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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by mgrueni on September 7, 2001, at 5:46:18
Uhm, first let me say that I don`t mean to be impolite by directly asking a particular poster. Of course I would appreciate everyone`s explanation. It´s just that I thought this special question would be best adressed to you (as you are a pharmacist), Cam.
I am a pharmacist assistant, so I do know the basics about how antidepressants work.
My question is about Effexor.
I fully understand the mechanism of Effexor inhibiting the serotonine and noradrenaline (or is that "norepinephrine" in english?) re-uptake.
I roughly know what effects noradrenaline has on the sympathetic-system (blood pressure increase, metabolism increase and so on...)and why that is so.I am asking for a particular reason. One of my friends is taking Effexor XR (150mg/day) and has massive sleep disorder (*broken* sleep plus waking up at 5:00 am and couldn`t get back to sleep again)
Now I wonder, whether Effexor could be the cause of this problems (or at least increasing them, as he had this problems before, but they got worse under Effexor)
I was trying to figure out the *why* of some of Effexor`s possible side-effects and interactions with other drugs on the basis of my little knowlegde, but, I could use a little help with that.Could you please explain me:
* what exactly does Serotonine do (physical and psychological effects)
* what effects does noradrenaline has on one`s psyche?And, what do you think about Kava-Kava to help his sleep disorder? I`ve heard Kava-Kava is discussed to have an effect on Serotonine re-uptake and being metabolized by CYP2D6 ?
Now, if that is true (I am not sure) that would mean Kava-Kava could cause a toxic Serotonine level - which would be as bad as combinating Effexor with MAO-inhibitors?
Thank you very muchMicha
PS: You might wonder, why I am not asking my boss. I am on holidays at the moment and the only way to do so would be to phone him, but I never know when would be a good time, as he`s usually very busy.
Posted by Cam W. on September 7, 2001, at 9:53:39
In reply to Cam, could you please explain me something?, posted by mgrueni on September 7, 2001, at 5:46:18
Micha - For years, scientists have been breaking the brain down into smaller and smaller parts to see how it works (reductionism). Now that they have got down to neurotransmitters, second messenger systems, and especially gene transcription.
I like to use the "automobile as human body" analogy. It he brain were the engine, then when we get down to the neurotransmitter level, we can equate (say) serotonin to spark plugs of the electrical system. Now, an isolated spark plug does not do much; it does not tell us how the car runs. We have to step back from the spark plug to see how it works in relation to the rest of parts it attaches to (and also what those other parts attach to).
Of course, the brain is a much more complex piece of machinery than a car, and the analogy is far from perfect; but I hope you can see what I am trying to say. As for the functions of serotonin and norepinephrine, I will give an oversimplified answer of their effects. A far more in depth explanation can be found at the following website:
http://www.acnp.org/g4/4thgen.php
Serotonin: Involved in: sleep initiation, impulsivity, mood modulation, pain modulation, modulation of aggression, control of anxiety, maintenance of alertness.
Norepinephrine: Involved in: sleep maintenance, mood modulation, energy, interest, vigilance, self-perception.
Serotonin + Norepinephrine: Involved in: anxiety and irritability.
Serotonin + Norepinephrine + Dopamine: Involved in: mood, emotion, and cognitive function.
As for the pharmacology of Kava Kava, I have no idea. I have never seen serotonin syndrome result from the use of an SSRI and Kava Kava. I have seen some fairly nasty, flaking rashes result from the use of high doses of Kava Kava, over a long period of time, though.
I hope that this (and the link) are of some use to you. - Cam
Posted by mgrueni on September 7, 2001, at 13:24:21
In reply to Re: Cam, could you please explain me something?, posted by Cam W. on September 7, 2001, at 9:53:39
Hello Cam,
< I like to use the "automobile as human body" analogy. It he brain were the engine, then when we get down to the neurotransmitter level, we can equate (say) serotonin to spark plugs of the electrical system. Now, an isolated spark plug does not do much; it does not tell us how the car runs. We have to step back from the spark plug to see how it works in relation to the rest of parts it attaches to (and also what those other parts attach to). >
Yes, I`ve heard of this analogy and it seems quite logical to me. Thanks for reminding me of it (I forgot *so* much of what I learnt at pharmacy school) :o)
< Serotonin: Involved in: sleep initiation, impulsivity, mood modulation, pain modulation, modulation of aggression, control of anxiety, maintenance of alertness. Norepinephrine: Involved in: sleep maintenance, mood modulation, energy, interest, vigilance, self-perception Serotonin + Norepinephrine + Dopamine: Involved in: mood, emotion, and cognitive function. >
Ah, that were the basics I was looking for - you wouldn`t believe how difficult it is to find some useful answers to medical related questions in german language on the net. All sites which possibly would give such answers are key-word protected (doctors only) :o(
A far more in depth explanation can be found at the following website:
http://www.acnp.org/g4/4thgen.php
It will take me some time to read it, but this also seems to be very useful.
