![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 34 to 58 of 116. Go back in thread:
Posted by JLM on December 14, 2003, at 2:12:14
In reply to Re: Cymbalta/Duloxetine timing, posted by pseudonym on December 13, 2003, at 20:28:35
> There is nothing in that article which contravenes the clinical data for duloxetine.
>
> Also, molecules originally developed for DX A are later found to work for DX B, nothing suspicious there.
>
> I'll get a genuine mea culpa from you yet.
>Well, if it was/IS so much better than fluoxetine, why'd they shelve it in the early 90's? Its been brought back to life, not because its any better, but because fluoxetine is now off patent, and r-fluoxetine was a bomb. A multimillion dollar bomb at that.
Its purely financial, just like Lexapro.
Posted by pseudonym on December 14, 2003, at 3:00:57
In reply to Re: Cymbalta/Duloxetine timing, posted by JLM on December 14, 2003, at 2:12:14
In the 52 week duloxetine study, the baseline HAMD-17 averaged 22.46. By week 52, that average had plummetted to 5.04. Show me any Escitalopram, Citalopram or Fluoxetine study anywhere with that kind of improvement. The financial incentive will always be there (I agree with your point on Lexapro). Have some faith, my friend.
Posted by JLM on December 14, 2003, at 4:13:44
In reply to Re: Cymbalta/Duloxetine timing, posted by pseudonym on December 14, 2003, at 3:00:57
Who conducted the 52 weeks study? Do you have any more details. I'd like to read that.
These types of claims have been made before, for instance with Effexor, and they later proved to be not true.
I don't think one single study is good enough. I'd like to read it, see WHO did (which at this point is more important than ever), and see the methodology.
There was an article in the British press recently that pointed out that about 50 percent of articles are pharmacotherapy are now ghostwritten. Interesting.
Now, the results you have cited may well be valid, I don't know, but that still doesn't answer the question as to why the drug was shelved in the first place, or why they waited for fluoxetine to go off patent, or why they went with r-fluoxetine first, and only pulled this out when it was clear that r-f wasn't going to fly. If the drug is really that supieror to everything else, why wait over a decade to bring it to market? Why not bring
it out in the early 90's and just totally slay your competition?
Posted by pseudonym on December 14, 2003, at 13:18:07
In reply to Re: Cymbalta/Duloxetine timing » pseudonym, posted by JLM on December 14, 2003, at 4:13:44
The article which outlines the 52 week duloxentine study is available in the October 2003 edition of the Journal of Clincal Psychiatry. Furthermore, the same article is also available at http://www.psychiatrist.com/privatepdf/2003/v64n10/v64n1015.pdf.
The site is not freely available, as if often the case with scientific journals, but in the off chance you subscribe, there you go.And as far as a single study is concerned, more exist. There are 6-7 other duloxetine studies available on the site as well.
Posted by lansolut on December 14, 2003, at 19:55:09
In reply to Re: Cymbalta/Duloxetine timing » pseudonym, posted by JLM on December 14, 2003, at 4:13:44
Forget Cymbalta. Watching you guys argue is so entertaining that I've forgotten to be depressed!
> Who conducted the 52 weeks study? Do you have any more details. I'd like to read that.
>
> These types of claims have been made before, for instance with Effexor, and they later proved to be not true.
>
> I don't think one single study is good enough. I'd like to read it, see WHO did (which at this point is more important than ever), and see the methodology.
>
> There was an article in the British press recently that pointed out that about 50 percent of articles are pharmacotherapy are now ghostwritten. Interesting.
>
>
> Now, the results you have cited may well be valid, I don't know, but that still doesn't answer the question as to why the drug was shelved in the first place, or why they waited for fluoxetine to go off patent, or why they went with r-fluoxetine first, and only pulled this out when it was clear that r-f wasn't going to fly. If the drug is really that supieror to everything else, why wait over a decade to bring it to market? Why not bring
> it out in the early 90's and just totally slay your competition?
>
>
Posted by JLM on December 14, 2003, at 20:36:46
In reply to Re: Cymbalta/Duloxetine timing, posted by pseudonym on December 14, 2003, at 13:18:07
Okay, without having read the actual study but just some summaries, am I correct to assume that there was no comparitor substance? IE, no placebo comparison or comparison to an older agent.
