![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 39. This is the beginning of the thread.
Posted by SLS on March 1, 2002, at 9:48:21
Hi.
Here's something I thought I'd pass along from Medscape...
1. Duloxetine Significantly Reduces Symptoms of Depression
http://www.medscape.com/viewarticle/411151
From the verbiage used, it appears that duloxetine is similar to venlafaxine, not only with respect to the combined actions of the reuptake inhibition of both NE and 5-HT, but also with respect to efficacy in treating depression. Venlafaxine gets more people well and produces a greater degree of improvement than any of the SSRIs. These conclusions regarding venlafaxine are derived from a study involving over 2000 patients. That duloxetine showed itself to be superior to paroxetine in the studies referred to here indicates that both of these NE/5-HT reuptake inhibitors are superior to the SSRIs. I remember Andrew Nierenberg telling me in 1992 that venlafaxine was sort of a non-MAOI MAOI. Perhaps duloxetine will be as well. I might put off switching to Nardil from Effexor if approval of duloxetine is imminent.Does anyone know how close duloxetine is to reaching market?
- Scott
----------------------------------------------
<excerpts>
"NEW YORK (MedscapeWire) Nov 26 — Data on duloxetine, an
investigational balanced serotonin and norepinephrine reuptake
inhibitor, suggest it is more effective than placebo and paroxetine
in reducing depressive symptoms. In addition, duloxetine was found
to be more effective than placebo in reducing the physical symptoms
associated with depression. The data were presented at the 14th
Annual US Psychiatric and Mental Health Congress in Boston,
Massachusetts.""The studies also suggest that duloxetine provides balanced, potent,
and tolerable effect at all doses, though the therapeutic evidence
of duloxetine 60 mg/once daily dose was similar in magnitude to
duloxetine 40 mg/taken twice a day (80 mg), indicating that a 60
mg/once daily dosing regimen can be used. The data were measured by
mean change on the 17-item Hamilton Depression Rating Scale
(HAMD17).""Duloxetine's dual mechanism of action offers the possibility for
rapid onset of antidepressant effect, better response with pain
symptoms, and higher remission rates than available with SSRIs that
are most commonly prescribed today," said John H. Greist, MD,
clinical professor of psychiatry, University of Wisconsin Medical
School, who presented data on duloxetine at the Congress. "Because
we recognize that serotonin blockade alone is not sufficient for
everyone, and that physical symptoms of depression often go
unresolved, duloxetine may become a potent first-line
antidepressant therapy."
----------------------------------------------
Posted by JohnX2 on March 1, 2002, at 19:03:13
In reply to When is duloxetine to be approved?, posted by SLS on March 1, 2002, at 9:48:21
Hi Scott,I haven't heard much about Duloxetine approval,
but I'll dig around tonight.So what's the status of your Effexor trial? You didn't sound
too upbeat in your earlier post. :(I'm curious what the current thinking is of
your treating physicians? I.E. what rationale
do they have for going direction A vs. direction B ?
Just wondering.I was reading an interesting article in
regards to treatment resistant mood disorders
thinking in terms of my own poop out syndrome:
http://www.acnp.org/g4/GN401000110/Default.htm
It suggested using a calcium channel blocker
such as nimodipine. This blocks calcium flux
through NMDA channels. An nmda antagonist like
memantine would work as well I believe.Btw, have you been reevaluated as a DST
non-suppressor?Sorry I'm so nosy. I'm just curious what the current
indicators are as to why your medicines would not be
kicking in (I'm sure you got me beat on this one).Best Wishes Always,
John> Hi.
>
> Here's something I thought I'd pass along from Medscape...
>
>
>
> 1. Duloxetine Significantly Reduces Symptoms of Depression
>
> http://www.medscape.com/viewarticle/411151
>
>
> From the verbiage used, it appears that duloxetine is similar to venlafaxine, not only with respect to the combined actions of the reuptake inhibition of both NE and 5-HT, but also with respect to efficacy in treating depression. Venlafaxine gets more people well and produces a greater degree of improvement than any of the SSRIs. These conclusions regarding venlafaxine are derived from a study involving over 2000 patients. That duloxetine showed itself to be superior to paroxetine in the studies referred to here indicates that both of these NE/5-HT reuptake inhibitors are superior to the SSRIs. I remember Andrew Nierenberg telling me in 1992 that venlafaxine was sort of a non-MAOI MAOI. Perhaps duloxetine will be as well. I might put off switching to Nardil from Effexor if approval of duloxetine is imminent.
>
> Does anyone know how close duloxetine is to reaching market?
>
>
> - Scott
>
>
> ----------------------------------------------
>
>
> <excerpts>
>
>
> "NEW YORK (MedscapeWire) Nov 26 — Data on duloxetine, an
> investigational balanced serotonin and norepinephrine reuptake
> inhibitor, suggest it is more effective than placebo and paroxetine
> in reducing depressive symptoms. In addition, duloxetine was found
> to be more effective than placebo in reducing the physical symptoms
> associated with depression. The data were presented at the 14th
> Annual US Psychiatric and Mental Health Congress in Boston,
> Massachusetts."