< As for the pharmacology of Kava Kava, I have no idea. I have never seen serotonin syndrome result from the use of an SSRI and Kava Kava. I have seen some fairly nasty, flaking rashes result from the use of high doses of Kava Kava, over a long period of time, though. >
Yes? Rashes? That`s news to me.
But, I think I will not recommend Kava Kava in combination with Effexor, as long as there are no new reasearches which say that it definitely isn`t dangerous - better too careful than too experimental. It seems, valerian is working quite good on my friend, so I hope that will solve the problem.
< I hope that this (and the link) are of some use to you. - Cam >Yes, thank you :o)
Micha
PS: please excuse my rather formal and brief reply (unusual for me....) but I have a very bad headache at the moment, and can hardly concentrate on anything.
Posted by Adam on September 7, 2001, at 14:55:03
In reply to Re: Cam, could you please explain me something?, posted by Cam W. on September 7, 2001, at 9:53:39
In defense of reductionism (as opposed to oversimplification, which one might call "naive reductionism"), looking only at a spark plug will not tell you much about an engine, but looking at an engine without knowing about spark plugs would leave you pretty mystified as to how the damn thing works. The key is to find all the little bits and pieces without losing sight of the "big picture". Most good scientists know they work with imperfect models and incomplete pictures, and do the best they can with what they've got. If they're responsible, they look at the excellent summary you gave, seeing it as a means to a better end, a framework upon which to build a more complete, and, in all likelihood, more accurate picture.
Sadly, being people, we sometimes get a little too fond of our models, flawed as they are, and that can lead one down many a blind alley. Reductionism is perilous if it is seen as an end rather than a means, but, used wisely, it is a powerful approach.
> Micha - For years, scientists have been breaking the brain down into smaller and smaller parts to see how it works (reductionism). Now that they have got down to neurotransmitters, second messenger systems, and especially gene transcription.
>
> I like to use the "automobile as human body" analogy. It he brain were the engine, then when we get down to the neurotransmitter level, we can equate (say) serotonin to spark plugs of the electrical system. Now, an isolated spark plug does not do much; it does not tell us how the car runs. We have to step back from the spark plug to see how it works in relation to the rest of parts it attaches to (and also what those other parts attach to).
>
> Of course, the brain is a much more complex piece of machinery than a car, and the analogy is far from perfect; but I hope you can see what I am trying to say. As for the functions of serotonin and norepinephrine, I will give an oversimplified answer of their effects. A far more in depth explanation can be found at the following website:
>
> http://www.acnp.org/g4/4thgen.php
>
> Serotonin: Involved in: sleep initiation, impulsivity, mood modulation, pain modulation, modulation of aggression, control of anxiety, maintenance of alertness.
>
> Norepinephrine: Involved in: sleep maintenance, mood modulation, energy, interest, vigilance, self-perception.
>
> Serotonin + Norepinephrine: Involved in: anxiety and irritability.
>
> Serotonin + Norepinephrine + Dopamine: Involved in: mood, emotion, and cognitive function.
>
> As for the pharmacology of Kava Kava, I have no idea. I have never seen serotonin syndrome result from the use of an SSRI and Kava Kava. I have seen some fairly nasty, flaking rashes result from the use of high doses of Kava Kava, over a long period of time, though.
>
> I hope that this (and the link) are of some use to you. - Cam
>
Posted by Cam W. on September 7, 2001, at 15:01:49
In reply to Re: Reductionism » Cam W., posted by Adam on September 7, 2001, at 14:55:03
Adam - I really wasn't dismissing reductionism; you are right, you wouldn't know how the car worked unless you knew what the spark plug did. I do think we are at a point in research where we must start looking at the bigger picture. In other word, we have to stop worrying about whether increasing serotonin or dopamine will alleviate depressive symptoms, and find another angle of attack. Obviously, the monominergic theory of depression is not the answer.
