![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 17 of 17. This is the beginning of the thread.
Posted by PaulB on November 29, 2001, at 22:32:57
There seems to be no doubt that Nardil and Parnate are more effective for treating social phobia than all the SSRI's yet I do not understand why. The SSRI's, particularly Sertraline and Paroxetine are highly selective and therefore target the 5-HT subtypes that regulate anxiety and depression. On the other hand the MAOI's are not selective in that they inhibit the breakdown of all subtypes of serotonin. So I am puzzzled as to why Nardil is the 'gold standard' for SP. Of course one argument would be that Nardil has some gabergic properties but even the newer reversible MAOI's such as Moclobemide, at high doses are particularly effective for treating social phobia, and do not possess any gabergic properties. My suggestion would be that 'maybe'inhibition of the MAOI enzyme is a more potent anti-depressant mechanism than re-uptake of neurotransmitters? I dont know? Given that there is such a great margin between the effectiveness of Nardil compared to Paroxetine and the other 5HT re-uptakers there must be some obvious reason because Nardil's effectiveness is significant. I would like to read some educated reasons as to why this may be.
Thanks in advance for any responses.
Posted by pat c. on November 29, 2001, at 23:16:46
In reply to Why Is Nardil superior to SSRIs for SP, posted by PaulB on November 29, 2001, at 22:32:57
When Nardil is metabolized, the metabolized product increases GABA.
Try Klonopin. It does the same thing, except it in Klonopin's case, it makes the GABA receptors more receptive, rather than increasing the absolute level of GABA.
Neurontin is good too.
I haven't had any luck with SSRIs for
social phobia.Just Nardil and klonopin, and I prefer klonopin, due to Nardil's side effects.
If you have atypical depression, then Nardil would be the most effective drug.
Also, try not to drink too much alcohol, if at all.
Pat
Posted by Elizabeth on November 30, 2001, at 2:21:54
In reply to Why Is Nardil superior to SSRIs for SP, posted by PaulB on November 29, 2001, at 22:32:57
I think you might have a mistaken idea of what "selective" in "selective serotonin reuptake inhibitor" means. There's only one "type of serotonin." SSRIs increase the amount of serotonin available outside of neurons; serotonin is an agonist at all types of serotonin *receptors* (there were 14 known serotonin receptor subtypes, last I checked).
SSRIs are "selective" in that they don't inhibit the reuptake of other monoamines (much) at prescribed doses. (Dopamine is an example of another monoamine besides serotonin.) They also selectively block the serotonin transporter (the reuptake site) without much (direct) effect on other receptor types (for example, they don't block type 2c serotonin receptors, they don't activate histamine receptors, etc.).
Monoamine oxidase inhibitors, in contrast, increase the amount of monoamines available -- in the brain and elsewhere. (MAO is found all over the body, really; it's kind of amazing how few side effects they have, considering how widespread their effect is.) This means all monoamines, not just serotonin.
The available MAOIs also have other effects. Phenelzine, for example, increases the amount of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the brain. (To give you an idea of what GABA might have to do with anxiety, consider that benzodiazepines such as Valium, Ativan, Xanax, etc., work by increasing the effectiveness of GABA.) Parnate is thought to have some amphetamine-like (stimulant) effects, although nobody ever bothered to find out what these effects might be (it's an old drug, off patent, and there's little interest in studying it, although there is a lot we could learn).
None of this really explains why Nardil or Parnate might be better for social phobia than the SSRIs; practically, it just seems that they are. (This is because nobody really knows the cause of social phobia (or any other psych disorder) on a biomolecular level.) Nardil has been more extensively tested, and because of its effect on GABA concentrations there's reason to believe it might be more effective, than Parnate for anxiety disorders (although Parnate is known to work for SP also, they've never been tested against each other).
Moclobemide, incidentally, probably isn't any better than the SSRIs for social phobia (or, for that matter, depression). Moclobemide is a reversible (competitive) MAOI, meaning that it displaces other substrates, but doesn't effectively destroy the enzyme the way that Nardil, Parnate, Marplan, Marsilid, etc. do.
-elizabeth
Posted by PaulB on November 30, 2001, at 12:36:54
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on November 30, 2001, at 2:21:54
You know SSRI's exert their antidepressant effect differently to MAOIs. For whatever reason inhibition of the MAOI enzyme may just be a more effective mechanism to help control social anxiety. MAOI antidepressants in general may be more potent antidepressants for they are prescribed when other antidepressants do not work or people have relapsed on them.
The reason I would prefer to take a SSRI than a MAOI is because of their selectivity which allows them to work for longer. I have recurrant bouts of depression and with Paroxetine I found that the effect lasted much longer than Venlafaxine which is not selective.
Posted by Elizabeth on November 30, 2001, at 15:37:45
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on November 30, 2001, at 12:36:54
> You know SSRI's exert their antidepressant effect differently to MAOIs.
Yes. The two classes of drugs both increase the amount of serotonin available, but they do so by different mechanisms, and MAOIs have other effects too (because the enzyme, MAO, metabolizes other neurotransmitters besides serotonin). Inhibition of MAO probably increases serotonin concentrations to a greater degree than serotonin reuptake blockade does: metabolism of serotonin by MAO accounts for a lot more of the "cleanup" of stray serotonin than does reuptake into cells.
> MAOI antidepressants in general may be more potent antidepressants for they are prescribed when other antidepressants do not work or people have relapsed on them.
That's right, although it's a misuse of the word "potent." "Potency" just refers to the amount of a drug needed to achieve a particular effect -- thus we could say that Parnate is a slightly more potent MAO inhibitor than Nardil is (you can take a smaller dose of Parnate and achieve the same percent MAO inhibition, although the dose difference is small), or that Prozac, Paxil, and Celexa are more potent serotonin reuptake inhibitors than Zoloft and Luvox are (the first three drugs are generally clinically effective in doses ranging from 20-80 mg or so, while the effective daily dose of Zoloft will be more like 50-200 mg and most people who take Luvox need 100-300 mg/day). But saying that Parnate is a more potent antidepressant than Prozac is really doesn't make sense since they don't do the same thing.
