's a sort of standing wave or Nash equilibrium of patterns of thought causing patterns of behavior causing patterns of sensation causing patterns of emotion that cause patterns of thought, etc. And, perhaps, that just by changing any random variable(s) in that loop (mucking with reuptake, or cognitive behavioral therapy, or any of a whole bunch of other possible changes) has a probability of disrupting the equilibrium and suspending the depression. It's not clear to me how to test this hypothesis, though.

taway2012 13y ago
Hmm, check out 'Autopilot' by Andrew Smart. It has some sections about equilibrium etc. And 'On Intelligence' by Jeff Hawkins (very under-rated book imho). Good luck!
- jes5199 13y ago
  Will do, thanks!

xxpor 13y ago

Both are effective on the same people? Otherwise, it kind of makes sense. If depression is just an imbalance, it may be that there is either too much serotonin or too little.

jes5199 13y ago
unfortunately, we don't have good data on which drugs are effective on the same people versus on different people. The clinical trials just aren't set up that way, and there hasn't been a concerted effort to gather that information from the general population.
chimeracoder 13y ago
> If depression is just an imbalance, it may be that there is either too much serotonin or too little. Depression is a heterogeneous condition. The "truth" is that it's probably not one, but several conditions with similar symptoms; we just don't have the means to distinguish between them yet. So, we (ie, psychiatrists) try different medications that are known to work on some subset of depression patients, and hope that we find one that fits. I think this is part of why psychiatry gets a bad reputation - even when practiced well, it's an attempt to develop a model for one of the most complicated systems in existence: the human mind & body. When you think about it like that, it's almost a miracle that we're able to do anything given our limited understanding of the way the mind works. (With many medications, we know what chemical effect the medicine has, and we know what subjective effect the medicine has, but we actually don't have a solid understanding of the link between those two). But that's not an indictment of the field as a whole, just an observation of how much more we have yet to learn.
slurry 13y ago
The hypothesis that depression comes from a deficiency of serotonin is, from what I understand, no longer considered viable among research psychiatrists[0], although it's still widely believed by practitioners and the general public. Which isn't to say that serotonin-dousing couldn't still be a viable treatment, but your brain doesn't have an ibuprofen deficiency just because Advil takes care of your headaches. [0] http://www.npr.org/blogs/health/2012/01/23/145525853/when-it-comes-to-depression-serotonin-isnt-the-whole-story http://www.npr.org/blogs/health/2012/01/23/145525853/when-it...

joe_the_user 13y ago

The Hawthorne Effect for brains http://en.wikipedia.org/wiki/Hawthorne_effect http://en.wikipedia.org/wiki/Hawthorne_effect

lutusp 13y ago

> and both of them apparently work. I would have said they both appear to work. Recent findings cast doubt on that appearance (PDF warning): http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf http://alphachoices.com/repository/assets/pdf/EmperorsNewDru...

Dylan16807 13y ago
Honest question, what's the difference between 'appear' and 'apparently' to you? As far as I use the words, one of their meanings is identical.
- lutusp 13y ago
  > Honest question, what's the difference between 'appear' and 'apparently' to you? They have similar etymologies, but their current meanings are diverging. An apparent difference may not be visual -- at least, not to the degree that an examination of the word's history would lead one to believe. An appearance of difference still is primarily visual. And yes -- this is to some degree splitting hairs.
  - Dylan16807 13y ago
    Interesting. I don't focus on visuals at all when I say 'appear'. Well, certainly not more than with 'apparent' or other similar words.
    - lutusp 13y ago
      You know, this might just be my personal reading of these words. When I hear "apparent" I don't necessarily think of its connection with the visual, I think "evident", in spite of the etymological connection with the visual Latin root. But to me, "appear" cries out for a visual interpretation, much more so than for "apparent". Again, I think this may be splitting hairs -- I might be making too much of this. "Apparent" in a thesaurus: http://thesaurus.com/browse/apparent http://thesaurus.com/browse/apparent "appear" in a thesaurus: http://thesaurus.com/browse/appear http://thesaurus.com/browse/appear Quite a difference.

refurb 13y ago

It is interesting that two drugs with the opposite mechanisms of action produce the same clinical response. However, you might want to take the description of "reuptake enhancer" with a grain of salt. The mechanism of action (MOA) for drugs is notoriously difficult to determine. The best example of this is Lyrica (Pfizer). The drug was designed to be a GABAase enzyme inhibitor (prevents GABA from being metabolized, increasing it's action). This MOA was pushed during the entire development of Lyrica. It wasn't until the drug hit the market that a researcher finally figured out that it works by modulating the glutamate neurotransmitter. It's effectiveness has nothing at all to do with GABA.

snowwrestler 13y ago

Some kids who act hyperactive can be calmed by giving them a depressant. Other kids who act hyperactive get more hyperactive if given depressants. Giving them stimulants calms them down. Or Some people with heat stroke will improve if given water. Others will get worse. All these paradoxical effects prove is that the human perception of symptoms does not have a direct connection to the root causes of those symptoms. It doesn't mean that stimulants or water (or SSRIs) therefore have questionable efficacies.

pyre 13y ago
You could easily write at length on the efficacy of water in putting out fires: You can put out a campfire with water, but adding water to a grease fire does the opposite. So obviously the use of water to put out fires is nothing but hokum!