If that's the case, then the results really don't mean all that much to me.
Do any of these other studies, ie the 6-7 you mentioned show the same results as the open label study?
Posted by HIBA on December 16, 2003, at 0:36:51
In reply to Re: Cymbalta/Duloxetine timing, posted by JLM on December 14, 2003, at 20:36:46
Hi Guys,Why are you so nervous about cymbalta? What is so special about it? Whenever drug hits the market enthusiam goes high to the everest, only to understand later there is nothing new in it. Go to hell my damned pessimism. But I have learned to be too pessimistic over medications. There is no drug I didn't try in my life. Recently zoloft which helped a bit even in the sexul area. But alas! I am my old self again.
More than fifty years of intensive research hasn't made our depressive's life any better. We are left alone with our sufferings. When one drug helps soon sexual side effects curtain those good effects. An antidepressant without sexual side effects is what we patients need. Will there be any?
HIBA
Posted by JLM on December 16, 2003, at 0:43:34
In reply to Re: What is so special about cymbalta?, posted by HIBA on December 16, 2003, at 0:36:51
HIBA,
I totally can relate to how you feel, trust me. 50 years, and very little real progress has made. That's why I'm skeptical about Cymbalta. I doubt it will be any better than anything we've seen before.
I got some inside info about why it was shelved the first time. It causes urinary retention. In fact, it apparently causes it so well, that its been on the market in Sweden for many years now as a bladder stabilizer.
Wow, Lilly, is that the best you can do?
My sources opinion was, and I quote, "This is Eli Lilly scraping the bottom of the barrel".
Posted by SLS on December 16, 2003, at 8:41:31
In reply to Re: What is so special about cymbalta? » HIBA, posted by JLM on December 16, 2003, at 0:43:34
> My sources opinion was, and I quote, "This is Eli Lilly scraping the bottom of the barrel".One person's bottom of the barrel might be another's cream of the crop.
I've got my fingers crossed that duloxetine comes out sooner than later. As long as it's safe, what would be so terrible if it were to be approved by the FDA? I don't know. Perhaps it would encourage Lilly to sacrifice the R&D of other drugs?
- Scott
Posted by JLM on December 16, 2003, at 8:52:57
In reply to Re: What is so special about cymbalta?, posted by SLS on December 16, 2003, at 8:41:31
Scott, don't you want something that is safe, and effective? Or just safe?
This is interesting too:
http://www.guardian.co.uk/medicine/story/0,11381,1101706,00.html
Posted by SLS on December 16, 2003, at 9:10:09
In reply to Re: What is so special about cymbalta? » SLS, posted by JLM on December 16, 2003, at 8:52:57
> Scott, don't you want something that is safe, and effective? Or just safe?
I want something that is both safe and effective for ME. If duloxetine only helps 25% of people, and I am one of them, that's reason enough for me to want it approved. I don't know why anyone would want to prevent any new drug to be approved unless doing so somehow impacts negatively the development of still newer drugs.
- Scott
Posted by jack smith on December 18, 2003, at 0:45:25
In reply to Re: What is so special about cymbalta? » JLM, posted by SLS on December 16, 2003, at 9:10:09
Scott hit the nail on the head. Everytime something new comes out there are some people that are going to get better when everything else failed. More options is better. PERIOD.
> I want something that is both safe and effective for ME. If duloxetine only helps 25% of people, and I am one of them, that's reason enough for me to want it approved. I don't know why anyone would want to prevent any new drug to be approved unless doing so somehow impacts negatively the development of still newer drugs.
>
>
> - Scott
>
>
Posted by pbjc on December 19, 2003, at 15:47:03
In reply to Re: What is so special about cymbalta? » SLS, posted by JLM on December 16, 2003, at 8:52:57
This site about medical ghostwriting doesn't necessarily demonize the drug companies - they needed willing participants. What about all the unethical doctors that lent their names to articles that they submitted to academic journals when they had done none of the work (the article also hinted that doctors get paid to do this plagiarizing). It takes two parties in this situation - not just the drug companies.
