![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 48 to 72 of 200. Go back in thread:
Posted by Denise528 on February 4, 2002, at 10:07:51
In reply to Re: New Celexa...BORING!, posted by Denise528 on February 4, 2002, at 9:02:36
> > > Just to add, I entirely agree, why do they waste everyones time bringing out yet more SSRIs, surely the choice of SSRIs is wide enough without introducing more of the same. It's so annoying. I've tried the SSRIs and they don't work for me, bring on the CRF Antagonists, that's what I say.
Denise
> >
Posted by ben on February 4, 2002, at 13:07:42
In reply to Re: New Celexa...BORING!, posted by OldSchool on February 3, 2002, at 15:00:31
Hi OldSchool
Why should this be an improvement or breakthrough ? Selegiline is on the market since years and other MAOIs/RIMAs as well.
Pdocs are allowed to use Selegiline for depression without any FDA approval. And dont forget: if MAIOs/RIMAs would work great they would be more prescribed !!! It isnt only the fear of severe blood pression. Venlafaxine is the only one which has been superior to other ADs in several studys including faster onset of action. We dont have any real alternative to Venlafaxine (tricyclics are much more nastier concerning anticholinergic side-effects ) yet...so Duloxetine is welcome.
I agree that we have enough SSRIs and more new mechanisms (e.g. Venlafaxine, Nefadozone, Mirtazapine) should be developped. I read abou the company MERCK investigate an substance which acts like an SSRI BUT including blocking the 5HT1 receptor. From my experience SSRIs are hitting mood much more than Reboxetine/Desipramine....so the serotonine mechanism has to bee present for an AD. I dont know much about the MAO-B inhibitor Selegiline (parkinsons disease). Should it work better than Tranylcypromine or the RIMA Moclobemide ??? Give us some facts, that would be nice.thanks ben
> When is the Selegiline MAOI patch coming out? IS the MAOI patch going to be FDA approved? Now THERE is a real antidepressant!!
>
> Old School
Posted by djmmm on February 4, 2002, at 13:53:15
In reply to Re: New Celexa...BORING! @ OldSchool, posted by ben on February 4, 2002, at 13:07:42
> Hi OldSchool
>
> Why should this be an improvement or breakthrough ? Selegiline is on the market since years and other MAOIs/RIMAs as well.
> Pdocs are allowed to use Selegiline for depression without any FDA approval. And dont forget: if MAIOs/RIMAs would work great they would be more prescribed !!! It isnt only the fear of severe blood pression. Venlafaxine is the only one which has been superior to other ADs in several studys including faster onset of action. We dont have any real alternative to Venlafaxine (tricyclics are much more nastier concerning anticholinergic side-effects ) yet...so Duloxetine is welcome.
> I agree that we have enough SSRIs and more new mechanisms (e.g. Venlafaxine, Nefadozone, Mirtazapine) should be developped. I read abou the company MERCK investigate an substance which acts like an SSRI BUT including blocking the 5HT1 receptor. From my experience SSRIs are hitting mood much more than Reboxetine/Desipramine....so the serotonine mechanism has to bee present for an AD. I dont know much about the MAO-B inhibitor Selegiline (parkinsons disease). Should it work better than Tranylcypromine or the RIMA Moclobemide ??? Give us some facts, that would be nice.
>
> thanks ben
>
> > When is the Selegiline MAOI patch coming out? IS the MAOI patch going to be FDA approved? Now THERE is a real antidepressant!!
> >
> > Old SchoolI can answer your question...everything is based on this study:
http://www.news.harvard.edu/gazette/1998/12.10/depression.html
Posted by ben on February 4, 2002, at 14:26:41
In reply to Re: New Celexa...BORING! @ OldSchool, posted by djmmm on February 4, 2002, at 13:53:15
Sounds good; but response rate (72%) is similar to other ADs (including SSRIs). How many drop outs ? What side effects has been reported and in what incidence they occured - no answer.
Okay, no first pass effect, but it needs as long as oral forms to reach a steady state (undependet of galenic form !). Why sould it work faster/better ? It is possible that fewer side effects are reported because of smaller plasma fluctuations.
Are patches against depression in developement by some companies ? Would be glad if you can report some sources.> I can answer your question...everything is based on this study:
>
> http://www.news.harvard.edu/gazette/1998/12.10/depression.html
Posted by ben on February 4, 2002, at 14:35:27
In reply to Re: New Celexa...BORING!, posted by Denise528 on February 4, 2002, at 10:07:51
I read that CRF antagonists are "only" good to boost response by other ADs and poop out very quickly if they are used alone.
(search under the author named F. Holsboer in PubMed)
> > > > Just to add, I entirely agree, why do they waste everyones time bringing out yet more SSRIs, surely the choice of SSRIs is wide enough without introducing more of the same. It's so annoying. I've tried the SSRIs and they don't work for me, bring on the CRF Antagonists, that's what I say.