> The reason I would prefer to take a SSRI than a MAOI is because of their selectivity which allows them to work for longer.
Allows them to work for longer? I'm not sure how you came to this conclusion. ???
> I have recurrant bouts of depression and with Paroxetine I found that the effect lasted much longer than Venlafaxine which is not selective.
There are a lot of things we don't understand about these drugs (that's what makes them so interesting, IMO), but your experience probably did not have anything to do with the selectivity of Paxil. (You're right that while Paxil is a selective serotonin reuptake inhibitor, Effexor is a nonselective monoamine reuptake inhibitor, blocking the uptake of serotonin, norepinephrine, and (at very high doses) dopamine.)
-elizabeth
Posted by manowar on November 30, 2001, at 16:25:18
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on November 30, 2001, at 15:37:45
>(You're right that while Paxil is a selective serotonin reuptake inhibitor, Effexor is a nonselective monoamine reuptake inhibitor, blocking the uptake of serotonin, norepinephrine, and (at very high doses) dopamine.)
>
> -elizabeth
Effexor is a MAOI?I'm interested in the possibility in trying a MAOI. Last year I asked my pdoc and he said he would never consider it. He said that even if the "cheese effect" did not exist that his experience in the past (he's quite old) is that it didn't work often, and when it did-- only with women. I thought he was full of ----. Since you have a lot of experience with MAOI's is there any substance to his claim? Should a MAOI be my next "drug of choice"?
Posted by PaulB on November 30, 2001, at 19:11:53
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on November 30, 2001, at 15:37:45
> > You know SSRI's exert their antidepressant effect differently to MAOIs.
>
> Yes. The two classes of drugs both increase the amount of serotonin available, but they do so by different mechanisms, and MAOIs have other effects too (because the enzyme, MAO, metabolizes other neurotransmitters besides serotonin). Inhibition of MAO probably increases serotonin concentrations to a greater degree than serotonin reuptake blockade does: metabolism of serotonin by MAO accounts for a lot more of the "cleanup" of stray serotonin than does reuptake into cells.
>
>THATS A GREAT THEORY AND YOU MAY BE RIGHT
>
>MAOI antidepressants in general may be more potent antidepressants for they are prescribed when other antidepressants do not work or people have relapsed on them.
>
> That's right, although it's a misuse of the word "potent." "Potency" just refers to the amount of a drug needed to achieve a particular effect -- thus we could say that Parnate is a slightly more potent MAO inhibitor than Nardil is (you can take a smaller dose of Parnate and achieve the same percent MAO inhibition, although the dose difference is small), or that Prozac, Paxil, and Celexa are more potent serotonin reuptake inhibitors than Zoloft and Luvox are (the first three drugs are generally clinically effective in doses ranging from 20-80 mg or so, while the effective daily dose of Zoloft will be more like 50-200 mg and most people who take Luvox need 100-300 mg/day). But saying that Parnate is a more potent antidepressant than Prozac is really doesn't make sense since they don't do the same thing.
>
>LET ME GET THIS STRAIGHT. YOUR NOT SAYING FLUOXETINE IS MORE POWERFUL THAN SERTRALINE ALTHOUGH I AGREE SERTRALINE COMPETES WITH CELEXA AND PAXIL. I MAY HAVE MISUNDERSTOOD YOU HERE.
>
The reason I would prefer to take a SSRI than a MAOI is because of their selectivity which allows them to work for longer.
>
Allows them to work for longer? I'm not sure how you came to this conclusion.???
>
I TRIED TO EXPLAIN IT BUT COULDNT. WE CAN AGREE TO DIFFER AND THATS OKAY. I WOULD ADD THAT VENLAFAXINE WORKED FOR TWO WEEKS AND PAROXETINE WORKED FOR SEVEN MONTHS SO????.
>
I have recurrant bouts of depression and with Paroxetine I found that the effect lasted much longer than Venlafaxine which is not selective.
>
> There are a lot of things we don't understand about these drugs (that's what makes them so interesting, IMO), but your experience probably did not have anything to do with the selectivity of Paxil. (You're right that while Paxil is a selective serotonin reuptake inhibitor, Effexor is a nonselective monoamine reuptake inhibitor, blocking the uptake of serotonin, norepinephrine, and (at very high doses) dopamine.)YES, YOU KNOW EXPERTS SAY WE THINK THAT THESE PILLS WORK BY INCREASING SEROTONIN, NOREPINEPHRINE AND DOPAMINE BUT WE CANNOT SAY FOR SURE ALTHOUGH I THINK WE ALL KNOW THAT THERE IS MONOAMINE INCREASE THAT EXERTS THE ANTIDEPRESSANT EFFECT.
NICE TO HEAR FROM YOU
PaulB
Posted by Elizabeth on December 1, 2001, at 13:25:21
In reply to MAOIs » Elizabeth, posted by manowar on November 30, 2001, at 16:25:18
> > (You're right that while Paxil is a selective serotonin reuptake inhibitor, Effexor is a nonselective monoamine reuptake inhibitor, blocking the uptake of serotonin, norepinephrine, and (at very high doses) dopamine.)
>
> Effexor is a MAOI?I don't believe that anyone said that. (No, it's not. As I said in the above quote, it's a monoamine reuptake inhibitor.)
> I'm interested in the possibility in trying a MAOI. Last year I asked my pdoc and he said he would never consider it. He said that even if the "cheese effect" did not exist that his experience in the past (he's quite old) is that it didn't work often, and when it did-- only with women.
