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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by SLS on July 17, 2003, at 11:14:24
Sibutramine (Meridia) is a potent reuptake inhibitor of serotonin, norepinephrine, and to a lesser extent, dopamine. It sounds like it should make a good antidepressant. That is what it was originally developed as, but later got approved for obesity.
Has anyone tried sibutramine?
Thanks.
- Scott
Posted by jrbecker on July 17, 2003, at 11:34:46
In reply to Anybody try SIBUTRAMINE (Meridia) for depression?, posted by SLS on July 17, 2003, at 11:14:24
I know there has been some trials of it for depression, but am not aware of any of the results.
However, I do know that Sepracor is in Phase II trials for a sibutramine metabolite for depression, but is currently on hold due to budgetary constraints.
Posted by SLS on July 17, 2003, at 11:49:55
In reply to Re: Anybody try SIBUTRAMINE (Meridia) for depression?, posted by jrbecker on July 17, 2003, at 11:34:46
> However, I do know that Sepracor is in Phase II trials for a sibutramine metabolite for depression, but is currently on hold due to budgetary constraints.
Hi JB.
Thanks for the heads-up. I found the following:
"Sepracor's (R)-sibutramine metabolite is an isomer of an active metabolite of Abbott's MERIDIA®. The (R)-sibutramine metabolite has been shown in preclinical studies to be a potent norepinephrine, dopamine and serotonin reuptake inhibitor. The compound's unique triple mechanism of action may provide a broader spectrum of therapy than other currently marketed antidepressants. Physicians often prescribe various combinations of drugs to achieve similar outcomes, indicating a need for this potential therapeutic synergy."
This sounds great.
"The (R)-sibutramine metabolite development program for refractory depression is on budgetary hold due to resource constraints."
This sounds not-so-great.
Are you aware of any DA reuptake inhibitors in the R&D pipeline? Nomifensine helped a great many people before it was discontinued.
What's your take on the sibutramine controversy? Do you think the FDA will pull the drug from market?
- Scott
Posted by jrbecker on July 17, 2003, at 13:55:24
In reply to Re: Anybody try SIBUTRAMINE (Meridia) for depression?, posted by SLS on July 17, 2003, at 11:49:55
I have followed very little of the Meridia controversy since last year. I think a lot of people predicted an FDA ruling by the end of '02, but that never happened. Honestly, there are so many law suits and warnings issued for currently marketed prescription drugs that it's hard to cut through the b.s. of which ones are really harmful and which ones are just victims of media hype/litigation hounding. To my own knowledge, I haven't seen anything recently that would foreshadow a recall in the very near future.
As for other DA agonists in the pipeline, it all depends on what you mean. Are you talking strictly for depression or for other indications as well? Because I know there are plenty of different compounds being tested for Alz, parkinson's, ADHD, and the like. I really don't keep up with them because, selfishly speaking, I really don't believe DA agonists are optimal therapies for my kind of depression.
But in regards, to what DA-activating drugs (not just DA agonists) are being tested specifically for depression, there is:
EmSam (transdermal selegiline), an MAO-inhibitor
Somerset for severe Depression, in phase III
KW-6002, an A2A antagonist, by Kyowa Hakko, for Parkinson's/depression, in Phase IIDOV 216,303, a DA/NE/5HT reuptake inhibitor, for depression, by DOV pharm., in Phase II
(R)-sibutramine metabolite, a DA/NE reuptake inhibitor, by Sepracor, in Phase II
GW353162, a DA/NE reuptake inhibitor, Depression and Bipolar Disorder, GlaxoSmithKline, in Phase I
VR 2006, an adenosine receptor atag., Vernalis,
Phase IDOV 21, 947, a DA/NE/5HT reuptake inhibitor, for depression, by DOV pharm., in Phase II
*This list fails to encompass drugs that will indirectly activate DA release (e.g., Cymbalta, OFC-1453, Agomelatine, etc.)
**And I'm sure there are many more DA agonists in trials for neurdegenerative diseased in late stage trials that will capitalize on the success of Mirapex and Requip, so perhaps there will be some success in off-label usage for affective conditions as well.
For more, on current clinical trial compounds, see my rough list at:
http://www.geocities.com/jrbecker76/jrbecker76.htm
> > However, I do know that Sepracor is in Phase II trials for a sibutramine metabolite for depression, but is currently on hold due to budgetary constraints.
>
> Hi JB.
>
> Thanks for the heads-up. I found the following:
>
> "Sepracor's (R)-sibutramine metabolite is an isomer of an active metabolite of Abbott's MERIDIA®. The (R)-sibutramine metabolite has been shown in preclinical studies to be a potent norepinephrine, dopamine and serotonin reuptake inhibitor. The compound's unique triple mechanism of action may provide a broader spectrum of therapy than other currently marketed antidepressants. Physicians often prescribe various combinations of drugs to achieve similar outcomes, indicating a need for this potential therapeutic synergy."
>
> This sounds great.
>
> "The (R)-sibutramine metabolite development program for refractory depression is on budgetary hold due to resource constraints."
>
> This sounds not-so-great.