>
> Denise
> > >
Posted by OldSchool on February 4, 2002, at 17:55:45
In reply to Re: New Celexa...BORING! @ OldSchool, posted by ben on February 4, 2002, at 13:07:42
> Hi OldSchool
>
> Why should this be an improvement or breakthrough ? Selegiline is on the market since years and other MAOIs/RIMAs as well.
> Pdocs are allowed to use Selegiline for depression without any FDA approval. And dont forget: if MAIOs/RIMAs would work great they would be more prescribed !!! It isnt only the fear of severe blood pression. Venlafaxine is the only one which has been superior to other ADs in several studys including faster onset of action. We dont have any real alternative to Venlafaxine (tricyclics are much more nastier concerning anticholinergic side-effects ) yet...so Duloxetine is welcome.
> I agree that we have enough SSRIs and more new mechanisms (e.g. Venlafaxine, Nefadozone, Mirtazapine) should be developped. I read abou the company MERCK investigate an substance which acts like an SSRI BUT including blocking the 5HT1 receptor. From my experience SSRIs are hitting mood much more than Reboxetine/Desipramine....so the serotonine mechanism has to bee present for an AD. I dont know much about the MAO-B inhibitor Selegiline (parkinsons disease). Should it work better than Tranylcypromine or the RIMA Moclobemide ??? Give us some facts, that would be nice.
>
> thanks ben
>Ben, I am fully aware Selegiline can already currently be used off label for depression. In pill form. In fact I had a discussion about using selegiline the last time I saw my psychiatrist. However in this pill form if you go above the usual parkinsons dose of 10 mg a day, Selegiline becomes an irreversible MAOI and the "cheese effect" kicks in. Thus at the dosages needed to fight resistant depression, you must go on the MAOI diet with oral selegiline.
The whole point of this new MAOI patch that uses selegiline is that it is not oral, it bypasses the gut and liver and goes directly into your bloodstream like a needle shot. This reportedly eliminates the need for the troublesome MAOI diet and dramatically decreases, probably pretty much eliminates the possibility of an MAOI hypertensive crisis. I dont know about you my friend, but to me this represents a quantum leap ahead in psychopharmacology. MAOIs are by far the best antidepressants. MAOIs are very useful for refractory depression. But the current problem is quite a few folks could benefit from this robust MAOI antidepressant effect but are turned off bigtime by the idea of the MAOI diet and the possibility of having a stroke. No pepperoni pizzas, no maccaroni and cheese, no subs at Jersey Mikes. And the looming possibility your blood pressure could suddenly spike sky high, sending you to the ER and possibly even have a stroke. Ever seen someone who had a stroke and survived? Trust me, its way worse than the worst case of depression.
The patch dramatically decreases all of these MAOI problems Ben. Thats why I would like to see this patch FDA approved. Keep in mind youd still have to go by the drug restrictions list if on the MAOI patch, as drugs go into the bloodstream. So you could ditch the MAOI diet, eat cheese all the time but would still have to restrict various drugs that can interact with MAOIs.
Do you see my point? The selegiline MAOI patch kicks the shit out of a "new and improved" Celexa. Its a truly good idea thats truly unique. Someone actually put their brain into this one. New Celexa is just another "me too" SSRI. Boring.
Eric
Posted by manowar on February 4, 2002, at 23:36:15
In reply to Re: New Celexa...BORING! @ OldSchool, posted by OldSchool on February 4, 2002, at 17:55:45
Hello Eric,
Why would the delivery method of the drug have any impact on the MAOI mechanism which causes the cheese effect?Just curious,
Tim
> > Hi OldSchool
> >
> > Why should this be an improvement or breakthrough ? Selegiline is on the market since years and other MAOIs/RIMAs as well.
> > Pdocs are allowed to use Selegiline for depression without any FDA approval. And dont forget: if MAIOs/RIMAs would work great they would be more prescribed !!! It isnt only the fear of severe blood pression. Venlafaxine is the only one which has been superior to other ADs in several studys including faster onset of action. We dont have any real alternative to Venlafaxine (tricyclics are much more nastier concerning anticholinergic side-effects ) yet...so Duloxetine is welcome.
> > I agree that we have enough SSRIs and more new mechanisms (e.g. Venlafaxine, Nefadozone, Mirtazapine) should be developped. I read abou the company MERCK investigate an substance which acts like an SSRI BUT including blocking the 5HT1 receptor. From my experience SSRIs are hitting mood much more than Reboxetine/Desipramine....so the serotonine mechanism has to bee present for an AD. I dont know much about the MAO-B inhibitor Selegiline (parkinsons disease). Should it work better than Tranylcypromine or the RIMA Moclobemide ??? Give us some facts, that would be nice.
> >
> > thanks ben
> >
>
> Ben, I am fully aware Selegiline can already currently be used off label for depression. In pill form. In fact I had a discussion about using selegiline the last time I saw my psychiatrist. However in this pill form if you go above the usual parkinsons dose of 10 mg a day, Selegiline becomes an irreversible MAOI and the "cheese effect" kicks in. Thus at the dosages needed to fight resistant depression, you must go on the MAOI diet with oral selegiline.