If I were in your situation, I would ask to see some numbers. I have a hunch that his prejudice against MAOIs (and yes, this prejudice is unfounded) is influencing his impression of how well they work. It also may be that his fears are preventing him from using effective doses of MAOIs. On the other hand, it seems that he's not very well educated about the risk of food interactions -- it sounds like he thinks it is something very common and unpredictable -- so maybe he doesn't feel qualified to prescribe MAOIs, and if so he might be right.
It may be that women are less likely to respond to tricyclics and so are more likely to end up being given MAOIs (since most pdocs still believe that TCAs should be tried before MAOIs). That doesn't mean that MAOIs work poorly for men, though.
> Should a MAOI be my next "drug of choice"?
I don't have an opinion about that...I know we spoke before, but I don't recall much about the specifics of your situation. If you're having trouble finding something that works for you among the newer ADs, and if your pdoc has this kind of attitude toward the older ones, it might be time to think about looking for a more informed pdoc. Don't take this as gospel, of course, it's just a thought based on what you have said here.
In general, I think it is worthwhile for people with a wide range of different types of depression and anxiety disorders to try MAOIs if the newer classes of ADs don't work. I don't think that TCAs should necessarily be tried before MAOIs.
-elizabeth
Posted by Elizabeth on December 1, 2001, at 14:11:59
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on November 30, 2001, at 19:11:53
> > Inhibition of MAO probably increases serotonin concentrations to a greater degree than serotonin reuptake blockade does: metabolism of serotonin by MAO accounts for a lot more of the "cleanup" of stray serotonin than does reuptake into cells.
> >
> THATS A GREAT THEORY AND YOU MAY BE RIGHTI think it's more than just a theory: I bet that if we did some research, we could uncover plenty of evidence showing that quite a bit more serotonin is eliminated by metabolism (via MAO) than by reuptake. In any case, there are many reasons to suppose that this is true.
> LET ME GET THIS STRAIGHT. YOUR NOT SAYING FLUOXETINE IS MORE POWERFUL THAN SERTRALINE ALTHOUGH I AGREE SERTRALINE COMPETES WITH CELEXA AND PAXIL. I MAY HAVE MISUNDERSTOOD YOU HERE.
That might be. Try reading it again -- I hope I wasn't too unclear. If there's something there that didn't make sense, please let me know and I will try to clarify it.
The point of what I was trying to say is that "potent" has a specific meaning, and it does not mean the same thing as "effective" or "strong." Saying that Prozac is more "potent" than Zoloft doesn't mean that Prozac is a stronger AD or that it works better than Zoloft; it just means that Prozac works at much smaller *doses*. (A person who feels well on 20 mg of Prozac would probably feel no effect at all from 20 mg of Zoloft, for example, but 50 or 75 mg of Zoloft might work just as well as the 20 mg of Prozac for that person.)
> > > The reason I would prefer to take a SSRI than a MAOI is because of their selectivity which allows them to work for longer.
> >
> Allows them to work for longer? I'm not sure how you came to this conclusion.???
> >
> I TRIED TO EXPLAIN IT BUT COULDNT. WE CAN AGREE TO DIFFER AND THATS OKAY. I WOULD ADD THAT VENLAFAXINE WORKED FOR TWO WEEKS AND PAROXETINE WORKED FOR SEVEN MONTHS SO????.Okay, if I read you right, it sounds like you're saying that you concluded that Paxil's selectivity made its effects last longer than those of Effexor. (Please let me know if I've got it wrong -- I want to help.) There are a couple of problems with this reasoning.
First of all, you can't generalize what happened to you and assume that it says something about what the drug usually does. People have an amazing variety of responses to these drugs, for reasons that we just don't understand yet. So, what happened to you may have nothing to do with what happens for most people. And indeed, your particular situation is not a common one; it's specific to you, and while there is probably someone out there who had a similar experience, it's certainly not the usual result of trying Paxil and Effexor separately. There probably is no "usual result" -- people's response patterns vary so much.
Second, you can't draw the conclusion that the selectivity difference is what made Paxil work for a while while Effexor only seemed to work for two weeks. There are differences between these drugs that we don't know about. For whatever reason, it's possible that Paxil just works better for you than Effexor does.
Also, since Paxil worked for such a brief time (a few months really isn't that long), it's possible that what you were experiencing was a temporary lift in your mood, and not a true drug response. This is actually pretty common. Depression and other long-lasting conditions often get better temporarily (for a few days, a few weeks, or even a few months), and the hope that comes with a new medication can also cause your mood to lift for a while.
The same principle applies to the Effexor, even more so since you said the Effexor worked for only two weeks. Two weeks really isn't long enough to know if an AD is working at all. If you were feeling better in the first two weeks that you were taking Effexor, it probably wasn't due to the Effexor -- it probably was a coincidence. It's likely that what you had was not a true drug response, but a temporary improvement, which may have been contributed to by your and your doctor's hope that the new medicine would work. But again, this doesn't mean that the improvement was a response to the medication.
So, my guess is that, for whatever reason, Effexor didn't work for you. The Paxil may have worked and "pooped out" after a brief time, or it may not have been working at all, either. But again, we don't know *why* this would be, and we don't have any reason to believe that selectivity would cause drugs to work longer. (SSRIs do poop out quite often. So do other types of ADs. There's no evidence that it is less likely to happen with SSRIs.)
> I have recurrant bouts of depression and with Paroxetine I found that the effect lasted much longer than Venlafaxine which is not selective.
Right, but as I've explained, that doesn't mean that selectivity is the reason that Paxil worked longer (or -- and this seems more likely -- that Paxil worked and Effexor did not). Sometimes people don't respond to one SSRI but a different SSRI will work; we don't know why this is, but it is true.
