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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Snoozy on June 6, 2003, at 11:09:29
I hope someone will be able to help me out or point me to a good resource to learn this stuff.
Can anyone explain anything about how Wellbutrin works (or is supposed to work)?
Second question: I know there's a theory that a lot of meds the body just adjusts to and they're not as effective. Can this go so far as to cause (grrrr- I can't think of the word I want to use) what I'll just call an opposite reaction? For example, a drug that originally caused a side effect of insomnia would eventually cause hypersomnia.
Any information would be very appreciated. I need relief of my idiocy!
Posted by Larry Hoover on June 6, 2003, at 12:43:35
In reply to ? about med chemistry/biology - need help!, posted by Snoozy on June 6, 2003, at 11:09:29
> I hope someone will be able to help me out or point me to a good resource to learn this stuff.
>
> Can anyone explain anything about how Wellbutrin works (or is supposed to work)?This was published in 1995:
"The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated."And yet, in 2001, a study was published showing substantially enhanced serotonin activity with bupropion treatment, through down-regulation of NE activity.
What I conclude is, they still don't know how this drug, or other drugs work. I like the black box theory. You put new stuff (drugs) in the black box (brain), and new stuff comes out (possible remission of depression, side-effects, and so on). No mechanism required. Pure observation.
> Second question: I know there's a theory that a lot of meds the body just adjusts to and they're not as effective.
That's one theory of what we sometimes call "poop out". I think your body will quite naturally try to decrease the effect of any stimulus it receives. It doesn't matter what the stimulus is, your body will try to do things which make "the next time" you experience the stimulus less effective. The first time seems never to be re-experienced. If you extrapolate that process, you get something like poop-out.
>Can this go so far as to cause (grrrr- I can't think of the word I want to use) what I'll just call an opposite reaction?
Are you thinking of "paradoxical reaction"? Like taking a stimulant to calm hyperactivity? Or taking a sedating antihistamine and getting a buzz?
>For example, a drug that originally caused a side effect of insomnia would eventually cause hypersomnia.
There's another way to look at that altogether, as short-term or acute effects, compared with long-term or chronic effects. I think anything's possible, when we're thinking in terms of individual experience. Only when you look at groups of people do you consider likelihood. For the individual with an unusual side-effect, his/her incidence rate is 100%.
> Any information would be very appreciated. I need relief of my idiocy!You're not an idiot. Please. You're asking good questions. And those are questions which will help settle things in your mind, which is a very important aspect of self-care.
I've purposely not gotten into major discussions about your questions, not because I don't want to answer, but because there are so many variables to consider, each of which may or may not have any bearing on your experience.
I'm happy to bounce ideas back and forth with you, but I am going off-line for a short period.
Lar
Posted by Snoozy on June 6, 2003, at 20:28:29
In reply to Re: ? about med chemistry/biology - need help! » Snoozy, posted by Larry Hoover on June 6, 2003, at 12:43:35
Thank you Lar.
I'm unhappy with my lack of biological knowledge. But I have only met one other person as ridiculously squeamish as me, and I had a really creepy biology teacher. So between those things I think I developed a mental block with this stuff.
> And yet, in 2001, a study was published showing substantially enhanced serotonin activity with bupropion treatment, through down-regulation of NE activity.
>
> What I conclude is, they still don't know how this drug, or other drugs work. I like the black box theory. You put new stuff (drugs) in the black box (brain), and new stuff comes out (possible remission of depression, side-effects, and so on). No mechanism required. Pure observation.
>I like this theory too! That's very interesting about the enhanced serotonin activity finding. All these years it was "Wellbutrin doesn't work on serotonin".
> > Second question: I know there's a theory that a lot of meds the body just adjusts to and they're not as effective.
>
> That's one theory of what we sometimes call "poop out". I think your body will quite naturally try to decrease the effect of any stimulus it receives. It doesn't matter what the stimulus is, your body will try to do things which make "the next time" you experience the stimulus less effective. The first time seems never to be re-experienced. If you extrapolate that process, you get something like poop-out.
>When I first started taking AD's in the early 90's, I would sometimes have positive effects for 2-4 months, and then they would go away. I think I actually did call it poop-out when I told my pdocs, but they reacted like I was some freak of medicine. That just doesn't happen! This might be more of an existential question, but I wonder if they really were aware of this phenomenon, and that it was actually fairly common, but they didn't know what else to do with me?
> Are you thinking of "paradoxical reaction"? Like taking a stimulant to calm hyperactivity? Or taking a sedating antihistamine and getting a buzz?
