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Dr. Bob is Robert Hsiung, MD,
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Posted by OldSchool on February 2, 2002, at 18:12:13
In reply to Prozac one went south! » ben, posted by Mr. Scott on February 2, 2002, at 17:53:24
> > No. r-citalopram is supposed to responsible for the side-effects, at least for more side effects than s-citalopram. Thats why they leave the r-isomere away. Lilly is planning this with Prozac (fluoxetine) too.
>
>
> The Prozac one didn't work out for Lilly because at higher doses R-Fluoxetine caused cardiac side effects. That has been ditched... The next big hope out of Lilly is Duloxetine. Another dual acting pump inhibitor.What a waste of time. We already have Effexor...same exact thing as Duloxetine.
Old School
>
> Scott
Posted by djmmm on February 2, 2002, at 23:52:59
In reply to Re: Prozac one went south!, posted by OldSchool on February 2, 2002, at 18:12:13
> > > No. r-citalopram is supposed to responsible for the side-effects, at least for more side effects than s-citalopram. Thats why they leave the r-isomere away. Lilly is planning this with Prozac (fluoxetine) too.
> >
> >
> > The Prozac one didn't work out for Lilly because at higher doses R-Fluoxetine caused cardiac side effects. That has been ditched... The next big hope out of Lilly is Duloxetine. Another dual acting pump inhibitor.
>
> What a waste of time. We already have Effexor...same exact thing as Duloxetine.
>
> Old School
> >
> > Scottoldschool,
Here's something, it's the (R) isomer of sibutramine (meridia)..it will be marketed for depression and ADHD...this may be interesting because it seems to be more selective to norepinephrine and dopamine than serotonin.
http://www.sepracor.com/pharm/
Posted by likewater on February 3, 2002, at 0:22:37
In reply to Re: Prozac one went south!, posted by djmmm on February 2, 2002, at 23:52:59
Everyone is aying that this will be barely better except for side effects.
Assuming this study is correct in addition to less side effects lexpro shows a quicker esponse time.An excert from Yahoo business:
A pooled analysis of two earlier randomized, double-blind, flexible-dose, placebo-controlled studies with a total of 844 patients showed that patients with major depressive disorder who were treated with either escitalopram or Celexa showed significantly greater improvement than depressed patients receiving placebo. Dosing of escitalopram and Celexa was adjusted as needed at specified intervals during the eight-week studies. Escitalopram was dosed at 10 mg or 20 mg per day, with a mean daily dose of 12.6 mg throughout the studies; Celexa was dosed at either 20 mg or 40 mg per day with a mean daily dose of 25.5 mg throughout the studies. The analysis showed that escitalopram and Celexa were both statistically superior to placebo on all efficacy measures. However, this superiority was demonstrated by escitalopram in the first week of treatment and later in the study by Celexa.
Posted by Cecilia on February 3, 2002, at 2:44:38
In reply to Re: Prozac one went south!, posted by OldSchool on February 2, 2002, at 18:12:13
Anyone have any info on duloxetine-when it`s coming out, side effects, how it differs from Effexor(which was pure poison for me even at half a 25 mg tablet)? Cecilia
Posted by IsoM on February 3, 2002, at 3:31:45
In reply to I disagree, posted by likewater on February 3, 2002, at 0:22:37
It may very well be that anyone taking escitalopram shows a faster response than on Celexa, but my son & I were both very surprised to find that we initially responded to Celexa in just under a week, though it took longer for full benefits to be felt. I've never responded to any ADs in such a short time frame. Most took around 3 weeks before I noticed anything.
I can't see why escitalopram would be quicker unless side-effects felt 'muffled' the initial response for many.
Posted by Ritch on February 3, 2002, at 10:29:48
In reply to Re: Duloxetine, posted by Cecilia on February 3, 2002, at 2:44:38
> Anyone have any info on duloxetine-when it`s coming out, side effects, how it differs from Effexor(which was pure poison for me even at half a 25 mg tablet)? Cecilia
Hi Cecilia,From what I found it appears that it will be sometime this year. Here are a couple of links, one discusses duloxetine, and I have thrown in another one for atomoxetine for ADHD, for anybody else who is interested. Interesting that these two are both being marketed by Lilly. Fluoxetine appears to have some interesting chemical cousins...