>
> Are you aware of any DA reuptake inhibitors in the R&D pipeline? Nomifensine helped a great many people before it was discontinued.
>
> What's your take on the sibutramine controversy? Do you think the FDA will pull the drug from market?
>
>
> - Scott
>
Posted by Jack Smith on July 17, 2003, at 15:28:35
In reply to Re: Anybody try SIBUTRAMINE (Meridia) for depression? » SLS, posted by jrbecker on July 17, 2003, at 13:55:24
> IHonestly, there are so many law suits and warnings issued for currently marketed prescription drugs that it's hard to cut through the b.s. of which ones are really harmful and which ones are just victims of media hype/litigation hounding.
Although it cannot be doubted that some drugs are really harmful, I feel that media hype and litigation hounding have become more harmful for those of us seeking effective treatments. Check this link out:
http://www.injuryboard.com/view.cfm/ID=752
Pregabalin is not even approved yet and there is already a site just waiting for people to sue. Crazy.
On another note, is NK-1 the same thing as substance P? Pardon my ignorance. And is Pagaclone the anxiolytic people were talking about that was not going to have drowsiness as a side effect?
Thanks,
JACK
Posted by ProzacPuppet on July 18, 2003, at 9:20:07
In reply to Anybody try SIBUTRAMINE (Meridia) for depression?, posted by SLS on July 17, 2003, at 11:14:24
Hey,
I think like someone mentioned in another post, about something similar, the reason WHY Meridia may work for depression is because Meridia and other anti obesity drugs like it (phentermine, tenute, adipex,) work like an amphetamine. They control the part of the nervous system and brain that controls appetite and they can over stimulate norepinperhine and dopamine levels that in turn can cause a lot of people taking them insomnia. But the most important thing to know here is that Meridia and it's cousin drugs, are for short term use for obesity, not long term use for depression. And they probably are only meant to be used for short term use because of the amphetamine effect they have, which could lead to addiction and also lots of other horrible side effects.
Posted by SLS on July 18, 2003, at 9:48:38
In reply to Re: Anybody try SIBUTRAMINE (Meridia) for depressi, posted by ProzacPuppet on July 18, 2003, at 9:20:07
Hi PP.
> I think like someone mentioned in another post, about something similar, the reason WHY Meridia may work for depression is because Meridia and other anti obesity drugs like it (phentermine, tenute, adipex,) work like an amphetamine. They control the part of the nervous system and brain that controls appetite and they can over stimulate norepinperhine and dopamine levels that in turn can cause a lot of people taking them insomnia. But the most important thing to know here is that Meridia and it's cousin drugs, are for short term use for obesity, not long term use for depression. And they probably are only meant to be used for short term use because of the amphetamine effect they have, which could lead to addiction and also lots of other horrible side effects.
I don't know to what extent sibutramine resembles amphetamine with regard to psychostimulant effects. It might not at all. I don't know. However, that sibutramine has been approved by the FDA for the treatment of obesity does not indicate that it is not safe and effective for any other medical condition. An example of this would be Depakote (valproate). It was used effectively as a mood stabilizer and anti-manic agent for over a decade before the FDA approved it for use in bipolar disorder. Although I haven't researched sibutramine sufficiently to commit to trying it, I haven't yet come across anything that would disuade me from doing so.
- Scott
Posted by jrbecker on July 18, 2003, at 10:41:55
In reply to Re: Anybody try SIBUTRAMINE (Meridia) for depressi, posted by Jack Smith on July 17, 2003, at 15:28:35
> Although it cannot be doubted that some drugs are really harmful, I feel that media hype and litigation hounding have become more harmful for those of us seeking effective treatments. Check this link out:
>
> http://www.injuryboard.com/view.cfm/ID=752unbelievable
> Pregabalin is not even approved yet and there is already a site just waiting for people to sue. Crazy.
>
> On another note, is NK-1 the same thing as substance P? Pardon my ignorance. And is Pagaclone the anxiolytic people were talking about that was not going to have drowsiness as a side effect?Yes, NK-1 antagonists work on substance P - and are considered the same thing. There are also NK-2 and NK-3 antagonists in the works for other conditions beside affective disorders. And yes, Pagoclone [by Indevus] is considered to be a newer anxiolytic since it acts as an agonist at certain subtypes of the GABA-A receptor, so it causes less sedation/memory probs. The efficacy of the clincal studies were mixed though, and many major pharm. companies have passed on helping Indevus make it to market. Right now, there has been no movement on it. Ocinaplon [by DOV] is like pagoclone, but has done a lot better in testing thus far. It is entering Phase III trials next month, but will not be on the market for at least two whole years.