> http://www.guardian.co.uk/medicine/story/0,11381,1101706,00.html
>
Posted by JLM on December 20, 2003, at 7:58:57
In reply to Re: What is so special about cymbalta? » JLM, posted by pbjc on December 19, 2003, at 15:47:03
SLS, that's very true, the docs are culpable.
But, from whence do the articles ORIGINATE? I think that's the more important side of the issue. How can you trust data that comes from a company with a vested interest in their bottom line. At least 'outside' investigators who write their own articles (granted they too are paid to conduct the studies) at least gives somewhat the appearance of objectivity.
Posted by maximum-doser on January 1, 2004, at 18:53:24
In reply to Re: What is so special about cymbalta?, posted by jack smith on December 18, 2003, at 0:45:25
Scott is 100% correct. There is always room for improvement. I've been on anti-depressants since 1985, and have seen tremendous and successive improvements with newer drugs. The manufacturers have done a great job of increasing the efficacy of these drugs, while simultaneously reducing their side-effects.
From my personal experience, Celexa was an improvement over Prozac, and Lexapro was a HUGE improvement over Celexa. Lexapro is not only more effective, I no longer suffer from erectile dysfunction, and that is despite my taking 16 (sixteen) 20 (twenty) milligram tablets per day (a total of 320 mg)!!!
I still don't have total remission, though, which is why I'm always looking forward to trying the latest FDA-approved anti-depressants.
I would venture to say that much of the negativity on this board is from those who have not yet reached full remission. Negativity is a natural component of depression.
Bill
Encino, CA
> Scott hit the nail on the head. Everytime something new comes out there are some people that are going to get better when everything else failed. More options is better. PERIOD.
>
> > I want something that is both safe and effective for ME. If duloxetine only helps 25% of people, and I am one of them, that's reason enough for me to want it approved. I don't know why anyone would want to prevent any new drug to be approved unless doing so somehow impacts negatively the development of still newer drugs.
> >
> >
> > - Scott
Posted by Tom Terrific on January 23, 2004, at 8:22:28
In reply to Re: What is so special about cymbalta? » jack smith, posted by maximum-doser on January 1, 2004, at 18:53:24
Based on the posts below Scott and Bill have not been share with the drug Effexor XR which is a dual mechanism drug for serotonin and norpinephrin and has been around for several years and will have a better side-affect profile than Cymbalta. Lexapro does not normally have a dose response with the normal dose being 20 mg. Lexapro is an isomer of Celexa (basically the same drug) and is no more effective than Celexa. This is proven in THEIR package insert and in clinical trials. They are even being taken to task for false advertising by the European equiv of the FDA. Effexor has clinical trials to back up the fact that they outperform all of the SSRI's: Prozac, Paxil, Zoloft, Celexa, in treating to full remission of symptoms. Bill if you still have residual symptoms, I implore you to ask your doctor about Effexor. Good Luck
Tom
> Scott is 100% correct. There is always room for improvement. I've been on anti-depressants since 1985, and have seen tremendous and successive improvements with newer drugs. The manufacturers have done a great job of increasing the efficacy of these drugs, while simultaneously reducing their side-effects.
>
> From my personal experience, Celexa was an improvement over Prozac, and Lexapro was a HUGE improvement over Celexa. Lexapro is not only more effective, I no longer suffer from erectile dysfunction, and that is despite my taking 16 (sixteen) 20 (twenty) milligram tablets per day (a total of 320 mg)!!!
>
> I still don't have total remission, though, which is why I'm always looking forward to trying the latest FDA-approved anti-depressants.
>
> I would venture to say that much of the negativity on this board is from those who have not yet reached full remission. Negativity is a natural component of depression.
>
> Bill
> Encino, CA
>
>
> > Scott hit the nail on the head. Everytime something new comes out there are some people that are going to get better when everything else failed. More options is better. PERIOD.
> >
> > > I want something that is both safe and effective for ME. If duloxetine only helps 25% of people, and I am one of them, that's reason enough for me to want it approved. I don't know why anyone would want to prevent any new drug to be approved unless doing so somehow impacts negatively the development of still newer drugs.