I'd be interested to know what dose of Effexor you were taking and how long you took it, if you can recall.
> YES, YOU KNOW EXPERTS SAY WE THINK THAT THESE PILLS WORK BY INCREASING SEROTONIN, NOREPINEPHRINE AND DOPAMINE BUT WE CANNOT SAY FOR SURE ALTHOUGH I THINK WE ALL KNOW THAT THERE IS MONOAMINE INCREASE THAT EXERTS THE ANTIDEPRESSANT EFFECT.
Well, the monoamine increase causes a cascade of other things to happen. I think researchers believe that it is one (or more) of these indirect effects that causes the relief from depression. One thing that we do know is that the old "monoamine hypothesis" of depression is not the correct explanation -- it used to be thought that depression was caused by inadequate amounts of monoamines, but we now know it's more complicated. How much more complicated, and what the real answer is, nobody knows.
-elizabeth
p.s. Typing in all-caps is usually considered to mean that you're "shouting." I know that's not what you meant by it, but in the future, it'd probably be a good idea to avoid all-caps, so as to prevent misunderstandings.
Posted by PaulB on December 2, 2001, at 14:03:07
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on December 1, 2001, at 14:11:59
> > > Inhibition of MAO probably increases serotonin concentrations to a greater degree than serotonin reuptake blockade does: metabolism of serotonin by MAO accounts for a lot more of the "cleanup" of stray serotonin than does reuptake into cells.
> > >
> > Thats a great theory and you may be right
>
> I think it's more than just a theory: I bet that if we did some research, we could uncover plenty of evidence showing that quite a bit more serotonin is eliminated by metabolism (via MAO) than by reuptake. In any case, there are many reasons to suppose that this is true.
>
> > Let me get this straight. Your not saying Fluoxetine is more powerful than Sertraline although I agree Sertraline competetes with Celexa and Paxil. I may have misunderstood you here.
>
> That might be. Try reading it again -- I hope I wasn't too unclear. If there's something there that didn't make sense, please let me know and I will try to clarify it.
>
> The point of what I was trying to say is that "potent" has a specific meaning, and it does not mean the same thing as "effective" or "strong." Saying that Prozac is more "potent" than Zoloft doesn't mean that Prozac is a stronger AD or that it works better than Zoloft; it just means that Prozac works at much smaller *doses*. (A person who feels well on 20 mg of Prozac would probably feel no effect at all from 20 mg of Zoloft, for example, but 50 or 75 mg of Zoloft might work just as well as the 20 mg of Prozac for that person.)>I understand. At the therapeutic dose Sertraline would block the serotonin re-uptake pump more powerfully than Prozac at its theraputic dose but not at Prozacs therapeutic dose.
> > > > The reason I would prefer to take a SSRI than a MAOI is because of their selectivity which allows them to work for longer.
> > >
> > Allows them to work for longer? I'm not sure how you came to this conclusion.???
> > >
> > I tried to explain but couldnt. We can agree to differ and thats okay. I would add that Venlafaxine worked for two weeks and paroxetine worked for seven months so????.
>
> Okay, if I read you right, it sounds like you're saying that you concluded that Paxil's selectivity made its effects last longer than those of Effexor. (Please let me know if I've got it wrong -- I want to help.) There are a couple of problems with this reasoning.
>
> First of all, you can't generalize what happened to you and assume that it says something about what the drug usually does. People have an amazing variety of responses to these drugs, for reasons that we just don't understand yet. So, what happened to you may have nothing to do with what happens for most people. And indeed, your particular situation is not a common one; it's specific to you, and while there is probably someone out there who had a similar experience, it's certainly not the usual result of trying Paxil and Effexor separately. There probably is no "usual result" -- people's response patterns vary so much.
>
> Second, you can't draw the conclusion that the selectivity difference is what made Paxil work for a while while Effexor only seemed to work for two weeks. There are differences between these drugs that we don't know about. For whatever reason, it's possible that Paxil just works better for you than Effexor does.>
> Also, since Paxil worked for such a brief time (a few months really isn't that long), it's possible that what you were experiencing was a temporary lift in your mood, and not a true drug response. This is actually pretty common. Depression and other long-lasting conditions often get better temporarily (for a few days, a few weeks, or even a few months), and the hope that comes with a new medication can also cause your mood to lift for a while.
>
> The same principle applies to the Effexor, even more so since you said the Effexor worked for only two weeks. Two weeks really isn't long enough to know if an AD is working at all. If you were feeling better in the first two weeks that you were taking Effexor, it probably wasn't due to the Effexor -- it probably was a coincidence. It's likely that what you had was not a true drug response, but a temporary improvement, which may have been contributed to by your and your doctor's hope that the new medicine would work. But again, this doesn't mean that the improvement was a response to the medication.
>
> So, my guess is that, for whatever reason, Effexor didn't work for you. The Paxil may have worked and "pooped out" after a brief time, or it may not have been working at all, either. But again, we don't know *why* this would be, and we don't have any reason to believe that selectivity would cause drugs to work longer. (SSRIs do poop out quite often. So do other types of ADs. There's no evidence that it is less likely to happen with SSRIs.)>I believe, in my case that if there is little serotonin in the brain causing depression, anxiety and its various subtypes then blocking the re-uptake pump of just a few serotonin pumps will allow what little serotonin there is to circulate for longer at those few sites. With the SSRI's this is usually 5-HT1a, 5-HT2a and c and 5-HT3. I dont think Venlafaxine has that advantage because it is an SRI. To understand the adavnatage of the SSRIs as apposed to the SRI Venlafaxine you need only to look at their names.
> > I have recurrant bouts of depression and with Paroxetine I found that the effect lasted much longer than Venlafaxine which is not selective.