>
Yes, that is the word I was looking for! I've always been puzzled by the stimulants for hyperactivity thing, but that's probably a whole other can of worms! I have had that paradoxical reaction to antihistamines. I've used Benadryl as an occasional sleep aid over the years. Probably 95% of the time it makes me really drowsy, but there have been times where I've had that "buzz". Very strange feeling!> >For example, a drug that originally caused a side effect of insomnia would eventually cause hypersomnia.
>
> There's another way to look at that altogether, as short-term or acute effects, compared with long-term or chronic effects. I think anything's possible, when we're thinking in terms of individual experience. Only when you look at groups of people do you consider likelihood. For the individual with an unusual side-effect, his/her incidence rate is 100%.
>What started me wondering about these things (stop me if you've heard this one before!) was my experience with Wellbutrin and excessive sleepiness. I've been on it for 3 or 4 years, and when I first started, I had the insomnia and irritability. Eventually those subsided. I started having this problem with excessive sleepiness about a year ago. A member of my family has been asking me recently if it could be the Wellbutrin now causing sleepiness. So I've been looking into it, and it seemed unlikely to me (just based on how I feel), and my pdoc thinks it's unlikely as well.
I've had a theory for a few years which I think would fit with the black box theory. Which is that the AD's sometimes work because of the side effects they cause. A few months ago I was reading an article in the paper about studies done on depressed people and sleep. I can't remember the details, but the gist was that a lot of people with depression would get better if you deprived them of sleep (I'm thinking maybe it was an hour of deprivation). And there were observations that depressed people who were allowed to sleep however long they wanted, got somewhat worse. If there's anything to these studies, it would seem possible that it's the insomnia the drugs cause as a side effect that may be helping lift the depression. Unless they're not really viewed as somewhat separate "side" effects, but as integral to the drug.
Thanks again Lar, I really appreciate it!
> > Any information would be very appreciated. I need relief of my idiocy!
>
> You're not an idiot. Please. You're asking good questions. And those are questions which will help settle things in your mind, which is a very important aspect of self-care.
>
> I've purposely not gotten into major discussions about your questions, not because I don't want to answer, but because there are so many variables to consider, each of which may or may not have any bearing on your experience.
>
> I'm happy to bounce ideas back and forth with you, but I am going off-line for a short period.
>
> Lar
Posted by Larry Hoover on June 7, 2003, at 16:56:00
In reply to Re: ? about med chemistry/biology - need help! » Larry Hoover, posted by Snoozy on June 6, 2003, at 20:28:29
> Thank you Lar.
Glad to interact on this.
> I'm unhappy with my lack of biological knowledge. But I have only met one other person as ridiculously squeamish as me, and I had a really creepy biology teacher. So between those things I think I developed a mental block with this stuff.
Whoever said ignorance is bliss didn't have to deal with mental illness.
With respect to your lack of knowledge, being interested in overcoming that, and putting in a little time and effort, and hey! it gets better.
> > What I conclude is, they still don't know how this drug, or other drugs work. I like the black box theory. You put new stuff (drugs) in the black box (brain), and new stuff comes out (possible remission of depression, side-effects, and so on). No mechanism required. Pure observation.
> >
>
> I like this theory too! That's very interesting about the enhanced serotonin activity finding. All these years it was "Wellbutrin doesn't work on serotonin".I don't think that primary receptor binding is the way to perceive any antidepressant. They all affect serotonin, dopamine, norepinephrine, but by obvious direct means, or more commonly, multiple indirect means.
> > > Second question: I know there's a theory that a lot of meds the body just adjusts to and they're not as effective.
> >
> > That's one theory of what we sometimes call "poop out". I think your body will quite naturally try to decrease the effect of any stimulus it receives. It doesn't matter what the stimulus is, your body will try to do things which make "the next time" you experience the stimulus less effective. The first time seems never to be re-experienced. If you extrapolate that process, you get something like poop-out.
> >
>
> When I first started taking AD's in the early 90's, I would sometimes have positive effects for 2-4 months, and then they would go away.I've had that happen myself, more than once.
>I think I actually did call it poop-out when I told my pdocs, but they reacted like I was some freak of medicine. That just doesn't happen!
This is the heart of your concern, isn't it? This institutional trivialization of your experience? My answer is, if your response to meds wasn't in "the big book of medical knowledge", there's something wrong with the book, not with you.
>This might be more of an existential question, but I wonder if they really were aware of this phenomenon, and that it was actually fairly common, but they didn't know what else to do with me?
You're into art vs. science, I'm afraid. The skill with which medication was selected was then, and still is, hunch-based. An educated guess at best, a random act at its worst. Your expectations of them to treat you remained; they didn't know how. I'm sure it's tough being a pdoc with a treatment-resistant patient (though not coming close to how tough it is to *be* that treatment-resistant patient). Initial positive response (maybe we guessed right), followed by nothing thereafter (now what?).