>
> The whole point of this new MAOI patch that uses selegiline is that it is not oral, it bypasses the gut and liver and goes directly into your bloodstream like a needle shot. This reportedly eliminates the need for the troublesome MAOI diet and dramatically decreases, probably pretty much eliminates the possibility of an MAOI hypertensive crisis. I dont know about you my friend, but to me this represents a quantum leap ahead in psychopharmacology. MAOIs are by far the best antidepressants. MAOIs are very useful for refractory depression. But the current problem is quite a few folks could benefit from this robust MAOI antidepressant effect but are turned off bigtime by the idea of the MAOI diet and the possibility of having a stroke. No pepperoni pizzas, no maccaroni and cheese, no subs at Jersey Mikes. And the looming possibility your blood pressure could suddenly spike sky high, sending you to the ER and possibly even have a stroke. Ever seen someone who had a stroke and survived? Trust me, its way worse than the worst case of depression.
>
> The patch dramatically decreases all of these MAOI problems Ben. Thats why I would like to see this patch FDA approved. Keep in mind youd still have to go by the drug restrictions list if on the MAOI patch, as drugs go into the bloodstream. So you could ditch the MAOI diet, eat cheese all the time but would still have to restrict various drugs that can interact with MAOIs.
>
> Do you see my point? The selegiline MAOI patch kicks the shit out of a "new and improved" Celexa. Its a truly good idea thats truly unique. Someone actually put their brain into this one. New Celexa is just another "me too" SSRI. Boring.
>
> Eric
Posted by manowar on February 4, 2002, at 23:51:31
In reply to Reason For Release of New Drugs, posted by IsoM on January 31, 2002, at 17:04:53
> The development of the new Celexa is meant to be an improvement in its effectiveness - it's meant to have fewer side-effects. Most of the side-effects experienced comes from the ineffective isomer of Celexa. Take that away & you'll still get the same response as you did to the old Celexa but without as many troubling side-effects.
>
> There are teams of earnest young scientists working together to come up with new ADs but drugs can only be chemically engineered & carefully tailored for each specific need as more is learned about how our body's many functions interact. That's why one class is called "Selective" serotonin reuptake inhibitors. There's many sites throughout the body where serotonin has its effects, these try to target slective sites. If drugs could be even more tailored to just fit the ones that need to be targeted - result is more effective meds with fewer side-effects.
>
> Drug engineering is really only in its infancy. We're only at the "leeches & blood-letting" stage, so to speak, but at this point in time, it's the best we've got. Would it be more cruel to hold back simply because we haven't progressed enough? Or to provide treatment such as we have now?
>
> (Not to say I don't think pharmaceutical firms don't push their products forcefully on the market - but that's another story.)Hello,
Maybe the drug manufacturers need to get off the "selective" kick and start working on a more shotgun like approach for antidepressants.
The *finil drugs effect several different neurotransmitter sites, and they are very effective for some folks like you and me. Serzone also seems to have a "shotgun" effect on various neurotransmitters.Just thought I'd throw in my two cents worth.
Tim
Posted by Ritch on February 4, 2002, at 23:55:31
In reply to Re: New Celexa...BORING! @ OldSchool, posted by OldSchool on February 4, 2002, at 17:55:45
Fascinating discussion (and link) about transdermal antidepressant application of selegiline. What about using a transdermal application for folks that happen to respond to SSRI's (like me), but who have nasty GI side effects from the extra serotonin released from all of the cells that line the GI tract (dyspepsia, GERD, diarrhea)? I wonder if there could be any benefit.Mitch
Posted by IsoM on February 5, 2002, at 0:24:27
In reply to What's wrong with the shotgun approach? » IsoM, posted by manowar on February 4, 2002, at 23:51:31
I got talking with a chemical engineer once(he wasn't in medicine development though) which is how I learned a bit more about new drug development, plus I did a whole lot more reading.
Drug development can be really complicated. Shotgun approach is tried but the more sites affected, the more likely it is to have more side-effects too. It's not the chemical engineering that lags but the knowledge of how the brain & different transmitters work. More research is needed on how the mind works. At least, we seemed to have found our "magic bullet".
You probably didn't see one post where I asked if your deep sleep stage has improved at all on the modafinil. I'm curious but don't know whether you had trouble sleeping before.
Posted by djmmm on February 5, 2002, at 1:57:51
In reply to Re: What about SSRI patch to bypass GI tract?, posted by Ritch on February 4, 2002, at 23:55:31
>
> Fascinating discussion (and link) about transdermal antidepressant application of selegiline. What about using a transdermal application for folks that happen to respond to SSRI's (like me), but who have nasty GI side effects from the extra serotonin released from all of the cells that line the GI tract (dyspepsia, GERD, diarrhea)? I wonder if there could be any benefit.