>
> Right, but as I've explained, that doesn't mean that selectivity is the reason that Paxil worked longer (or -- and this seems more likely -- that Paxil worked and Effexor did not). Sometimes people don't respond to one SSRI but a different SSRI will work; we don't know why this is, but it is true.> Okay
> I'd be interested to know what dose of Effexor you were taking and how long you took it, if you can recall.
> I was prescribed 75mg of the slow-release form of Effexor once a day in November 1999. I noticed a benefit after two weeks and this lasted for about 2 weeks before 'poop-out'. My physician did not think an increase in dosage would be beneficial. In April of that year I was prescribed Paxil(Seroxat over here) and the antidepressant/anxiety effect lasted for six months.
> > Yes you know experts say we think that these pills work by increasing norepinephrine and dopamine but we cannot say for sure although I think we all know that there is a monoamine increase that exerts the antidepressant effect.
>
> Well, the monoamine increase causes a cascade of other things to happen. I think researchers believe that it is one (or more) of these indirect effects that causes the relief from depression. One thing that we do know is that the old "monoamine hypothesis" of depression is not the correct explanation -- it used to be thought that depression was caused by inadequate amounts of monoamines, but we now know it's more complicated. How much more complicated, and what the real answer is, nobody knows.I agree. There is now much focus on substance p and its relationship with depression. The discovery of the first substance P antagonist (Cp-96,345) was made by scientists at pfizer. they have used this as a starting point to develop a series of compounds, with improved selectivity and potency and which block the activation of nerves in the locus ceruleus-one of the areas involved in mood regulation. There are also hormone based approaches being developed. Medicines that modify the hormonal changes that underlie depression. Disturbances in the HPA axis are common in depression.
>
> >I would add that the newer MAOI's can be effective as the older 'irreversible' MAOIs if they are prescibed in very high doses.http://members.tripod.com/~cyberpsy/JWGTiller.htm
Also you could go to mhsource.com site and look up an article entitled 'the Canadian Experience with RIMAs by Russell T.Joffe, MD, Psychiatric Times , June 1996, Vol X111 Issues 6> -elizabeth
>
> p.s. Typing in all-caps is usually considered to mean that you're "shouting." I know that's not what you meant by it, but in the future, it'd probably be a good idea to avoid all-caps, so as to prevent misunderstandings.
Posted by Elizabeth on December 2, 2001, at 17:04:00
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on December 2, 2001, at 14:03:07
> I understand. At the therapeutic dose Sertraline would block the serotonin re-uptake pump more powerfully than Prozac at its theraputic dose but not at Prozacs therapeutic dose.
I don't know that Zoloft is "more powerful" *or* "less powerful" a serotonin reuptake inhibitor than Prozac is, and that's certainly not what I was saying. They just have different equivalent doses.
> I believe, in my case that if there is little serotonin in the brain causing depression, anxiety and its various subtypes then blocking the re-uptake pump of just a few serotonin pumps will allow what little serotonin there is to circulate for longer at those few sites.
Oh dear, I seem to have confused you again. I'm sorry.
Okay, first of all, when you block serotonin reuptake, you block *all* the reuptake sites (transporters, pumps), not just some of them. This results in increased amounts of serotonin, because the serotonin is not being taken back up into the cells. (Remember: there's only *one* type of serotonin, although there are many types of receptors which the serotonin can interact with or "bind to.")
Serotonin receptors (not the same thing as the transporter or reuptake site) are *not* blocked by the SSRIs, although certain subtypes are blocked by non-SSRI antidepressants like Serzone (blocks certain 5-HT2 receptors) and Remeron (blocks 5-HT2 (not sure which subtypes) and -3 receptors).
Last, of course, it's pretty clear that the cause of depression (and anxiety) is not anything as simple as "too little serotonin." The extra serotonin is just the first step in a chain reaction which, ultimately, can relieve depression.
> With the SSRI's this is usually 5-HT1a, 5-HT2a and c and 5-HT3.
No; SSRIs do not affect a specific type of serotonin receptor.
> I was prescribed 75mg of the slow-release form of Effexor once a day in November 1999.
Okay. An interesting thing about Effexor is that it has some effects that aren't significant until you reach a certain dose. At 75 mg/day, it was probably acting as an SSRI. At higher doses, it starts blocking norepinephrine reuptake, and at still higher doses, it is a dopamine reuptake blocker too.
> I noticed a benefit after two weeks and this lasted for about 2 weeks before 'poop-out'. My physician did not think an increase in dosage would be beneficial.
That's peculiar, because it is known that Effexor can become more effective as you increase the dose, and 75 mg/day is not a very high dose (it's at the low end of the effective range). The maximum recommended dose is 375 mg, and some people go higher than that. So you weren't taking very much and possibly *could* have improved if you had taken more. Also, I think it is very possible that your brief improvement may not have been a drug response, but just a spontaneous temporary improvement.
> There is now much focus on substance p and its relationship with depression. The discovery of the first substance P antagonist (Cp-96,345) was made by scientists at pfizer.
It's not the first substance P antagonist to be studied for depression, but it still might prove to be useful. There are other approaches being tried as well, as you know. But just as a response to an SSRI does not mean that somebody's depression was caused by "too little serotonin," it's also true that a person who responds to a substance P receptor blocker (if these prove effective) does not necessarily have depression that is caused by neuropeptide deficiencies. And while the hypothalamic-pituitary-adrenal dysregulation in depression has been recognized for a long time, it's understood that this is not necessarily the cause of the depression.
> > >I would add that the newer MAOI's can be effective as the older 'irreversible' MAOIs if they are prescibed in very high doses.
> http://members.tripod.com/~cyberpsy/JWGTiller.htmThey work for some people with treatment-resistant depression (which is the special niche of the irreversible MAOIs), but moclobemide, at least, has a bad reputation -- it tends to be poorly tolerated, it often doesn't work, and when it does work it often loses effect.