The main reasons why these newer, better side-effect profile anxiolytics haven't come to the market earlier are: 1) SSRIs and other newer AD classes have done a fair job of treating anxiety in most cases, and 2) these newer anxioytics are for very specific anxiety (e.g., GAD, panic disorder). Despite benzos being one of the best selling drug classes, they have been edged out by other categories like ADs and sleep aids. Xanax and Klonopin used to be prescribed a lot more liberally for not just anxiety but also sleep. Now that is not the case. In the end, big pharm companies are looking for drugs that can treat more than just one condition. Take pregabalin for instance. Not a particularly great anxiety drug on its own (cumbersome side effects at higer doses, questionable efficacy when stacked up against other anx drug profiles) but it's going to treat a number of conditions: epilepsy, panic disorder, GAD, bipolar?, etc. This is why a drug like this makes it to market faster than pagoclone does. Just like so many other things in life, it's sometimes just good business.
by the way, how's that xanax xr working? It's been years since I tried regular xanax, I always found it too numbing -- mostly just used it for sleep. preferred klonopin or ativan, personally. My doc called in a xanax xr script, but I haven't bothered picking it up at the pharmacy since I thought it won't be to my liking (I stay away from most benzo's anyway since they just make me tired). what's your input? is xanax xr a much better drug or is it just a slight tweak on the orginal form?
JB
Posted by River1924 on July 21, 2003, at 0:34:15
In reply to Anybody try SIBUTRAMINE (Meridia) for depression?, posted by SLS on July 17, 2003, at 11:14:24
Yes, it works okay for depression. But, for me, it causes a lot of anxiety. I use it in the winter when I tend to need a very stimuling medication for depression. More stimulating that ritalin. I can get out of bed when the alarm sounds...for someone who is half-comatose in the morning, sibutramine is miraculous. I also use it if I need to get off Effexor. I switch from one to the other overnight, use it for a week or 10 days and avoid the weeks of withdrawal from effexor. Hope that helps a little.
Posted by Jack Smith on July 21, 2003, at 17:26:53
In reply to Re: » Jack Smith, posted by jrbecker on July 18, 2003, at 10:41:55
> > http://www.injuryboard.com/view.cfm/ID=752
>
> unbelievable
>Isn't that crazy?
> Yes, NK-1 antagonists work on substance P - and are considered the same thing.Do you have any clue when some of these may be available for depression? I understand that the one now available for chemotherapy-induced nausea is priced extremely high and may be giving the company an incentive to hold its approval for depression.
> Right now, there has been no movement on it. Ocinaplon [by DOV] is like pagoclone, but has done a lot better in testing thus far. It is entering Phase III trials next month, but will not be on the market for at least two whole years.
>At least. That sucks.
> Take pregabalin for instance. Not a particularly great anxiety drug on its own (cumbersome side effects at higer doses, questionable efficacy when stacked up against other anx drug profiles)
So, I take it you don't believe the pregabalin hype? Do you think its efficacy will be similar to neurontin given that it seems to be a modified version of neurontin.
> is xanax xr a much better drug or is it just a slight tweak on the orginal form?
>I'd say it's a slight, but significant tweak on the original form. I think if you didn't like xanax in the first place, you probably wouldn't like the xr. One big thing for me is there is no crash that I used to get from regular xanax. It seems a little less sedating and has a more subtle effect. I have not however decided to use it daily yet. I may in the future. Just not sure I want to go down that road yet, though I definitely get a noticable AD effect.
JACK
Posted by jrbecker on July 23, 2003, at 11:43:30
In reply to JR Becker, posted by Jack Smith on July 21, 2003, at 17:26:53
> > Yes, NK-1 antagonists work on substance P - and are considered the same thing.
> Do you have any clue when some of these may be available for depression? I understand that the one now available for chemotherapy-induced nausea is priced extremely high and may be giving the company an incentive to hold its approval for depression.I doubt they have an incentive to hold their drug up any further. Remember, depression sufferers are a much larger population than those undergoing chemo. Getting as many indication approvals as possible spells $$$.
Merck's drug will probably be the first to hit the market, but that won't be until late '04 -- they're still wrapping up phase III. There are many other companies in tow in phase I and II. If this class proves to be lucrative (which is currently anybody's guess), we can expect to see many of these start to enter the market in '05 and '06.
> So, I take it you don't believe the pregabalin hype? Do you think its efficacy will be similar to neurontin given that it seems to be a modified version of neurontin.Pregabalin will be an improvement on neurontin. Pfizer is smart enough to know what it has or it wouldn't have pushed it this far as Neurontin's successor. And it will make a fair anxiolytic, better than neurontin most likely. However, there will be some side effects involved, much like neurontin's.
>Xanax XR:
> I'd say it's a slight, but significant tweak on the original form. I think if you didn't like xanax in the first place, you probably wouldn't like the xr. One big thing for me is there is no crash that I used to get from regular xanax. It seems a little less sedating and has a more subtle effect. I have not however decided to use it daily yet. I may in the future. Just not sure I want to go down that road yet, though I definitely get a noticable AD effect.thanks for the info. I think I plan on holding off in trying it for a while.
JB
Posted by jrbecker on July 25, 2003, at 13:54:40
In reply to Re: » Jack Smith, posted by jrbecker on July 23, 2003, at 11:43:30
Oh, I forgot to mention that Pfizer will submit an NDA for pregablin probably around 4Q of this year for the indications of general anxiety disorder as well as epilepsy and neuropathic pain.
This is the end of the thread.
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