Thanks for your perspectives. - Cam
Posted by Adam on September 7, 2001, at 17:18:53
In reply to Re: Reductionism » Adam, posted by Cam W. on September 7, 2001, at 15:01:49
>Obviously, the monominergic theory of depression is not the answer.
Yeah, it's 1950s technology, basically. The sad thing is, for all the specificity of the new drugs, we haven't really progressed all that much from where we were back then, as far as efficacy. And nothing works as reliably as ECT, which is 1930s or earlier.
I think progress will be made when "depression" is recognized as the anachronism that it is, and the DSM-IV is a museum piece. The treatments will be as varied as the number of illnesses that have, up to the present, fallen into this wastebasket syndrome, "depression". Careful use of reductive science will point the way to differentiating these illnesses, and treating them efficiently.
>
> Thanks for your perspectives. - Cam
Posted by Tony P on September 7, 2001, at 22:12:52
In reply to Re: Cam, could you please explain me something? » Cam W., posted by mgrueni on September 7, 2001, at 13:24:21
I have used kava extensively (myself) along with Serzone for a year or so, and more recently with Wellbutrin. I know neither of these work the same as the standard SSRI's, but my experience with these two AD's is that there wasn't even a hint of anything I could identify as a serotonin excess effect - unless feeling extra cheerful and chatty counts!
With Wellbutrin the kava seems somewhat less effective - but I am feeling so good on the WB that I no longer feel the need for the extra boost, so that's OK.
I can also vouch for the skin problem. For me, just dry skin progressing to flaking almost like a mild sunburn. That's only at quite high doses, though, say more than 6,000 mg of 30% standardized extract per day - that would be 20 extra-strength caps - YMMV of course.
Tony P
[snipped]
>
> < As for the pharmacology of Kava Kava, I have no idea. I have never seen serotonin syndrome result from the use of an SSRI and Kava Kava. I have seen some fairly nasty, flaking rashes result from the use of high doses of Kava Kava, over a long period of time, though. >
>
> Yes? Rashes? That`s news to me.
> But, I think I will not recommend Kava Kava in combination with Effexor, as long as there are no new reasearches which say that it definitely isn`t dangerous - better too careful than too experimental. It seems, valerian is working quite good on my friend, so I hope that will solve the problem.
>
>
> < I hope that this (and the link) are of some use to you. - Cam >
>
> Yes, thank you :o)
>
> Micha
>
Posted by Cruz on September 10, 2001, at 1:29:49
In reply to Re: Cam, could you please explain me something?, posted by Cam W. on September 7, 2001, at 9:53:39
People seem to be stuck in the box of thinking the brain is all that constitutes the mind. Your entire body has a role in how your mind functions.
I have a imbalance in my endocrine system which alters my circadian rythmn, causing problems with my mind. My symptoms are like many with atypical depression. But is it depression? When someone is eventually diagnosed with an underactive thyriod, they are diagnosed with Hypothyriod and treated accordingly. I've seen many cases like this when they had previously been diagnosed with depression and treated with AD's. We and researchers need to get out of the box of nuerotransmitter theories and look at the big picture. It never ceases to amaze me, how narrow many persons vision can be.
> Micha - For years, scientists have been breaking the brain down into smaller and smaller parts to see how it works (reductionism). Now that they have got down to neurotransmitters, second messenger systems, and especially gene transcription.
>
> I like to use the "automobile as human body" analogy. It he brain were the engine, then when we get down to the neurotransmitter level, we can equate (say) serotonin to spark plugs of the electrical system. Now, an isolated spark plug does not do much; it does not tell us how the car runs. We have to step back from the spark plug to see how it works in relation to the rest of parts it attaches to (and also what those other parts attach to).
>
> Of course, the brain is a much more complex piece of machinery than a car, and the analogy is far from perfect; but I hope you can see what I am trying to say. As for the functions of serotonin and norepinephrine, I will give an oversimplified answer of their effects. A far more in depth explanation can be found at the following website:
>
> http://www.acnp.org/g4/4thgen.php
>
> Serotonin: Involved in: sleep initiation, impulsivity, mood modulation, pain modulation, modulation of aggression, control of anxiety, maintenance of alertness.