BTW, 900 mg/day (the dose cited in the article you referred me to) is not especially high (many doctors go over the "recommended maximum") and I've known plenty of people who have taken higher doses. But at 900 mg/day or more, moclobemide often causes intolerable side effects. Agitation and insomnia seem to be paricularly common.
> Also you could go to mhsource.com site and look up an article entitled 'the Canadian Experience with RIMAs by Russell T.Joffe, MD, Psychiatric Times , June 1996, Vol X111 Issues 6
I think the title there is a bit misleading; perhaps "One Canadian Doctor's Experience with RIMAs" would be more appropriate.
RIMAs work well enough as a first-line therapy, and indeed, they are one (along with the SSRIs) in many countries, but their reputation is that they are not especially helpful for people who have treatment-resistant depression (i.e., people for whom a lot of other things have failed). Moclobemide is not an appropriate substitute for Nardil or Parnate, which are mainly used in treatment-resistant depression and anxiety, and it shouldn't be considered one.
-elizabeth
Posted by PaulB on December 2, 2001, at 23:26:28
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on December 2, 2001, at 17:04:00
I sense that we are getting our wires crossed on certain issues but its been an interesting discussion. I cut the previous stuff because I wanted to open up a new discussion but still continues on the theme of MAOIS vs SSRI's
First of all I would agree that Moclobemide does not hold a good rep as being a powerful antidepressant. You really seem to know your stuff so I would like your opinion on my current drug-line up.
Sertraline 200mg/day
SAM-E 200mg/day/empty stomach
Lorazepam-PRN and when Sertraline 'poops-out' I come off Sertraline, load on 5-HTP and use Lorazepam until the Sertraline 'kicks-in' again.What do you think of this combination for serious social phobia, serious depression/anger, moderate obsessive compulsive disorder and generalised anxiety disorder?
This may not always be my combination therapy because there is clear evidence that the MAOI's are better for social phobia(my biggy)than the SSRI's. The problem is that the MAOI's are not selective and I believe that is a disadvantage. From your previous posts I sense you may not agree. Have you heard of augmeting Nardil; perhaps with an atypical antipsychotic or a 5-HT3 antagonist which were being investigated for social phobia a short while ago. The problem is that the MAOI's interact with many drugs so polypharmacy with them could be dangerous and potentially lethal. But what a weapon against social phobia a selective MAOI would be, dont you think?
Posted by Elizabeth on December 3, 2001, at 1:22:17
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on December 2, 2001, at 23:26:28
Hi Paul.
I can't say much about your combination because Zoloft is a drug that has many uses and I'm not too familiar with the over-the-counter drugs you're supplementing with (SAMe and 5-HTP).
The strategy for dealing with Zoloft poop-out is one that I have never encountered. Does it work well to keep you going? How often does the Zoloft poop out on you?
How do you think the SAMe helps you? Do you use a particular brand?
> This may not always be my combination therapy because there is clear evidence that the MAOI's are better for social phobia(my biggy)than the SSRI's.
I'm not sure there's clear evidence...but everybody seems to think so who's tried both!
> The problem is that the MAOI's are not selective and I believe that is a disadvantage.
Why would that be a problem -- why do you think that "selectivity" is necessarily a desirable thing?
As far as MAOIs go, I think that reversibility is the characteristic that makes the difference -- unfortunately, it seems to make them less powerful.
> Have you heard of augmeting Nardil; perhaps with an atypical antipsychotic or a 5-HT3 antagonist which were being investigated for social phobia a short while ago.
With atypical antipsychotics, yes (not necessarily for social phobia -- mainly for borderline personality and some kinds of depression). With 5-HT3 antagonists, no -- I don't know anybody who's found those helpful for psych disorders (except Remeron, which has so many other effects that it's hard to say whether the 5-HT3 antagonism plays much of a role).
> The problem is that the MAOI's interact with many drugs so polypharmacy with them could be dangerous and potentially lethal.
Actually, it can be done safely as long as you know what you're doing. I've combined lots of things with MAOIs, and I've always felt confident (correctly, as it turned out) that I could deal with any problem that might arise. (Furthermore, such problems were rare.) There are a few types of mechanisms that should be avoided in combination with MAOIs; as long as you know what these are and are familiar with the drugs you're taking (which you should always be, of course), you should be fine.
> But what a weapon against social phobia a selective MAOI would be, dont you think?
No. I think the RIMAs are probably about as effective as the SSRIs for social phobia, panic disorder, and depression. I don't think they have the special whatever-it-is that makes the irreversible MAOIs (Nardil especially, but also Parnate) work so well (especially for people with conditions that have otherwise been hard to treat effectively).
I am sort of interested in clorgyline -- an irreversible MAO-A inhibitor which was never marketed (AFAIK). I suspect it works about as well as the nonselective, irreversible MAOIs with about the same side effect profile.
BTW...my experience has been that the opioids work far better for social anxiety symptoms than any other drug I've tried. But my case may be complicated by Asperger's, which might make it very different from the typical case of SP. Still, I'd like to see such drugs as Ultram looked at more closely for SP -- so far, all we have to go on are case reports (albeit very enticing ones).
-elizabeth
Posted by PaulB on December 3, 2001, at 17:53:14
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on December 3, 2001, at 1:22:17
> Hi Paul.
>
> I can't say much about your combination because Zoloft is a drug that has many uses and I'm not too familiar with the over-the-counter drugs you're supplementing with (SAMe and 5-HTP).Zoloft does have many uses. It is the best antidepressant I have ever taken. It lacks the agitation and hypomania of Fluoxetine and Paroxetine. It is a calming antidepressant that just makes me feel very emotionally fit. I havent felt this good in ten years. When the effect of the Sertraline will start to wear off I will load up on 5-HTP(the precursor to serotonin)and take a course of Lorazepam until the Sertraline begins to work again. We use Lorazepam because Clonazepam(esp) and Diazepam have anticovulsant properties that may hinder the effectiveness of the antidepressant when it kicks in by lowering serotonin levels during the process of down-regulation.