>
> "The studies also suggest that duloxetine provides balanced, potent,
> and tolerable effect at all doses, though the therapeutic evidence
> of duloxetine 60 mg/once daily dose was similar in magnitude to
> duloxetine 40 mg/taken twice a day (80 mg), indicating that a 60
> mg/once daily dosing regimen can be used. The data were measured by
> mean change on the 17-item Hamilton Depression Rating Scale
> (HAMD17)."
>
> "Duloxetine's dual mechanism of action offers the possibility for
> rapid onset of antidepressant effect, better response with pain
> symptoms, and higher remission rates than available with SSRIs that
> are most commonly prescribed today," said John H. Greist, MD,
> clinical professor of psychiatry, University of Wisconsin Medical
> School, who presented data on duloxetine at the Congress. "Because
> we recognize that serotonin blockade alone is not sufficient for
> everyone, and that physical symptoms of depression often go
> unresolved, duloxetine may become a potent first-line
> antidepressant therapy."
>
>
> ----------------------------------------------
Posted by JohnX2 on March 2, 2002, at 2:54:48
In reply to When is duloxetine to be approved?, posted by SLS on March 1, 2002, at 9:48:21
Hi Scott,Have you looked into a nefazodone trial?
Maybe a good augmentation to Effexor before
dumping it.I'm back on Serzone and its fixing my headaches
again. I'm hearing its the best med for PTSD,
which involves a very complex dysregulation of
the HPA axis. Its been the only AD I get a sustainable
response from.Serzone is an interesting medicine to try, not
because it has a statistically less than stellar
track record, but because it is *unique*, i.e.
not another "me too" medicine.I find it interesting because it has a metabolite
that blocks the 5ht-2a receptor and another mCPP
that bangs on the 5ht-2b and 5ht-2c receptor.
So its unique in that it has a post receptor
agonist, and I don't know if you've tried something
like this. Anyways your brain will adjust in
strange ways to an MAOI or SSRI/NRI, but with Serzone
there *always* will be this metabolite banging
away on these post synaptic receptors while
your brain is adjusting to the medicine (changes
in feedback mechanisms can't stop this). This could
cause some new and interesting things to happen
that hopefully can push things in the right
direction. Just a thought.-John
> Hi.
>
> Here's something I thought I'd pass along from Medscape...
>
>
>
> 1. Duloxetine Significantly Reduces Symptoms of Depression
>
> http://www.medscape.com/viewarticle/411151
>
>
> From the verbiage used, it appears that duloxetine is similar to venlafaxine, not only with respect to the combined actions of the reuptake inhibition of both NE and 5-HT, but also with respect to efficacy in treating depression. Venlafaxine gets more people well and produces a greater degree of improvement than any of the SSRIs. These conclusions regarding venlafaxine are derived from a study involving over 2000 patients. That duloxetine showed itself to be superior to paroxetine in the studies referred to here indicates that both of these NE/5-HT reuptake inhibitors are superior to the SSRIs. I remember Andrew Nierenberg telling me in 1992 that venlafaxine was sort of a non-MAOI MAOI. Perhaps duloxetine will be as well. I might put off switching to Nardil from Effexor if approval of duloxetine is imminent.
>
> Does anyone know how close duloxetine is to reaching market?
>
>
> - Scott
>
>
> ----------------------------------------------
>
>
> <excerpts>
>
>
> "NEW YORK (MedscapeWire) Nov 26 — Data on duloxetine, an
> investigational balanced serotonin and norepinephrine reuptake
> inhibitor, suggest it is more effective than placebo and paroxetine
> in reducing depressive symptoms. In addition, duloxetine was found
> to be more effective than placebo in reducing the physical symptoms
> associated with depression. The data were presented at the 14th
> Annual US Psychiatric and Mental Health Congress in Boston,
> Massachusetts."
>
> "The studies also suggest that duloxetine provides balanced, potent,
> and tolerable effect at all doses, though the therapeutic evidence
> of duloxetine 60 mg/once daily dose was similar in magnitude to
> duloxetine 40 mg/taken twice a day (80 mg), indicating that a 60
> mg/once daily dosing regimen can be used. The data were measured by
> mean change on the 17-item Hamilton Depression Rating Scale
> (HAMD17)."
>
> "Duloxetine's dual mechanism of action offers the possibility for
> rapid onset of antidepressant effect, better response with pain
> symptoms, and higher remission rates than available with SSRIs that
> are most commonly prescribed today," said John H. Greist, MD,
> clinical professor of psychiatry, University of Wisconsin Medical
> School, who presented data on duloxetine at the Congress. "Because
> we recognize that serotonin blockade alone is not sufficient for
> everyone, and that physical symptoms of depression often go
> unresolved, duloxetine may become a potent first-line
> antidepressant therapy."