> > Are you thinking of "paradoxical reaction"? Like taking a stimulant to calm hyperactivity? Or taking a sedating antihistamine and getting a buzz?
> >
> Yes, that is the word I was looking for! I've always been puzzled by the stimulants for hyperactivity thing, but that's probably a whole other can of worms! I have had that paradoxical reaction to antihistamines. I've used Benadryl as an occasional sleep aid over the years. Probably 95% of the time it makes me really drowsy, but there have been times where I've had that "buzz". Very strange feeling!Me too. I used to only get the buzz, though. Doctors thought I was lying. Now, more often I get sedation. <shrug>
> > >For example, a drug that originally caused a side effect of insomnia would eventually cause hypersomnia.
> >
> > There's another way to look at that altogether, as short-term or acute effects, compared with long-term or chronic effects. I think anything's possible, when we're thinking in terms of individual experience. Only when you look at groups of people do you consider likelihood. For the individual with an unusual side-effect, his/her incidence rate is 100%.
> >
>
> What started me wondering about these things (stop me if you've heard this one before!) was my experience with Wellbutrin and excessive sleepiness.It's important to know why you're wondering.
> I've been on it for 3 or 4 years, and when I first started, I had the insomnia and irritability. Eventually those subsided. I started having this problem with excessive sleepiness about a year ago. A member of my family has been asking me recently if it could be the Wellbutrin now causing sleepiness. So I've been looking into it, and it seemed unlikely to me (just based on how I feel), and my pdoc thinks it's unlikely as well.
We know nothing, absolutely nothing, about long-term drug reactions. If you're on a med for years, during that time, a multitude of other changes are taking place in your body, mind, and soul. I see no reason that Wellbutrin *isn't* implicated, but nor do I see any obvious reason that it might be. They are correlated; you are taking the drug, and at the same time, you are having this other problem. All you can do is experiment. Try changing the dose. Go off it for a brief period, and restart again. There are various ways to challenge your body to give up the answer. You have to decide if it's worth the trouble to investigate it, or not.
> I've had a theory for a few years which I think would fit with the black box theory. Which is that the AD's sometimes work because of the side effects they cause.
Absolutely, a very real possibility.
> A few months ago I was reading an article in the paper about studies done on depressed people and sleep. I can't remember the details, but the gist was that a lot of people with depression would get better if you deprived them of sleep (I'm thinking maybe it was an hour of deprivation).
A whole night, actually.
> And there were observations that depressed people who were allowed to sleep however long they wanted, got somewhat worse. If there's anything to these studies, it would seem possible that it's the insomnia the drugs cause as a side effect that may be helping lift the depression.
That makes sense.
> Unless they're not really viewed as somewhat separate "side" effects, but as integral to the drug.
Here's another one. We've recently been made aware of a number of drug interactions with antidepressant meds, most often because of effects on liver enzymes. Well, those enzymes weren't just sitting around waiting for antidepressant drugs to metabolize. They have lots of different jobs to do, and the ADs mess around with both the raw material and product concentrations of these different enzymes. Maybe that's why it takes weeks for an AD to work, because it takes weeks to mess up your liver. Maybe the action isn't in the brain at all.
> Thanks again Lar, I really appreciate it!
Happy to bounce ideas around with you.
And, if my intuition served me well (and it seems that it did), your real concerns weren't in the details in what is going on pharmacologically, but in the way you've been patronized by your pdocs. It seemed to me that your motivation in wanting to know the answers to your questiions wasn't just curiosity.
Take care. Gotta go make dinner.
Lar
Posted by Caleb462 on June 7, 2003, at 23:45:31
In reply to ? about med chemistry/biology - need help!, posted by Snoozy on June 6, 2003, at 11:09:29
How wellbutrin works is actually pretty simple, but most people don't know about it.
Bupropion itself is a weak drug, with weak affinities for the dopamine, serotonin and norepinephrine transporters. However... bupropion has *many* ACTIVE metabolites, that also inhibit dopamine/serotonin/norepinephrine reuptake. These metabolites have a long half-life, which allows them to build up in the body over a period of a few weeks. Eventually, you end up with adequate levels of several different chemicals in your body all of which are weak by themselves, but work well together. This is the theory, and it seems to be pretty valid.
Check out this link - http://www.preskorn.com/columns/0001.html
Posted by stjames on June 8, 2003, at 11:42:41
In reply to Re: ? about med chemistry/biology - need help! » Snoozy, posted by Larry Hoover on June 7, 2003, at 16:56:00
We know nothing, absolutely nothing, about long-term drug reactions.
Hmmm,
How long is long enough ? 50+ years on TCA's
seems enough time to at least know something
about long term effects. I will agree that other than TCA's we do not have long term data but I am wondering if 50 years qualifies "long term" for you.
This is the end of the thread.
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