>
> Norepinephrine: Involved in: sleep maintenance, mood modulation, energy, interest, vigilance, self-perception.
>
> Serotonin + Norepinephrine: Involved in: anxiety and irritability.
>
> Serotonin + Norepinephrine + Dopamine: Involved in: mood, emotion, and cognitive function.
>
> As for the pharmacology of Kava Kava, I have no idea. I have never seen serotonin syndrome result from the use of an SSRI and Kava Kava. I have seen some fairly nasty, flaking rashes result from the use of high doses of Kava Kava, over a long period of time, though.
>
> I hope that this (and the link) are of some use to you. - Cam
>
Posted by Elizabeth on September 12, 2001, at 3:15:03
In reply to Cam, could you please explain me something?, posted by mgrueni on September 7, 2001, at 5:46:18
> I am a pharmacist assistant, so I do know the basics about how antidepressants work.
Hi there. I think that most people who post to this board have a basic understanding of the pharmacodynamics of ADs, or if not, they develop such an understanding quickly after they start reading!
> I am asking for a particular reason. One of my friends is taking Effexor XR (150mg/day) and has massive sleep disorder (*broken* sleep plus waking up at 5:00 am and couldn`t get back to sleep again)
> Now I wonder, whether Effexor could be the cause of this problems (or at least increasing them, as he had this problems before, but they got worse under Effexor)Effexor can certainly cause frequent awakenings. Like the SSRIs, it causes a number of peculiar effects on sleep architecture and is often associated with exacerbation of insomnia.
A common solution is to add a sedating drug at bedtime. Some such drugs are: low-dose Remeron (7.5-15 mg, usually), trazodone (usually starting at 50 mg), benzodiazepines (e.g., Klonopin 1-2 mg), Ambien (about 10 mg), an antihisamine (such as Benadryl or Atarax, about 25-50 mg), a tricyclic antidepressant (e.g., doxepin or amitriptyline, about 25-50 mg I think), or clonidine (about 0.1 mg). If none of these provides relief without intolerable side effects, a more extreme measure would be to use an atypical antipsychotic drug in a low dose: for example, Zyprexa 5 mg or Seroquel 50 mg.
> * what exactly does Serotonine do (physical and psychological effects)
This is a *very* complicated question. Serotonin seems to regulate certain biorhythms, though, such as the circadian cycle. It is also involved in emotional regulation, with negative associations to agitated dysphoric states. Chronic use of serotonergic drugs can lead to an "apathy syndrome" that has been described in some places. Some anxious people appear to be hypersensitive to serotonin.
> * what effects does noradrenaline has on one`s psyche?
Another complicated one. It is generally associated with alertness and energy.
> And, what do you think about Kava-Kava to help his sleep disorder?
I'm not well-versed about this one, but I believe it enhances GABA-A binding. It can have dangerous interactions with benzodiazepines. The serotonin syndrome is not an issue as far as I'm aware, but the herb may have some noradrenergic activity. I can find no citations in the literature regarding which enzymes are involved in its metabolism.
It's thought to be a reversible MAO-B inhibitor; this should not cause any interactions with serotonergic drugs.
-elizabeth
Posted by Tony P on September 13, 2001, at 1:21:14
In reply to Re: Effexor and sleep » mgrueni, posted by Elizabeth on September 12, 2001, at 3:15:03
[snip]
> > And, what do you think about Kava-Kava to help his sleep disorder?
>
> I'm not well-versed about this one, but I believe it enhances GABA-A binding. It can have dangerous interactions with benzodiazepines. The serotonin syndrome is not an issue as far as I'm aware, but the herb may have some noradrenergic activity. I can find no citations in the literature regarding which enzymes are involved in its metabolism.
>
> It's thought to be a reversible MAO-B inhibitor; this should not cause any interactions with serotonergic drugs.
>
> -elizabethI've found Kava to be safe personally with Serzone (not an SSRI but certainly serotonergic). See my post a couple of weeks ago (archived now) re taking the standardized powder with hot choc. mix for best absorption. Watch out for overstimulation taking Kava at bedtime, though - it seems to have an initial stimulant and disinhibiting effect for an hour or two, then the relaxation kicks in.
Oddly, Wellbutrin seems to dull the Kava's stimulant effect on me - it's almost like I'm feeling so good on the WB, why bother trying to feel better??
Tony
This is the end of the thread.
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