>
>
> ----------------------------------------------
Posted by medlib on March 2, 2002, at 3:27:32
In reply to When is duloxetine to be approved?, posted by SLS on March 1, 2002, at 9:48:21
Hi Scott--
It's great to see you posting again! As you know, I really can identify with not having enough energy or concentration to post; so, no intent to lay a guilt trip, you're just missed. Sorry things have been so rough for you of late--fill us in when you can.
I wouldn't hold my breath waiting for duloxetine. Final approval is being held up by FDA concerns over Lilly's manufacturing quality control. The company failed its most recent reinspection, but it's still projecting final approval in the second half of 2002. Others say "late second half 2002". Reportedly, duloxetine's advantage over Effexor is that it doesn't raise BP. I haven't seen any reports of clinical efficacy for depression superior to Effexor (but I haven't done a thorough search).
Naturally, I could blather on indefinitely, but I've agreed to care for new grandson (my first) in a few hours (8a-6:30p), so I'd better at least *try* for a little sleep. My current rx combo (Effexor, methylphenidate, and Wellbutrin) probably could keep the dead awake--guess I'm about to find out.
More later, if I live that long---medlib
Posted by SLS on March 2, 2002, at 8:46:10
In reply to Re: When is duloxetine to be approved? » SLS, posted by JohnX2 on March 1, 2002, at 19:03:13
Hi John.
Hi Medlib.
> So what's the status of your Effexor trial? You didn't sound
too upbeat in your earlier post. :(Things got to be a mess. I'm pretty sure that Effexor provided some positive effects early on. As I reported them to my doctor, they were significant enough to justify its continuation. Unfortunately, nortriptyline, the tricyclic I chose to add, proved to be confounding. When it exerts an antidepressant effect, the quality of the improvement it produces is the best of the tricyclics I have yet tried (imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, and amoxapine). However, this improvement has been episodic and transient (1/2 to 2 days), and always follows a dosage change, either up or down. It seems that no therapeutic window exists for me. My doctor told me that this situation occurs in as many as twenty percent of people for whom nortriptyline provides some relief. I find that figure extremely large, but I do qualify. Even so, for some reason, he decided to continue with it for over seven months. In retrospect, this was obviously too long. I fault both my doctor and myself for this.
What I decided to do was to ask to switch from nortripyline to imipramine, a drug that has demonstrated a very predictable behavior for me. While still taking 300mg of Effexor, I experienced an extreme worsening of my depression after less than a week of the switch. I couldn't help but to blamed Effexor for this, and decided to discontinue it as it seemed now to be hurting more than helping. Getting off of it was very easy. I have come to discontinue some medications by making dosing "on-the-fly". Although I follow a general schedule of dosage reduction, I simply wait until I begin to feel the onset of withdrawal effects, and dose accordingly. I either nibble off a piece of the original immediate-release tablet or "eyeball" an amount of the pellets of the XR preparation contained within a capsule. I pretty much determine the amount of either by "feel", and judge this according to how I reacted to the previous dosing. Anyway, it worked well enough to get off of 300mg of Effexor within a week's time. One must take into consideration that I remained on a tricyclic throughout this period, and that the NE reuptake inhibition it continued to produce mitigated some of the withdrawal effects from discontinuing Effexor. Regardless, I have used this method successfully with Paxil and various benzodiazepines.
After discontinuing Effexor and experiencing a welcome return of drive and motivation (along with a vocabulary), I decided to revisit nortriptyline. Indeed, there is no single dosage that produces a stable improvement. 75mg is too little and 100mg is too much. Both dosages put my blood-levels within the 50 - 150 therapeutic range. I switched back to imipramine yesterday. At this point, I must entertain the idea of reintroducing Effexor to be sure that I don't mistakenly overlook a successful treatment (Lamictal 300mg; imipramine 200mg - 300mg; Effexor 300mg - 450mg. Perhaps nortriptyline left my system altered in a way that allowed imipramine to produce this effect. I should probably wait to first establish the optimum dosage of imipramine. However, I don't know if I have the patience to do so. I was hoping that duloxetine would be approved very soon so that I could explore it before returning to Effexor or switching to Nardil.
> Btw, have you been reevaluated as a DST
non-suppressor?I am a DST non-suppressor according to tests taken over ten years ago. I don't know of any reason to believe that the older tests were invalid, but I guess it is possible.
> I'm curious what the current thinking is of
your treating physicians? I.E. what rationale
do they have for going direction A vs. direction B ?
Just wondering.Me too.
I think I'll stick with him a while longer - probably through a trial of Nardil. I need to see what cards he's holding in his hand that I haven't seen yet. Perhaps he is not as aggressive and creative to treat someone like me as I was led to believe.