>
> Mitchselegiline is a very unique compound, not all antidepressants can be absorbed through the skin...in fact, I don't think any other antidepressants can, so a SSRI patch is out of the question.
Posted by ben on February 5, 2002, at 2:45:48
In reply to Re: New Celexa...BORING! @ OldSchool, posted by OldSchool on February 4, 2002, at 17:55:45
Cheese like effect: Tyramine is like a prodrug of noradrenaline, so eating food including much tyramine elevates the noradrenaline level. MAOIs inhibit the turn over to inactive metabolites of noradrenaline (dopamine and serotonin) like 3-OH-noradrenaline. MAOIs do influence the MAO in the brain much more than in the liver (plasma levels of of monamines are not very high compared with concentrations in the brain) Patches do only affect the first pass metabolism in the liver so you have do give less amounts of the drug reaching a similar plasma level. So why should the patch do not have the cheese like effect ? The drug mechanism is the same, as well as the final elimination through the liver.¨
> > Hi OldSchool
> >
> > Why should this be an improvement or breakthrough ? Selegiline is on the market since years and other MAOIs/RIMAs as well.
> > Pdocs are allowed to use Selegiline for depression without any FDA approval. And dont forget: if MAIOs/RIMAs would work great they would be more prescribed !!! It isnt only the fear of severe blood pression. Venlafaxine is the only one which has been superior to other ADs in several studys including faster onset of action. We dont have any real alternative to Venlafaxine (tricyclics are much more nastier concerning anticholinergic side-effects ) yet...so Duloxetine is welcome.
> > I agree that we have enough SSRIs and more new mechanisms (e.g. Venlafaxine, Nefadozone, Mirtazapine) should be developped. I read abou the company MERCK investigate an substance which acts like an SSRI BUT including blocking the 5HT1 receptor. From my experience SSRIs are hitting mood much more than Reboxetine/Desipramine....so the serotonine mechanism has to bee present for an AD. I dont know much about the MAO-B inhibitor Selegiline (parkinsons disease). Should it work better than Tranylcypromine or the RIMA Moclobemide ??? Give us some facts, that would be nice.
> >
> > thanks ben
> >
>
> Ben, I am fully aware Selegiline can already currently be used off label for depression. In pill form. In fact I had a discussion about using selegiline the last time I saw my psychiatrist. However in this pill form if you go above the usual parkinsons dose of 10 mg a day, Selegiline becomes an irreversible MAOI and the "cheese effect" kicks in. Thus at the dosages needed to fight resistant depression, you must go on the MAOI diet with oral selegiline.
>
> The whole point of this new MAOI patch that uses selegiline is that it is not oral, it bypasses the gut and liver and goes directly into your bloodstream like a needle shot. This reportedly eliminates the need for the troublesome MAOI diet and dramatically decreases, probably pretty much eliminates the possibility of an MAOI hypertensive crisis. I dont know about you my friend, but to me this represents a quantum leap ahead in psychopharmacology. MAOIs are by far the best antidepressants. MAOIs are very useful for refractory depression. But the current problem is quite a few folks could benefit from this robust MAOI antidepressant effect but are turned off bigtime by the idea of the MAOI diet and the possibility of having a stroke. No pepperoni pizzas, no maccaroni and cheese, no subs at Jersey Mikes. And the looming possibility your blood pressure could suddenly spike sky high, sending you to the ER and possibly even have a stroke. Ever seen someone who had a stroke and survived? Trust me, its way worse than the worst case of depression.
>
> The patch dramatically decreases all of these MAOI problems Ben. Thats why I would like to see this patch FDA approved. Keep in mind youd still have to go by the drug restrictions list if on the MAOI patch, as drugs go into the bloodstream. So you could ditch the MAOI diet, eat cheese all the time but would still have to restrict various drugs that can interact with MAOIs.
>
> Do you see my point? The selegiline MAOI patch kicks the shit out of a "new and improved" Celexa. Its a truly good idea thats truly unique. Someone actually put their brain into this one. New Celexa is just another "me too" SSRI. Boring.
>
> Eric
Posted by OldSchool on February 5, 2002, at 20:48:02
In reply to No cheese effect?--COOL-but how? » OldSchool, posted by manowar on February 4, 2002, at 23:36:15
> Hello Eric,
> Why would the delivery method of the drug have any impact on the MAOI mechanism which causes the cheese effect?
>
> Just curious,
>Cause when the MAOI is given directly into the skin as with a patch, the gut is bypassed and the drug goes directly into your bloodstream. If the drug bypasses the gut, no food reactions. No MAOI diet required. Of course the drug restrictions still will apply. But reportedly no food restrictions.
Now you tell me if that would not be some shit or what? If you could take an MAOI but no MAOI diet?