>
> The strategy for dealing with Zoloft poop-out is one that I have never encountered. Does it work well to keep you going? How often does the Zoloft poop out on you?>Yes it works well to keep me going but poops out approximately every 6-7 months
>
>How do you think the SAMe helps you? Do you use a particular brand?>SAM-E enhances the synthesis of neurotranmsitters and there is significant evidence that it restores monoamine receptors. SAM-E also has the ability to improve the bodys ability to manufacture phospholipids for use in brain cells which helps with the fluidity of cell interaction. I take the Nutralife form.
>
> >This may not always be my combination therapy because there is clear evidence that the MAOI's are better for social phobia(my biggy)than the SSRI's.
>
> I'm not sure there's clear evidence...but everybody seems to think so who's tried both!
>
> > The problem is that the MAOI's are not selective and I believe that is a disadvantage.
>
> Why would that be a problem -- why do you think that "selectivity" is necessarily a desirable thing?Because as I wrote in my last post 'selectivity' allows what little serotonin there is in a depressed/anxious person to circulate for longer at certain serotonin sites i.e.5-HT2c rather than allowing the serotonin to be used up all too quickly at 5-HT1,5-HT2,5-HT3 and all its subtypes together. Read this carefully and Im sure you will understand where Im coming from but not necessarily agree. I have explained it as best as I can.
>
> As far as MAOIs go, I think that reversibility is the characteristic that makes the difference -- unfortunately, it seems to make them less powerful.
>
> > Have you heard of augmeting Nardil; perhaps with an atypical antipsychotic or a 5-HT3 antagonist which were being investigated for social phobia a short while ago.
>
> With atypical antipsychotics, yes (not necessarily for social phobia -- mainly for borderline personality and some kinds of depression). With 5-HT3 antagonists, no -- I don't know anybody who's found those helpful for psych disorders (except Remeron, which has so many other effects that it's hard to say whether the 5-HT3 antagonism plays much of a role).>So you are saying augmentation of Nardil with an atypical antipsychotic such as Zyprexa, as commonly done with Prozac could be tried.
> >The problem is that the MAOI's interact with many drugs so polypharmacy with them could be dangerous and potentially lethal.
>
> Actually, it can be done safely as long as you know what you're doing. I've combined lots of things with MAOIs, and I've always felt confident (correctly, as it turned out) that I could deal with any problem that might arise. (Furthermore, such problems were rare.) There are a few types of mechanisms that should be avoided in combination with MAOIs; as long as you know what these are and are familiar with the drugs you're taking (which you should always be, of course), you should be fine.
>
> > But what a weapon against social phobia a selective MAOI would be, dont you think?
>
> No. I think the RIMAs are probably about as effective as the SSRIs for social phobia, panic disorder, and depression. I don't think they have the special whatever-it-is that makes the irreversible MAOIs (Nardil especially, but also Parnate) work so well (especially for people with conditions that have otherwise been hard to treat effectively).>Sorry, but you misundersttood me here. I meant wouldnt a "irreversible" MAOI be a powerful weapon against social phobia if it was combined with an 5-HT antagonist. I was not referring to the newer reversible MAOIs.
> I am sort of interested in clorgyline -- an irreversible MAO-A inhibitor which was never marketed (AFAIK). I suspect it works about as well as the nonselective, irreversible MAOIs with about the same side effect profile.
>
>Well it didnt sound very promising. If people want to try Moclobemide fine but I think those articles I quoted may have been inaccurate.BTW...my experience has been that the opioids work far better for social anxiety symptoms than any other drug I've tried. But my case may be complicated by Asperger's, which might make it very different from the typical case of SP. Still, I'd like to see such drugs as Ultram looked at more closely for SP -- so far, all we have to go on are case reports (albeit very enticing ones).
I would be very grateful to hear more form you about the use of opiods for social phobia. I do not condone or approve of narcotic drugs but I do see that they have some utility for treatment-restant patients, in my opinion, and thats just my opinion. I too have Aspergers and all too frequent a symptom of Aspergers is social phobia. See my post:
http://www.dr-bob.org/babble/social/200010915/msgs/11773.html
I would like you to give me some basic information on Buprenorphine. Im sure you know a lot about it and tell me how it is different from other opioids and what may make it a useful tool for managing social phobia. I dont hold much promise for Ultram.
I am enjoying this discussion and I hope you post another responsePaulB
Posted by UK-Aspie on May 2, 2003, at 7:43:06
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on December 3, 2001, at 17:53:14
> > Hi Paul.
> >
> > I can't say much about your combination because Zoloft is a drug that has many uses and I'm not too familiar with the over-the-counter drugs you're supplementing with (SAMe and 5-HTP).
>
> Zoloft does have many uses. It is the best antidepressant I have ever taken. It lacks the agitation and hypomania of Fluoxetine and Paroxetine. It is a calming antidepressant that just makes me feel very emotionally fit. I havent felt this good in ten years. When the effect of the Sertraline will start to wear off I will load up on 5-HTP(the precursor to serotonin)and take a course of Lorazepam until the Sertraline begins to work again. We use Lorazepam because Clonazepam(esp) and Diazepam have anticovulsant properties that may hinder the effectiveness of the antidepressant when it kicks in by lowering serotonin levels during the process of down-regulation.
>
> >
> > The strategy for dealing with Zoloft poop-out is one that I have never encountered. Does it work well to keep you going? How often does the Zoloft poop out on you?