> I was reading an interesting article in
regards to treatment resistant mood disorders
thinking in terms of my own poop out syndrome:
http://www.acnp.org/g4/GN401000110/Default.htm
It suggested using a calcium channel blocker
such as nimodipine. This blocks calcium flux
through NMDA channels. An nmda antagonist like
memantine would work as well I believe.I'll see if I can get through the article. What are its salient points, and how do you interpret them? I'm good for about four or five sentences before my brain gives out. It might take a long time to get through. Here's one for you: I find that if I push myself to read beyond a few paragraphs, my depressed state worsens - not only immediately afterwards, but for the rest of the day. It actually feels as if I completely empty an already empty tank of gas. I always feel guilty for writing posts as long as this one because I know that I wouldn't be able to get through it if I had to read it myself.
> Sorry I'm so nosy.
I'm glad you are, although I perhaps replace the word "nosy" with "concerned". I like to think so, anyway.
> I'm just curious what the current
indicators are as to why your medicines would not be
kicking in (I'm sure you got me beat on this one).I'm not sure I understand the question.
I am still searching for an adequate term to use in place of the word "depression" to be able to accuately portray the nature of affecive disorder as I and many others experience it. As I see it, I suffer from a brain disorder that outwardly and superficially resembles what an otherwise healthy person experiences when they get depressed about something.
> Best Wishes Always,
JohnBack at 'ya.
Oh yeah, I am becoming interested in aripiprazole (Abilitat) as a potential adjunct to antidepressants.
http://www.medscape.com/viewarticle/422878
I have experience a small, but significant when I have added the following atypical APs to antidepressants: olanzapine, risperidone, and ziprasidone. Unfortunately, when I arrive at a dosage that produces an optimal improvement, I also experience unacceptable cognitive side-effects. Dr. Smith believes that this is being caused by DA receptor antagonism rather than antagonism at the 5-TH2 receptor. Hopefully, aripiprazole will not cause these effects because it is a "partial" agonist of DA (dopamine) receptors.
<excerped from the article appearing at Mescape>"Stephen M. Stahl, M.D., Ph.D., Professor of Psychiatry at the
University of California at San Diego, places aripiprazole in the
class of antipsychotics called dopamine system stabilizers (DSSs).
Stahl dubs these new therapeutic agents "Goldilocks" because of
their ability to strike a balance between too much and too little
dopamine. [Editor's Note: The common pharmacologic terminology for
aripiprazole would be a partial dopamine agonist in contrast to
other antipsychotic drugs that are dopamine antagonists. -- SRS]"
- Scott
Posted by Cam W. on March 2, 2002, at 9:31:24
In reply to Re: When is duloxetine to be approved?, posted by SLS on March 2, 2002, at 8:46:10
Scott - I talked to one of the Eli Lilly reps about duloxetine. They expect it to be released in Canada in 2003. Besides depression they are also trying to get approved for some bladder disorder (stress incontinence? - I can't remember).
I have a feeling that it's going to be SSDD (same s**t different day).
- Cam
Posted by Bekka H. on March 2, 2002, at 12:46:17
In reply to Re: When is duloxetine to be approved? » SLS, posted by Cam W. on March 2, 2002, at 9:31:24
> Scott - I talked to one of the Eli Lilly reps about duloxetine. They expect it to be released in Canada in 2003. Besides depression they are also trying to get approved for some bladder disorder (stress incontinence? - I can't remember).
Yes, I've heard that, like many other antidepressants, duloxetine causes urinary retention, so instead of seeing this as a potentially dangerous adverse reaction (it's not healthy to retain your urine), Lilly is trying to capitalize on it and exploit it for marketing purposes.
> I have a feeling that it's going to be SSDD (same s**t different day).
I agree about the SSDD. Just what the world needs -- yet another "me too" lipogenic, impotence-ogenic, wimpogenic SSRI.
Posted by Bob on March 2, 2002, at 14:02:48
In reply to When is duloxetine to be approved?, posted by SLS on March 1, 2002, at 9:48:21
What is expected from Duloxetine that we don't already get from Effexor, except possibly a slightly different response profile? Effexor has many problems for many people, and I don't see how Duloxetine will be any better. I don't doubt that the med will produce robust sexual dysfunction, and weight gain in the long run. It may have a severe withdrawal syndrome like that of Effexor too. Nobody will be able to tell you from a short FDA study, though. Why won't this med me subject to poop-out, like so many of the SSRIs, and Effexor? It seems to me that the medical/pharmaceutical community has not addressed the fact that eventually in many cases, the brain adapts to the drug, and effectiveness is lost. I'm not sure the drug companies care, though, as long as a majority of people respond for appreciable amounts of time. The non-responders can be considered a "difficult minority".
I hate to be negative, but I can't really help it anymore.
Posted by Geezer on March 2, 2002, at 14:30:01
In reply to Re: When is duloxetine to be approved?, posted by Bekka H. on March 2, 2002, at 12:46:17
> > Scott - I talked to one of the Eli Lilly reps about duloxetine. They expect it to be released in Canada in 2003. Besides depression they are also trying to get approved for some bladder disorder (stress incontinence? - I can't remember).