Old School
Posted by OldSchool on February 5, 2002, at 20:58:49
In reply to Re: New Celexa...BORING! @ OldSchool, posted by ben on February 5, 2002, at 2:45:48
> Cheese like effect: Tyramine is like a prodrug of noradrenaline, so eating food including much tyramine elevates the noradrenaline level. MAOIs inhibit the turn over to inactive metabolites of noradrenaline (dopamine and serotonin) like 3-OH-noradrenaline. MAOIs do influence the MAO in the brain much more than in the liver (plasma levels of of monamines are not very high compared with concentrations in the brain) Patches do only affect the first pass metabolism in the liver so you have do give less amounts of the drug reaching a similar plasma level. So why should the patch do not have the cheese like effect ? The drug mechanism is the same, as well as the final elimination through the liver.¨
>
Look Ben, this stuff isnt my idea. I am just repeating stuff Ive read about this MAOI patch. The FDA pulled the MAOI diet requirements in the clinical trials for this patch. The things Ive read about it say the drug bypasses the gut, unlike with oral forms of MAOIs and this eliminates the need for the MAOI diet.This link explains some of it:
http://www.news.harvard.edu/gazette/1998/12.10/depression.html
< quoted from above article >
>The FDA eliminated dietary restrictions for >those in the new study, now getting under way. "When given through the skin, selegiline finally removes the need for such restrictions," >Bodkin says.
Here is another link that mentions no need for the MAOI diet with the selegiline MAOI patch:
http://www.mhsource.com/expert/exp1051500c.html
>The "MAOI patch" is being tested at McLean >Hosptial in Belmont Mass, under the direction of >Dr. Alexander Bodkin. The patch uses an antidepressant called selegiline [Eldepryl], which is a MAOI (monoamine oxidase inhibitor). Unlike standard MAOI tablets, the "patch" bypasses the gut, and should allow a normal diet to be used by the patient. Keep in mind, of course, that standard MAOI tablets have been available for decades, and may be very helpful in some cases of severe, resistant depression; however, a special diet is required for their use, as you may know
Eric
Posted by djmmm on February 5, 2002, at 22:44:52
In reply to Re: New Celexa...BORING! @ OldSchool, posted by OldSchool on February 5, 2002, at 20:58:49
> > Cheese like effect: Tyramine is like a prodrug of noradrenaline, so eating food including much tyramine elevates the noradrenaline level. MAOIs inhibit the turn over to inactive metabolites of noradrenaline (dopamine and serotonin) like 3-OH-noradrenaline. MAOIs do influence the MAO in the brain much more than in the liver (plasma levels of of monamines are not very high compared with concentrations in the brain) Patches do only affect the first pass metabolism in the liver so you have do give less amounts of the drug reaching a similar plasma level. So why should the patch do not have the cheese like effect ? The drug mechanism is the same, as well as the final elimination through the liver.¨
> >
>
>
> Look Ben, this stuff isnt my idea. I am just repeating stuff Ive read about this MAOI patch. The FDA pulled the MAOI diet requirements in the clinical trials for this patch. The things Ive read about it say the drug bypasses the gut, unlike with oral forms of MAOIs and this eliminates the need for the MAOI diet.
>
> This link explains some of it:
>
> http://www.news.harvard.edu/gazette/1998/12.10/depression.html
>
> < quoted from above article >
>
> >The FDA eliminated dietary restrictions for >those in the new study, now getting under way. "When given through the skin, selegiline finally removes the need for such restrictions," >Bodkin says.
>
> Here is another link that mentions no need for the MAOI diet with the selegiline MAOI patch:
>
> http://www.mhsource.com/expert/exp1051500c.html
>
> >The "MAOI patch" is being tested at McLean >Hosptial in Belmont Mass, under the direction of >Dr. Alexander Bodkin. The patch uses an antidepressant called selegiline [Eldepryl], which is a MAOI (monoamine oxidase inhibitor). Unlike standard MAOI tablets, the "patch" bypasses the gut, and should allow a normal diet to be used by the patient. Keep in mind, of course, that standard MAOI tablets have been available for decades, and may be very helpful in some cases of severe, resistant depression; however, a special diet is required for their use, as you may know
>
> Eric
Eric,also... by bypassing first pass metabolism, the l-amphetamine, and l-methamphetamine metablites are avoided...
Im confused because Selegiline is a poor antidepressant (typically), Do you know the amount of selegiline absorbed through the skin? is it high enough that it is no longer selective to MAO-B?....
...also you still have to avoid all the medications that are on the MAOI list (ephedra, dextromethorphan, ventolin, etc)
just some links:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7519005&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2491941&dopt=Abstract
)
Posted by Ritch on February 6, 2002, at 1:02:54
In reply to Re: What about SSRI patch to bypass GI tract?, posted by djmmm on February 5, 2002, at 1:57:51
> >
> > Fascinating discussion (and link) about transdermal antidepressant application of selegiline. What about using a transdermal application for folks that happen to respond to SSRI's (like me), but who have nasty GI side effects from the extra serotonin released from all of the cells that line the GI tract (dyspepsia, GERD, diarrhea)? I wonder if there could be any benefit.