> > >
> > >
> > > - Scott
Posted by JLM on January 23, 2004, at 8:47:08
In reply to Re: What is so special about cymbalta? » jack smith, posted by maximum-doser on January 1, 2004, at 18:53:24
Once again, I feel I must reiterate a VERY important point:
According to Preskorn, who is well respected, ALL SSRI's have a flat dose response curve. So, that being the case, there is NO medically justifiable reason for anyone taking 320mgs a day. That is just plain excessive. However, the ADVERSE effects are dose dependant.
Are you seeing Ozzy Osbourne's doctor perhaps? ;0
"WHY DOES THE DROPOUT RATE FOR DRUGS WITH A SINGLE MECHANISM OF ACTION INCREASE WITH DOSE ESCALATION?
As a general rule of thumb, excessive engagement of any site of action will cause adverse effects mediated by that site of action without further increasing the magnitude of the desired effect. This appears to happen because the body can no longer compensate for the effect of the drug on that site of action and consequently adverse effects result. Take the SSIs as an example. All members of this class of antidepressants have a flat dose-antidepressant response curve. The usually effective minimum dose of each of these drugs produces 70%-80% inhibition of the serotonin uptake pump using the platelet as a surrogate marker for what is happening in the brain. Although these drugs have a flat dose-antidepressant curve, they have an ascending dose-adverse effects curve, meaning that the incidence and severity of adverse effects of these drugs increase with increasing doses even though antidepressant efficacy does not. These adverse effects include nausea, diarrhea, anxiety, and insomnia. These adverse effects appear to be produced by excessive inhibition of the same site of action that mediates the desired antidepressant response, the serotonin uptake pump."
There it is right there, from one of America's most respected psychopharmocologists.
http://www.preskorn.com/columns/9601.html?print=1
"As Preskorn pointed out, rigorous studies of the SSRIs to one another would be ideal and useful in comparing efficacy and side effects, but no such study exists or is likely to be undertaken. However, that doesn't mean these drugs' outcomes can't be compared.
In his opinion, there's a lot that can be determined based on the large number of SSRI studies that have been done. For example, he noted, the following features have generally been reported as similar across the class:
* Flat-dose antidepressant-response curves -- or the ability to produce the same average response rate at each dose above the effective, minimum dose over the dosing range;
* Equivalent antidepressant action at their usually effective therapeutic dose (however, data for fluvoxamine was not available for comparison);
* Similar efficacy when used on a maintenance basis to prevent relapse;
* The usually effective minimum dose of each produces 60 percent to 80 percent inhibition of seratonin uptake;
* All have benign adverse side effects when compared to drugs in the tricyclic class."I think the last point is starting to be something that is debated thou.
Posted by JLM on January 23, 2004, at 8:50:14
In reply to Re: What is so special about cymbalta?, posted by Tom Terrific on January 23, 2004, at 8:22:28
"Effexor has clinical trials to back up the fact that they outperform all of the SSRI's: Prozac, Paxil, Zoloft, Celexa, in treating to full remission of symptoms."
Ho hum? Are there any INDEPENDANTLY done studies that show that? David Healy seems think that the data was cooked as well. I mean, its a nice claim to make when you're in a highly competitive market, but I don't think its been borne out in the real world. And, in point of fact, a lot of people don't seem to tolerate side-Effexor so well.
Posted by SLS on January 23, 2004, at 9:19:45
In reply to Re: What is so special about cymbalta? » Tom Terrific, posted by JLM on January 23, 2004, at 8:50:14
Many of these studies don't appear to be instituted by drug companies. Of course, I can't be sure. However, Steven Stahl, another well respected psychopharmacologist, believes that Effexor is more effective than SSRIs. The doctors that I have seen recently concur based upon their exeriences with the drug, one of whom is a professor at NYU. But let's not drop names.
Also, you can peruse through these:Effexor, overall, is a good drug in my opinion. It carries some liabilities for producing side effects, but I don't think it is anymore liable than most other available medications.