>
> Yes, I've heard that, like many other antidepressants, duloxetine causes urinary retention, so instead of seeing this as a potentially dangerous adverse reaction (it's not healthy to retain your urine), Lilly is trying to capitalize on it and exploit it for marketing purposes.
>
> > I have a feeling that it's going to be SSDD (same s**t different day).
>
> I agree about the SSDD. Just what the world needs -- yet another "me too" lipogenic, impotence-ogenic, wimpogenic SSRI.I called Lilly customer service a couple of months ago. They said they expected US release in late 2002 - understand the FDA is in there messing around with the company computers and recording keeping (standard operating procedure for the FDA Nazis). The only difference between Duloxetine and Effexor I have read about has something to do with a more 50/50 split in the SE NE effect.....apparently you don't have to wade thru as much SE before you get to the NE.
Also was aware Lilly was turning "Lemons Into Lemonade" with the urinary retention hype - another promotional claim has something to do with releiving the physical aches and pains of depression.
Bekka......the "lipogenic, impotence-ogenic, wimpogenic SSRI" almost gave me laughter induced urinary incontinence!
Geezer
Posted by TSA West on March 2, 2002, at 16:38:06
In reply to Re: When is duloxetine to be approved?, posted by SLS on March 2, 2002, at 8:46:10
I'm interested in your trial of amoxapine. How long did you take it and what was your final dose? Did you have any ExtraPyramidal Symptoms?
>>When it exerts an antidepressant effect, the quality of the improvement it produces is the best of the tricyclics I have yet tried (imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, and amoxapine).
Posted by SLS on March 2, 2002, at 17:15:51
In reply to Duloxetine, posted by Bob on March 2, 2002, at 14:02:48
> What is expected from Duloxetine that we don't already get from Effexor, except possibly a slightly different response profile?
I don't know about the rest of the world, but I expect duloxetine to get some people well whom had not previously responded to anything else. I would like to avail myself of the opportunity to try it. Some people have responded to Zoloft whom had not responded to Prozac; Paxil to Zoloft; Celexa to Paxil; Prozac to Celexa etc. Duloxetine might not appear especially novel with respect to monoamine reuptake inhibition in test-tubes, but I'm not sure that anyone understands the brain and actions of psychotropics well enough to draw firm conclusions about a drug's worth based upon what little is assumed to be understood. Laboratory test paradigms using rats are currently more reliable than deduction, although far from infallible.
> Effexor has many problems for many people, and I don't see how Duloxetine will be any better.During a consultation, Patrick McGrath of Columbia-Presbyterian stated to me that for every new drug that appears, a certain percentage of people whom had previously been refractory to treatment responds well to it.
> I hate to be negative, but I can't really help it anymore.
Of course I'm frustrated that there are so few new drugs with novel mechanisms of action available or in development. It's obvious to me that the mechanisms of those that are currently available ain't hitting my target.
How does it hurt me to allow the drug companies and the FDA to release hundreds of drugs that are similar to each other? Capitalism just about insures that drug companies will still be working feverishly to develop novel drugs to break away from the pack. I don't think it is at all negative to be frustrated with the limitations of the current pharmacopeia and want to see drugs with very different mechanisms of action appear. I do, however, think it is negative to prevent drugs of only slightly differing mechanisms of action be brought to market. Slightly different might be different enough for some people. I have a vested interest in seeing duloxetine make it to the pharmacist's shelves. It's one more tool to work with.
- Scott
Posted by Bekka H. on March 2, 2002, at 17:59:05
In reply to Re: When is duloxetine to be approved?, posted by Geezer on March 2, 2002, at 14:30:01
> Bekka......the "lipogenic, impotence-ogenic, wimpogenic SSRI" almost gave me laughter induced urinary incontinence!
> GeezerHello, Geezer, I'm glad I gave you a chuckle. After I posted that, I thought maybe I shouldn't have been so negative because as SLS said, it may help some people, but I'm feeling very discouraged and cynical these days. I'm getting really fed up with pharmaceutical companies, and I think their marketing is a disgrace.
Posted by JohnX2 on March 2, 2002, at 19:45:42
In reply to Re: Duloxetine, posted by SLS on March 2, 2002, at 17:15:51
What do you guys think about the possibility
of this medicine: flibanserin (Ectris)?I've been following it for quite a while.
When I tryed to dig up info from the company,
they wouldn't let me pry anything from there hands,
but I saw they applied for trademark name in the
US at the time (Ectris, this was a year or 2 ago).
Its gotton almost NO marketing hype or fanfare,
its just sorta secretly moved along phase I,II,III
clinical trials.Its not another "me too" medicine. It does something new.
Its a direct acting 5ht-1a agonist combined with a 5ht-2a antagonist
Rumored to be fast acting.-John
> > What is expected from Duloxetine that we don't already get from Effexor, except possibly a slightly different response profile?