> >
> > Mitch
>
> selegiline is a very unique compound, not all antidepressants can be absorbed through the skin...in fact, I don't think any other antidepressants can, so a SSRI patch is out of the question.
I just remembered something that probably isn't too important...but..doxepin (Sinequan, Adapin, a TCA antidepressant) used to be available as a topical cream for dermatitis and hives, etc. a topical antihistamine. From what I recall there were warnings about using the cream over large areas of the body due to the absorption of the medication through the skin and it entering the bloodstream.Perhaps more transdermal applications of medications are not ventured because of factors other than *impossibility*. Perhaps it is not *easy* to do, not *practical*, or *marketable*. (little return on investment??)
Mitch
Posted by djmmm on February 6, 2002, at 2:25:40
In reply to Re: What about other AD transdermal patches? » djmmm, posted by Ritch on February 6, 2002, at 1:02:54
> > >
> > > Fascinating discussion (and link) about transdermal antidepressant application of selegiline. What about using a transdermal application for folks that happen to respond to SSRI's (like me), but who have nasty GI side effects from the extra serotonin released from all of the cells that line the GI tract (dyspepsia, GERD, diarrhea)? I wonder if there could be any benefit.
> > >
> > > Mitch
> >
> > selegiline is a very unique compound, not all antidepressants can be absorbed through the skin...in fact, I don't think any other antidepressants can, so a SSRI patch is out of the question.
>
>
> I just remembered something that probably isn't too important...but..doxepin (Sinequan, Adapin, a TCA antidepressant) used to be available as a topical cream for dermatitis and hives, etc. a topical antihistamine. From what I recall there were warnings about using the cream over large areas of the body due to the absorption of the medication through the skin and it entering the bloodstream.
>
> Perhaps more transdermal applications of medications are not ventured because of factors other than *impossibility*. Perhaps it is not *easy* to do, not *practical*, or *marketable*. (little return on investment??)
>
> Mitch
I was wrong...after some searching, it seems that Buspar was tested in transdermal form, too.
Posted by Mr. Scott on February 6, 2002, at 3:58:06
In reply to Forest Labs gets US conditional approval for Lexa., posted by bonnie_ann on January 28, 2002, at 20:01:34
I've heard that elevated glucocortical hormone (the bodies cortisone)level is what may be responsible in the end for depression and Hippocampus damage. In a roundabout way SSRI's and Tricyclics seem to increase the uptake of glucocortical hormone I also remember hearing. Maybe there is a better way to accomplish this.
Scott
Posted by ben on February 6, 2002, at 7:48:47
In reply to Re: No cheese effect?--COOL-but how?, posted by OldSchool on February 5, 2002, at 20:48:02
I read the german monographies from Selegiline and Moclobemide ant it tells you the following:
1.Selegiline is a irreversible MAO-B inhibitor at low doses (5-10 mg/d p.o.) and loses the selectivity (inhibition of MAO-A too) at higher doses. There is no diet restriction needed BUT it is recommended to avoid tyramine rich food like cheddar...
2. Moclobemideis a reversible MAO-A inhibitor at low doses (-600 mg/d p.o.) and loses the selectivity (inhibition of MAO-B too) when given in higher doses (I guess more than 600/900 mg a day).There is no diet restriction needed BUT it is recommended to avoid tyramine rich food like cheddar...
Some pdocs use Moclobemide up to 1200 mg a day under blood pressure control if patients had only partial response OR are ultra rapid metabolizers (mephenytoin-polymorphism) !Conclusion: No diet restriction for Selegiline and Moclobemide in usual doses. The Cheese-like effect is mechanism based ! - and undepended of the drug form (oral/transdermal/i.v....).
Some points about the amphetamine-like metabolites:
-Do they occur only after first pass metabolism (I dont guess so because your body has to get rid of lipophilic drugs mostly over the liver ) !?
If they have really significant effects we should know the half-life of them and the therapeutic window - to see if our discussion about is really relevant.
-Thought they have no real amphetamine-like effects (and no bad side effects). Is this not an anectotal or are there new informations ?> Now you tell me if that would not be some shit or what? If you could take an MAOI but no MAOI diet?
>
> Old School
Posted by Ritch on February 6, 2002, at 9:37:49
In reply to Re: What about other AD transdermal patches?, posted by djmmm on February 6, 2002, at 2:25:40
> > > >
> > > > Fascinating discussion (and link) about transdermal antidepressant application of selegiline. What about using a transdermal application for folks that happen to respond to SSRI's (like me), but who have nasty GI side effects from the extra serotonin released from all of the cells that line the GI tract (dyspepsia, GERD, diarrhea)? I wonder if there could be any benefit.
> > > >
> > > > Mitch
> > >
> > > selegiline is a very unique compound, not all antidepressants can be absorbed through the skin...in fact, I don't think any other antidepressants can, so a SSRI patch is out of the question.