Mitch
http://www.additudemag.com/medical.asp?DEPT_NO=505&SUB_NO=9
http://www.mhsource.com/pt/mhe18-hourglass.html
Posted by Geezer on February 3, 2002, at 11:29:57
In reply to Re: Duloxetine Atomoxetine » Cecilia, posted by Ritch on February 3, 2002, at 10:29:48
> > Anyone have any info on duloxetine-when it`s coming out, side effects, how it differs from Effexor(which was pure poison for me even at half a 25 mg tablet)? Cecilia
>
>
> Hi Cecilia,
>
> From what I found it appears that it will be sometime this year. Here are a couple of links, one discusses duloxetine, and I have thrown in another one for atomoxetine for ADHD, for anybody else who is interested. Interesting that these two are both being marketed by Lilly. Fluoxetine appears to have some interesting chemical cousins...
>
> Mitch
>
> http://www.additudemag.com/medical.asp?DEPT_NO=505&SUB_NO=9
> http://www.mhsource.com/pt/mhe18-hourglass.htmlHi Cecilia,
For what its worth, I contacted Lilly by phone RE: Duloxetine. Customer service informs me they expect release late 2002. You still have to factor in the strong possibility the FDA will screw-up the whole business so there could be further delays. Seems like you had a typical response to "Side-Effexor".
Mitch - thanks for the article, it helps.
Geezer
Posted by Mr. Scott on February 3, 2002, at 12:43:59
In reply to I disagree, posted by likewater on February 3, 2002, at 0:22:37
My understanding is that these are currently in Phase II and III for ADHD.
Posted by Mr. Scott on February 3, 2002, at 12:47:28
In reply to I disagree, posted by likewater on February 3, 2002, at 0:22:37
My logic here is flawed, but if Lilly can produce a longer acting Effexor that has tolerability improvements over Effexor, that would be a very good thing for A LOT OF PEOPLE...
Posted by OldSchool on February 3, 2002, at 15:00:31
In reply to Re: Prozac one went south!, posted by djmmm on February 2, 2002, at 23:52:59
"New and improved" Celexa. Meridia for depression. < yawn > < roll eyes >
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 spike4848 on February 3, 2002, at 15:12:49
In reply to Re: New Celexa...BORING!, posted by OldSchool on February 3, 2002, at 15:00:31
> "New and improved" Celexa. Meridia for depression. < yawn > < roll eyes >
> Old School
I have to agree with Old School. I am not to excited about the new Celexa.
Alot of this is marketing by the drug companies .... businesses must alway have a product in the pipeline to stay afloat. Like the Nexium scam ....
Spike
Posted by djmmm on February 3, 2002, at 22:38:35
In reply to Meridia, Atomoxetine, posted by Mr. Scott on February 3, 2002, at 12:43:59
> My understanding is that these are currently in Phase II and III for ADHD.
Meridias r-isomer is in phase 2 for depression and ADHD
Posted by djmmm on February 3, 2002, at 23:43:33
In reply to Re: New Celexa...BORING!, posted by OldSchool on February 3, 2002, at 15:00:31
> "New and improved" Celexa. Meridia for depression. < yawn > < roll eyes >
>
> When is the Selegiline MAOI patch coming out? IS the MAOI patch going to be FDA approved? Now THERE is a real antidepressant!!
>
> Old SchoolMerida sounds interesting to me because the R-isomer has two metabolites r-desmethylsibutramine and r-didesmethylsibutramine which are both potent norepinephrine and dopamine reuptake inhibitors (stimulant qualities).
Posted by Denise528 on February 4, 2002, at 9:02:36
In reply to Re: New Celexa...BORING!, posted by djmmm on February 3, 2002, at 23:43:33
> > Hi,
This Selegiline MAOI patch sounds really good on going by the previous posts. Can somebody explain why?
Thx....Denise
>
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.
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