- Scott
Posted by PoohBear on January 23, 2004, at 18:24:00
In reply to Re: What is so special about cymbalta? » JLM, posted by SLS on January 23, 2004, at 9:19:45
> Effexor, overall, is a good drug in my opinion. It carries some liabilities for producing side effects, but I don't think it is anymore liable than most other available medications.
>
>
> - Scott
I would wholeheartedly concur. It is my belief FROM MY OWN EXPERIENCE, which I admit is limited to a 4 month trial of the drug, that Effexor, though not technically an SSRI, follows the model presented, that effecacy falls off as side effects increase with larger and larger doseages. I only say this because it was my experience. We got it back down to 75mg from 225 (I even tried 300mg one day, WHAT a day!), ramping down in 5 day stages. I've been at 75mg now for 2 months and felt very little in the way of side effects, with the exception of sexual performance, which is not a big deal for me at this time.I feel that Effexor is getting a very bad rap on these boards and that those who've had a positive experience need to speak up. I'm not saying that I won't have withdrawal symptoms at some point in the future if my PDoc and I decide that this isn't the best thing, but I will be prepared for it and do not necessarily EXPECT the worst.
Kind Regards,
Tony
Posted by SLS on January 23, 2004, at 20:34:07
In reply to Re: What is so special about cymbalta? » SLS, posted by PoohBear on January 23, 2004, at 18:24:00
Hey Pooh.> It is my belief FROM MY OWN EXPERIENCE, which I admit is limited to a 4 month trial of the drug, that Effexor, though not technically an SSRI, follows the model presented, that effecacy falls off as side effects increase with larger and larger doseages.
I'm glad that you are doing so well on Effexor.
I would have to say that some people being treated with Effexor do not respond adequately until a dosage of 300-600mg is reached. My own experience would be consistent with this observation as made by the doctors I have worked with. In some cases, my own included, a transient improvement occurs when the dosage of Effexor is lowered quickly. Obviously, the goal is to find the lowest dosage that produces and maintains remission. It would be great if you keep us updated on your progress. One thing that is important to note is that the risk of relapse is significantly greater if an antidepressant is discontinued prior to 9-12 months after remission has been attained.
Good luck!
- Scott
Posted by ditzypixy on January 28, 2004, at 16:00:38
In reply to Re: Cymbalta/Duloxetine timing, posted by lansolut on April 14, 2003, at 19:03:55
does anyone know has cymbalta been released in europe yet? ive read about it and it sounds pretty good.i suppose they all do at first! but id like to try it. i asked my psychiatrist would he prescribe it for me,but he didnt have a clue what i was on about.
Posted by rod on January 28, 2004, at 17:05:15
In reply to has cymbalta been released in europe yet?, posted by ditzypixy on January 28, 2004, at 16:00:38
Posted by JLM on February 12, 2004, at 19:16:13
In reply to Cymbalta/Duloxetine--Something's Up, posted by Jack Smith on March 11, 2003, at 12:55:39
> There has got to be something going on with duloxetine that we just don't know about. I mean they got an approvable letter almost six months ago and knowing Lily's eagerness to get the stuff out, you think it would be here by now. I CANNOT believe that their manufacturing problems are that great. I mean Straterra is here which is also manufactured by Lily. Something is going on. Moreover, apparently Lily is asking for more volunteers to do more clinical trials for depression with cymbalta. I think this drug won't be out for a while, unfortunately. I hope I am wrong.
>
> So many times people get their hopes up. If you look through the archives, you will see posts saying that reboxetine would be out by the end of 1999! Now, we know it's never coming out. Also, you will see posts in 2000 saying that the selegiline patch will be out by the end of that year. Last I heard, someone here talked to Dr. Bodkin who said that he would bet it would be out by this time next year. I would take that bet in a heartbeat. . . . . I have high hopes for cymbalta but looks like I am going to just go with effexor--which seems to be a little less potent than duloxetine and because of its shorter half life almost postively has worse withdrawls.
>
> Just my two cents. Thanks for listening.