> >
> >
> > I just remembered something that probably isn't too important...but..doxepin (Sinequan, Adapin, a TCA antidepressant) used to be available as a topical cream for dermatitis and hives, etc. a topical antihistamine. From what I recall there were warnings about using the cream over large areas of the body due to the absorption of the medication through the skin and it entering the bloodstream.
> >
> > Perhaps more transdermal applications of medications are not ventured because of factors other than *impossibility*. Perhaps it is not *easy* to do, not *practical*, or *marketable*. (little return on investment??)
> >
> > Mitch
>
>
> I was wrong...after some searching, it seems that Buspar was tested in transdermal form, too.
>
> http://www.pslgroup.com/dg/2C1AE.htmWow, I just got another idea here. Maybe a lot of the transdermal delivery research on existing meds has precisely to do with profits?
Buspar is fixing to go generic soon I believe...
that is in pill form.
New delivery systems would guarantee the patent status of that formulation and maintain the income stream from the medication. All of the engineering costs would be involved with the delivery system alone, and subsequent trials wouldn't be as much of a dice throw-as there is already extensive clinical experience with the oral form..hmmmm.Mitch
Posted by ben on February 6, 2002, at 10:41:15
In reply to Glucocorticoid Sucker Upper, posted by Mr. Scott on February 6, 2002, at 3:58:06
If you are interested: make a research in PuMed under the author F. Holsboer (published a lot about CRF/CRH and mood disorders)
Unfortunately it isnt the HPA-axis alone causing depression !
> I've heard that elevated glucocortical hormone (the bodies cortisone)level is what may be responsible in the end for depression and Hippocampus damage. In a roundabout way SSRI's and Tricyclics seem to increase the uptake of glucocortical hormone I also remember hearing. Maybe there is a better way to accomplish this.
> Scott
Posted by OldSchool on February 6, 2002, at 12:05:12
In reply to Re: New Celexa...BORING! @ OldSchool, posted by djmmm on February 5, 2002, at 22:44:52
>
>
> Eric,
>
> also... by bypassing first pass metabolism, the l-amphetamine, and l-methamphetamine metablites are avoided...
>
> Im confused because Selegiline is a poor antidepressant (typically), Do you know the amount of selegiline absorbed through the skin? is it high enough that it is no longer selective to MAO-B?....
>
> ...also you still have to avoid all the medications that are on the MAOI list (ephedra, dextromethorphan, ventolin, etc)
>
> just some links:
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7519005&dopt=Abstract
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2491941&dopt=Abstract
> )
Well, selegiline at the doses used for parkinsons is a poor antidepressant from what Ive read. The dose used for parkinsons is 10 mg. At this low a dose selegiline is a selective MAOI, for MAO-B only. At the 10 mg dose used for parkinsons you do not get any MAO-A. MAO-A is where you get the real antidepressant effect from. Parnate, Nardil and Marplan are all irreversible MAOIs and increase both MAO-B and MAO-A at the same time.From what Ive read Selegiline is a pretty good antidepressant IF you take higher doses of it, much higher than 10 mg. At higher doses of selegiline, it loses its selectivity for MAO-B and begins increasing MAO-A. Thus the antidepressant effect kicks in. The problem with this is that as soon as selegiline begins becoming irreversible at the high doses needed to be an antidepressant, the "cheese effect" kicks in as selegiline becomes a plain old regular MAOI like Parnate. Thus the MAOI diet must be followed with dosages above 10 mg.
I read all this stuff over on the tips and tricks of this site. Just look up MAOIs and pick the selegiline link.
Posted by Bekka H. on February 6, 2002, at 19:15:21
In reply to Re: Forest Labs gets US conditional approval for Lexa., posted by OldSchool on January 31, 2002, at 16:49:29
> > This is so stupid. Another new SSRI. We already have enough SSRIs on the market, we dont need more. Instead of newer SSRIs how about something new and novel? Like substance P, MAOI patches, etc. This "new and improved" SSRI gets FDA approval? LOL How much do you wanna bet the new selegiline MAOI patch gets shot down by the FDA? A drug that could actually make a difference like the MAOI patch will probably not get passed, but more "me too" SSRIs glide thru easily.
> > > What a crock.
> > > Old School
> Scott, I seriously doubt any real treatment resistant people are going to be helped by a "new and improved" Celexa. Get real. Its a waste of time. Celexa is already good enough. Develop another kind of drug and move on.
> Old School************************************************
Old School, those are my sentiments exactly! I've had it with those wimpogenic, fat-causing, impotence causing, sedating, apathy-producing compounds. I have yet to understand how a drug that makes most people fat, impotent, wimpy blobs could be considered an ANTIDEPRESSANT. It's all in the marketing and in paying off the doctors who run the clinical trials to tell the public what it wants to hear. I believe that there MIGHT be a few exceptions, but most of the people I know of who have been on SSRIs are not happy with the results. Quite frankly, I think the SSRIs are quite dangerous in some cases. Patients get so apathetic on them that they stop caring that they don't care; consequently, they are unlikely to report some of these adverse effects to their doctors. And I think a lot of doctors like the SSRIs because their patients get so wimpy and complacent on them that they don't bother their shrinks as much. They stop complaining about things they should be complaining about, and their docs can spend more time thinking about golf or the stock market.