>
> I don't know about the rest of the world, but I expect duloxetine to get some people well whom had not previously responded to anything else. I would like to avail myself of the opportunity to try it. Some people have responded to Zoloft whom had not responded to Prozac; Paxil to Zoloft; Celexa to Paxil; Prozac to Celexa etc. Duloxetine might not appear especially novel with respect to monoamine reuptake inhibition in test-tubes, but I'm not sure that anyone understands the brain and actions of psychotropics well enough to draw firm conclusions about a drug's worth based upon what little is assumed to be understood. Laboratory test paradigms using rats are currently more reliable than deduction, although far from infallible.
>
>
> > Effexor has many problems for many people, and I don't see how Duloxetine will be any better.
>
> During a consultation, Patrick McGrath of Columbia-Presbyterian stated to me that for every new drug that appears, a certain percentage of people whom had previously been refractory to treatment responds well to it.
>
> > I hate to be negative, but I can't really help it anymore.
>
> Of course I'm frustrated that there are so few new drugs with novel mechanisms of action available or in development. It's obvious to me that the mechanisms of those that are currently available ain't hitting my target.
>
> How does it hurt me to allow the drug companies and the FDA to release hundreds of drugs that are similar to each other? Capitalism just about insures that drug companies will still be working feverishly to develop novel drugs to break away from the pack. I don't think it is at all negative to be frustrated with the limitations of the current pharmacopeia and want to see drugs with very different mechanisms of action appear. I do, however, think it is negative to prevent drugs of only slightly differing mechanisms of action be brought to market. Slightly different might be different enough for some people. I have a vested interest in seeing duloxetine make it to the pharmacist's shelves. It's one more tool to work with.
>
>
> - Scott
Posted by JohnX2 on March 2, 2002, at 19:55:11
In reply to what do you think of flibanserin (Ectris)?, posted by JohnX2 on March 2, 2002, at 19:45:42
my spelling is so bad. how can I have a college
degree, much less a grade school diploma? sorry for the distraction, it just depresses
me when I re-read my posts and count all my typos.-John
>
> What do you guys think about the possibility
> of this medicine: flibanserin (Ectris)?
>
> I've been following it for quite a while.
> When I tryed to dig up info from the company,
> they wouldn't let me pry anything from there hands,
> but I saw they applied for trademark name in the
> US at the time (Ectris, this was a year or 2 ago).
> Its gotton almost NO marketing hype or fanfare,
> its just sorta secretly moved along phase I,II,III
> clinical trials.
>
> Its not another "me too" medicine. It does something new.
> Its a direct acting 5ht-1a agonist combined with a 5ht-2a antagonist
> Rumored to be fast acting.
>
> -John
>
>
>
>
>
>
> > > What is expected from Duloxetine that we don't already get from Effexor, except possibly a slightly different response profile?
> >
> > I don't know about the rest of the world, but I expect duloxetine to get some people well whom had not previously responded to anything else. I would like to avail myself of the opportunity to try it. Some people have responded to Zoloft whom had not responded to Prozac; Paxil to Zoloft; Celexa to Paxil; Prozac to Celexa etc. Duloxetine might not appear especially novel with respect to monoamine reuptake inhibition in test-tubes, but I'm not sure that anyone understands the brain and actions of psychotropics well enough to draw firm conclusions about a drug's worth based upon what little is assumed to be understood. Laboratory test paradigms using rats are currently more reliable than deduction, although far from infallible.
> >
> >
> > > Effexor has many problems for many people, and I don't see how Duloxetine will be any better.
> >
> > During a consultation, Patrick McGrath of Columbia-Presbyterian stated to me that for every new drug that appears, a certain percentage of people whom had previously been refractory to treatment responds well to it.
> >
> > > I hate to be negative, but I can't really help it anymore.
> >
> > Of course I'm frustrated that there are so few new drugs with novel mechanisms of action available or in development. It's obvious to me that the mechanisms of those that are currently available ain't hitting my target.
> >
> > How does it hurt me to allow the drug companies and the FDA to release hundreds of drugs that are similar to each other? Capitalism just about insures that drug companies will still be working feverishly to develop novel drugs to break away from the pack. I don't think it is at all negative to be frustrated with the limitations of the current pharmacopeia and want to see drugs with very different mechanisms of action appear. I do, however, think it is negative to prevent drugs of only slightly differing mechanisms of action be brought to market. Slightly different might be different enough for some people. I have a vested interest in seeing duloxetine make it to the pharmacist's shelves. It's one more tool to work with.
> >
> >
> > - Scott
Posted by Geezer on March 2, 2002, at 20:14:03
In reply to Re: what do you think of flibanserin (Ectris)? » JohnX2, posted by JohnX2 on March 2, 2002, at 19:55:11
John your spelling was not a problem - mine is worse. Alas, your new drug sent me into hysterics for the second time today. Mind you.....at my age stool softeners are at least as important SSRIs. Think I better get off this thread - I can feel a "redirect" coming.