>
> JACK
Yes, 'something' is up indeed:"February 12, 2004
Student, 19, in Trial of New Antidepressant Commits Suicide
By GARDINER HARRIS
19-year-old college student who had shown no outward signs of depression killed herself over the weekend at an Eli Lilly & Company laboratory in Indianapolis where she had been participating in a company drug trial for an experimental antidepressant.The student, Traci Johnson, was one of 25 healthy patients at an Eli Lilly clinic who were being given larger than therapeutic doses of duloxetine, which will be known as Cymbalta if it is introduced as an antidepressant. Four days before her death, Ms. Johnson was taken off Cymbalta and given a placebo.
While Eli Lilly asserted that it had properly screened Ms. Johnson before the study started to ensure that she was healthy and had no mental problems, her death is being used by critics of a popular class of antidepressants to bolster their case that the widely used drugs carry the risk of suicidal tendencies for a small number of people, particularly young people.
Four other patients who were given the drug during earlier trials also committed suicide, the company said. The drug is being tested not only as an antidepressant but also as a possible treatment for stress urinary incontinence.
Ms. Johnson's death came less than a week after a federal advisory panel concluded that the Food and Drug Administration should issue stronger warnings to doctors that this class of antidepressants may be linked to suicide and violent behavior in children and teenagers.
A review board has told Eli Lilly to stop entering new patients into the trial, and to have all the current participants evaluated by an independent psychiatrist.
Robert Smith, a Lilly spokesman, said the company did not believe that duloxetine, the drug's generic name, caused the suicide.
"This drug has been studied in 9,000 patients, in depressed and nondepressed healthy people, and we have not been able to discern any signal between duloxetine and suicide or suicidal ideation," Mr. Smith said.
Ms. Johnson had not shown signs of depression, distress or mood swings throughout about a month in the trial, said Dr. Alan Breier, Lilly's chief medical officer.
Patients who abruptly stop therapy with some antidepressants often experience withdrawal symptoms that can include severe agitation, unusual dreams and night sweats. This is especially true of antidepressants like Paxil, made by GlaxoSmithKline, that leave the bloodstream quickly. Cymbalta also leaves the blood stream quickly.
Dr. Breier said Ms. Johnson did not appear to be suffering any withdrawal symptoms. He said the company might never be able to answer why Ms. Johnson killed herself.
"Most people who commit suicide in the general population leave people asking these kinds of questions," Dr. Breier said. "And just because this happens while someone is taking a drug doesn't mean the drug caused it."
Ms. Johnson did not leave a suicide note. She hanged herself in a shower stall Saturday night in the bathroom of Lilly's dormlike laboratory on the top two floors of the Indiana University Medical Center.
She had been attending nearby Indiana Bible College but left school to participate in the study because it paid $150 a day plus meals.
Whether antidepressants cause some people to commit suicide was an issue that flared briefly in the early 1990's but had been largely dismissed by mainstream researchers until last summer. That is when GlaxoSmithKline warned that a series of studies had found that children and teenagers given Paxil were more likely to attempt or think about suicide than those given a placebo.
Wyeth soon followed with a warning suggesting that its antidepressant, Effexor, should not be given to children. British and American drug regulators set to work studying the problem. The British soon concluded that most antidepressants in this class should not be used in children and teenagers since they have not proved effective in that population and could be linked to suicide.
The F.D.A. continues to study the issue, said Susan Cruzan, an agency spokeswoman. The agency is aware of Ms. Johnson's death and will evaluate its implications once the agency receives all of the needed information about it, Ms. Cruzan said."
She was a HEALTHY volunteer in a HEALTHY volunteer study. Hence, they can't use their standard 'it was the illness' arugment this time.
Folks, Lilly shelved this drug a long time ago as a possible AD. It only got brought back to life when r-fluoxetine blew up in their face, and they needed a successor to Prozac to maintain their market share.
Posted by Marilyn on February 17, 2004, at 8:37:21
In reply to Re: Cymbalta/Duloxetine timing, posted by fendleywood on July 19, 2003, at 11:59:42
More information:
http://www.antidepressantsfacts.com/2004-02-07-Traci-Johnson-19-duloxetine.htm
http://www.antidepressantsfacts.com/2004-02-13-FDA-concerned-mother.htm
http://www.antidepressantsfacts.com/Traci-Johnson-duloxetine-FDA.htm
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