I'd also like to know why these scientists can't come up with an effective drug that doesn't cause weight gain. And, if they did produce such a drug (for example, a Remeron-type medicine WITHOUT the Remeron weight gain), I'll bet the FDA wouldn't even approve it. They'd be too afraid that, like amineptine, it might make people feel too good (Oh my Lord, what a concept!), and they'd ban it for eternity.
Posted by OldSchool on February 7, 2002, at 10:54:38
In reply to Re: Forest Labs gets US conditional approval for Lexa., posted by Bekka H. on February 6, 2002, at 19:15:21
> Old School, those are my sentiments exactly! I've had it with those wimpogenic, fat-causing, impotence causing, sedating, apathy-producing compounds. I have yet to understand how a drug that makes most people fat, impotent, wimpy blobs could be considered an ANTIDEPRESSANT.
The above side effects are the least of my concerns. I could care less an antidepressant makes me gain some weight or causes sexual dysfunction. My beef with the SSRIs is that these drugs simply DO NOT WORK good enough in a percentage of depressed people...approximately 20% to 30% of those with major depression. For me, SSRIs are better than nothing and I take them gladly. The side effect profile to me is rather benign considering the severity of my depression when Im off medication. As I said before, I could give a f*ck about SSRI side effects. My attitude is "suck it up" at least it makes your depression better. At least the SSRIs allow me to sleep and stuff.
But again, Id like to see something better developed. Im not anti-SSRI by any means. I think SSRIs are great meds and work for the majority. Just not for everybody. What about those people? What happens to them? Are they just f*cked for the rest of their life, relegated to a life of disability, maintenance ECT and hanging out on psychobabble, looking for that next "better" drug?
>It's all in the marketing and in paying off the doctors who run the clinical trials to tell the public what it wants to hear. I believe that there MIGHT be a few exceptions, but most of the people I know of who have been on SSRIs are not happy with the results. Quite frankly, I think the SSRIs are quite dangerous in some cases. Patients get so apathetic on them that they stop caring that they don't care; consequently, they are unlikely to report some of these adverse effects to their doctors. And I think a lot of doctors like the SSRIs because their patients get so wimpy and complacent on them that they don't bother their shrinks as much. They stop complaining about things they should be complaining about, and their docs can spend more time thinking about golf or the stock market.
>
> I'd also like to know why these scientists can't come up with an effective drug that doesn't cause weight gain. And, if they did produce such a drug (for example, a Remeron-type medicine WITHOUT the Remeron weight gain), I'll bet the FDA wouldn't even approve it. They'd be too afraid that, like amineptine, it might make people feel too good (Oh my Lord, what a concept!), and they'd ban it for eternity.Weight gain is not a concern of mine. When youve been to the bottom of the pit...super duper severe clinical depression and your sleep locks up on you and you lose 20 or 30 lbs without even trying...you get to a point where you could care less about weight gain from drugs.
Id like to see some antidepressants developed SPECIFICALLY for that 20% to 30% of depressives who do not adequately respond to SSRIs, Effexor or tricyclics. Side effects for me is a nonissue...as long as it activates good consistently for long periods without poop out, restores my cognition, sleeping and ability to work would be satisfactory to me.
Old School
Posted by spike4848 on February 8, 2002, at 0:30:47
In reply to Re: Forest Labs gets US conditional approval for Lexa., posted by OldSchool on February 7, 2002, at 10:54:38
>My beef with the SSRIs is that these drugs simply DO NOT WORK good enough in a percentage of depressed people...approximately 20% to 30% of those with major depression.> Old School
Once again .... I totally agree with Old School. And if you press the pdocs hard enough, they will admit that the SSRIs are pretty weak antidepressants compared to the TCAs/MAOIs. They will tell you that the quality response to SSRIs is moderate at best .... the patients are still impaired. SSRIs are basically mindless to prescribe for the pdocs .... dosing is easy, little risk of OD, fewer drug interactions and lots of perks from the drug representative (dinner, gifts, etc). And the drug studies are designed by idiots .... they say a patient whose symptoms decrease by 50% is a responder to a medication. Take my symptoms and decrease them by 50% and I just can make it out of bed. I don't call that a response.
Donald Klein .... one of the Godfathers of psychiatry from Columbia ..... is currently making a HUGE beef with todays drug trials and drug companies. He is breaking the silence amongst the pdoc and pushing for better drug trials. Trials with stricter definitions of response and including patients with moderate to severe depression. He is calling to revamp the whole system ..... he admits that there are still up to 30-50% of patients with no response or inadequate response to medications. Finally a pdoc with some guts!
So giving the world the isomer of Celexa just doesn't cut it for me and so many millions of patients with severe depression ...... give us a potent med to knock the crap out of the this depression.
Spike
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