Geezer
Posted by Geezer on March 2, 2002, at 20:59:06
In reply to Re: When is duloxetine to be approved?, posted by Bekka H. on March 2, 2002, at 17:59:05
> > Bekka......the "lipogenic, impotence-ogenic, wimpogenic SSRI" almost gave me laughter induced urinary incontinence!
> > Geezer
>
> Hello, Geezer, I'm glad I gave you a chuckle. After I posted that, I thought maybe I shouldn't have been so negative because as SLS said, it may help some people, but I'm feeling very discouraged and cynical these days. I'm getting really fed up with pharmaceutical companies, and I think their marketing is a disgrace.Hi Bekka-don't get feeling bad about a comment like that, that's just a "little shootin from the hip". Last Tues. I met with a lady pdoc while in a mixed state (got over-juiced on Remeron), she didn't recognize it, d*** near took her head off when she insisted I needed to undertake cognative therapy. Now that would have been inconsiderate!
Have to agree about the drug companies. Medicine has been commercialized, we are the consumers - we have to be better informed than they are commerical. You keep fighting!
Geezer
Posted by Bob on March 2, 2002, at 21:10:54
In reply to Re: Duloxetine, posted by SLS on March 2, 2002, at 17:15:51
I have no intention of preventing "me too" drugs from hitting the market. I'm just tired of trying drugs. It's almost too much effort now for me to get off one drug and go on another - it's taking too much out of me, and my condition is getting worse and worse. I can't hang my hat on something like duloxetine.
Posted by Bekka H. on March 2, 2002, at 23:47:09
In reply to Re: When is duloxetine to be approved?, posted by Geezer on March 2, 2002, at 20:59:06
Geezer, thank you for the encouragement. By the way, I like your screen name.
Posted by SLS on March 3, 2002, at 12:43:06
In reply to Re: Amoxapine » SLS, posted by TSA West on March 2, 2002, at 16:38:06
Hi TSA.
I tried amoxapine when it first came out in 1982. I don't recall any of the details regarding dosage or length of trial. Sorry. It didn't help at all. In fact, it made my depression worse, particularly with regard to psychomotor-retardation, reduced libido, and a feeling of mental slowing or numbness. I attribute the DA antagonist properties of amoxapine for this.
Your question involving EPS (ExtraPyramidal Symptoms = parkinsonian involuntary movements and akathisia) is a good one. It can be debated as to whether amoxapine should ever been approved as an antidepressant. While working as a research assistant for Baron Shopsin, I investigated the FDA approval process and the ethics practiced by its administrators. In the original trial of 10 subjects, I believe three developed unequivocal EPS. I'd have to go back and find my old notebooks to detail what symptoms developed. Regardless, a 30% incidence of EPS in a trial should have received more focus. It seems that Lederle had a friend in the FDA, for these results were swept under the rug and the approval process allowed to continue.
Amoxapine is derived from the antipsychotic loxapine (Loxitane). Many people would argue that any incidence of EPS is unacceptable in an antidepressant, even if the risk were substantially lower than that of the typical neuroleptic antipsychotics. There were already quite a few effective tricyclics available without the liability of producing EPS and tardive-dyskinesia. However, some people do very well on amoxapine whom had not found success with any of the others. If I were one of those people, I would have quite a different view as to what is unacceptable. I would find it unacceptable to remove amoxapine from the market and applaud everyone who were responsible for it getting there in the first place.
Clomipramine (Anafranil) had at one time been considered the most effective antidepressant available. Although its side effects are generally greater than the other tricyclics, I think its use should be considered in light of your partial response to the others. Clomipramine combines the reuptake inhibitions of both norepinephrine with serotonin. In addition to the anticholinergic side effects common to tricyclics, it can also produce sexual side effects that are similar to those of the SSRIs.
I guess the knee-jerk reaction to your query is, "have you tried an MAOI yet?"
Good luck. It might make sense to first try augmenting amoxapine with things like lithium or Wellbutrin.
- Scott
Posted by SLS on March 3, 2002, at 12:54:07
In reply to Re: Duloxetine » SLS, posted by Bob on March 2, 2002, at 21:10:54
Hi Bob.
> I have no intention of preventing "me too" drugs from hitting the market. I'm just tired of trying drugs. It's almost too much effort now for me to get off one drug and go on another - it's taking too much out of me, and my condition is getting worse and worse.
I know what that's like. I guess we have both been riders on the same train for quite awhile.
> I can't hang my hat on something like duloxetine.
It is sometimes too much to hope. I feel the same way you do. I would rather here that something like a substance-P antagonist were found to be a potent antidepressant.
I hope you find your answer soon.
Sincerely,
Scott
Posted by SLS on March 3, 2002, at 19:33:15
In reply to Re: Duloxetine » Bob, posted by SLS on March 3, 2002, at 12:54:07
Here's a new one (sort of):
http://pharmalicensing.com/news/adisp/982274821_3a8c5305199e4
Excerpts:
"GlaxoSmithKline plc and Merck KGaA have signed a worldwide
development and commercialisation agreement for an antidepressant
with a novel mechanism of action.""The compound, currently known as EMD 68843 or SB 659746-A, is in
Phase II clinical development.""It combines the properties of a selective serotonin- reuptake
inhibitor with those of a 5-HT1A partial agonist."