>
> >Yes it works well to keep me going but poops out approximately every 6-7 months
>
> >
> >How do you think the SAMe helps you? Do you use a particular brand?
>
> >SAM-E enhances the synthesis of neurotranmsitters and there is significant evidence that it restores monoamine receptors. SAM-E also has the ability to improve the bodys ability to manufacture phospholipids for use in brain cells which helps with the fluidity of cell interaction. I take the Nutralife form.
> >
> > >This may not always be my combination therapy because there is clear evidence that the MAOI's are better for social phobia(my biggy)than the SSRI's.
> >
> > I'm not sure there's clear evidence...but everybody seems to think so who's tried both!
> >
> > > The problem is that the MAOI's are not selective and I believe that is a disadvantage.
> >
> > Why would that be a problem -- why do you think that "selectivity" is necessarily a desirable thing?
>
> Because as I wrote in my last post 'selectivity' allows what little serotonin there is in a depressed/anxious person to circulate for longer at certain serotonin sites i.e.5-HT2c rather than allowing the serotonin to be used up all too quickly at 5-HT1,5-HT2,5-HT3 and all its subtypes together. Read this carefully and Im sure you will understand where Im coming from but not necessarily agree. I have explained it as best as I can.
> >
> > As far as MAOIs go, I think that reversibility is the characteristic that makes the difference -- unfortunately, it seems to make them less powerful.
> >
> > > Have you heard of augmeting Nardil; perhaps with an atypical antipsychotic or a 5-HT3 antagonist which were being investigated for social phobia a short while ago.
> >
> > With atypical antipsychotics, yes (not necessarily for social phobia -- mainly for borderline personality and some kinds of depression). With 5-HT3 antagonists, no -- I don't know anybody who's found those helpful for psych disorders (except Remeron, which has so many other effects that it's hard to say whether the 5-HT3 antagonism plays much of a role).
>
> >So you are saying augmentation of Nardil with an atypical antipsychotic such as Zyprexa, as commonly done with Prozac could be tried.
>
> > >The problem is that the MAOI's interact with many drugs so polypharmacy with them could be dangerous and potentially lethal.
> >
> > Actually, it can be done safely as long as you know what you're doing. I've combined lots of things with MAOIs, and I've always felt confident (correctly, as it turned out) that I could deal with any problem that might arise. (Furthermore, such problems were rare.) There are a few types of mechanisms that should be avoided in combination with MAOIs; as long as you know what these are and are familiar with the drugs you're taking (which you should always be, of course), you should be fine.
> >
> > > But what a weapon against social phobia a selective MAOI would be, dont you think?
> >
> > No. I think the RIMAs are probably about as effective as the SSRIs for social phobia, panic disorder, and depression. I don't think they have the special whatever-it-is that makes the irreversible MAOIs (Nardil especially, but also Parnate) work so well (especially for people with conditions that have otherwise been hard to treat effectively).
>
> >Sorry, but you misundersttood me here. I meant wouldnt a "irreversible" MAOI be a powerful weapon against social phobia if it was combined with an 5-HT antagonist. I was not referring to the newer reversible MAOIs.
>
> > I am sort of interested in clorgyline -- an irreversible MAO-A inhibitor which was never marketed (AFAIK). I suspect it works about as well as the nonselective, irreversible MAOIs with about the same side effect profile.
> >
> >Well it didnt sound very promising. If people want to try Moclobemide fine but I think those articles I quoted may have been inaccurate.
>
> BTW...my experience has been that the opioids work far better for social anxiety symptoms than any other drug I've tried. But my case may be complicated by Asperger's, which might make it very different from the typical case of SP. Still, I'd like to see such drugs as Ultram looked at more closely for SP -- so far, all we have to go on are case reports (albeit very enticing ones).
>
> I would be very grateful to hear more form you about the use of opiods for social phobia. I do not condone or approve of narcotic drugs but I do see that they have some utility for treatment-restant patients, in my opinion, and thats just my opinion. I too have Aspergers and all too frequent a symptom of Aspergers is social phobia. See my post:
>
> http://www.dr-bob.org/babble/social/200010915/msgs/11773.html
>
> I would like you to give me some basic information on Buprenorphine. Im sure you know a lot about it and tell me how it is different from other opioids and what may make it a useful tool for managing social phobia. I dont hold much promise for Ultram.
>
> I am enjoying this discussion and I hope you post another response
>
> PaulBI have just found this thread in a search for information relating to MAOIs and Aspergers. Looks good so far. I have been taking Venlafaxine (SSRI) with serious side effects for some years and have pressed my doctor for a change.
Very few doctors seem to be aware that Aspies often react differently from NTs to medication. I have found a site that dealt with this problem in particular, but I forgot to bookmark it and I can't find it again!
Posted by Carlos on May 4, 2003, at 16:10:29
In reply to Re: SSRIs and MAOIs for SP » PaulB, posted by Elizabeth on November 30, 2001, at 2:21:54
> The available MAOIs also have other effects. Phenelzine, for example, increases the amount of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the brain. (To give you an idea of what GABA might have to do with anxiety, consider that benzodiazepines such as Valium, Ativan, Xanax, etc., work by increasing the effectiveness of GABA.) Parnate is thought to have some amphetamine-like (stimulant) effects, although nobody ever bothered to find out what these effects might be (it's an old drug, off patent, and there's little interest in studying it, although there is a lot we could learn).
>> -elizabeth
Does this in anyway mean a benzo added to Nardil will increase the GABA effects? And also does anyone have experience with this and know the effects? Thanks.
-Carlos
Posted by ace on May 5, 2003, at 20:04:16
In reply to Why Is Nardil superior to SSRIs for SP, posted by PaulB on November 29, 2001, at 22:32:57
This is the end of the thread.
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