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.
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> 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.
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> 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%.
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> 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
poster:Larry Hoover
thread:231897
URL: http://www.dr-bob.org/babble/20030604/msgs/232229.html