Does anyone know how long it takes for a drug in phase-II trials to be approved?- Scott
Posted by Bob on March 3, 2002, at 20:50:51
In reply to Re: Duloxetine » Bob, posted by SLS on March 3, 2002, at 12:54:07
> I hope you find your answer soon.
Scott:If you have not found your answer yet, then I hope the same for you.
Bob
Posted by Bob on March 3, 2002, at 21:26:34
In reply to Re: New Glaxo / Merck antidepressant, posted by SLS on March 3, 2002, at 19:33:15
> Here's a new one (sort of):
>
> http://pharmalicensing.com/news/adisp/982274821_3a8c5305199e4
>
> Excerpts:
>
> "GlaxoSmithKline plc and Merck KGaA have signed a worldwide
> development and commercialisation agreement for an antidepressant
> with a novel mechanism of action."
>
> "The compound, currently known as EMD 68843 or SB 659746-A, is in
> Phase II clinical development."
>
> "It combines the properties of a selective serotonin- reuptake
> inhibitor with those of a 5-HT1A partial agonist."
>
>
> Does anyone know how long it takes for a drug in phase-II trials to be approved?
>
> - Scott--------------------------------------------------
Scott:
Forgive me for being obtuse here, but could you explain to me why the drug you described is so unique? What are the advantages of a compound which is an SSRI, yet has a 5HT1A partial agonist property?
Bob
Posted by Ritch on March 3, 2002, at 21:37:46
In reply to Re: New Glaxo / Merck antidepressant, posted by SLS on March 3, 2002, at 19:33:15
> Here's a new one (sort of):
>
> http://pharmalicensing.com/news/adisp/982274821_3a8c5305199e4
>
> Excerpts:
>
> "GlaxoSmithKline plc and Merck KGaA have signed a worldwide
> development and commercialisation agreement for an antidepressant
> with a novel mechanism of action."
>
> "The compound, currently known as EMD 68843 or SB 659746-A, is in
> Phase II clinical development."
>
> "It combines the properties of a selective serotonin- reuptake
> inhibitor with those of a 5-HT1A partial agonist."
>
>
> Does anyone know how long it takes for a drug in phase-II trials to be approved?
>
> - Scott
Gee Scott,That sounds an awful lot like combining Celexa+Buspar. I tried that before and it *did* work fairly well. Maybe others ought to consider that combination in the mean time? Of course, Buspar is relatively "dirty" given its DA receptor affinities, metabolites, etc.
Mitch
Posted by JohnX2 on March 3, 2002, at 23:09:10
In reply to Re: New Glaxo / Merck antidepressant, posted by SLS on March 3, 2002, at 19:33:15
Everything I read about pharmacology of
serotonergic systems seems to indicate that
you want to have an agonist at the 5ht-1a site
while antagonizing or down regulating the 5ht-2a site.Its believed from what I understand that a lot of SSRIs dont
respond because either they don't make it through
the first pass of downregulating the somotodendric
5ht-1a autorecptors (which would then increase
serotonin release, which pindolol is believed
to work at), or the medicine has difficulty
downregulating the postsynaptic receptors.Most SSRIS overtime downregulate 5ht-2 receptors
From "Essential Psychopharmacology" by Stephen
M. Stahl, 2nd edition. (a good book)
Figure 7-19
"Molecular stimulation of the 5ht-2a receptor
will alter the consequence of activating the
serotonin 5ht-1a receptor in a negative way and
reduce the gene expression of the 5ht-1a receptor
acting alone.....blah blah"Figure 7-21
Synergy between 5ht-1a stimulation and 5ht-2a
antagonism:
"The molecular consequence of 5ht-1a receptor
by disinhibition by 5ht-2a blockade is shown here,
namely enhanced gene expression...."So to beat around the bush, Stahl is suggesting
make a direct acting 5ht-1a agonist and combine
it with a 5ht-2a antagonist. i.e. something
like flibanserin. Maybe you can combine it
with a el-cheapo off patent SSRI to get an
enhanced effect.-John
> Here's a new one (sort of):
>
> http://pharmalicensing.com/news/adisp/982274821_3a8c5305199e4
>
> Excerpts:
>
> "GlaxoSmithKline plc and Merck KGaA have signed a worldwide
> development and commercialisation agreement for an antidepressant
> with a novel mechanism of action."
>
> "The compound, currently known as EMD 68843 or SB 659746-A, is in
> Phase II clinical development."
>
> "It combines the properties of a selective serotonin- reuptake
> inhibitor with those of a 5-HT1A partial agonist."
>
>
> Does anyone know how long it takes for a drug in phase-II trials to be approved?
>
> - Scott
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