Psycho-Babble Medication Thread 662854

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Re: couldn't have said it better myself

Posted by linkadge on July 16, 2006, at 18:13:09

In reply to Re: couldn't have said it better myself, posted by SLS on July 16, 2006, at 5:49:59

>Studies using people chosen with more severe >depression have lower placebo response rates.

It is my understaning that severely depressed also respond poorly to active treaments, unless you have data to suggest otherwise.

Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 16, 2006, at 18:44:59

In reply to Re: couldn't have said it better myself » linkadge, posted by SLS on July 16, 2006, at 6:13:38

>You guys are speculating. I think you are both >wrong. I think the degree of placebo response is >dependent on the selection criteria. I have >already cited a paper regarding this issue.

Everybody here has been speculating. You sited a paper that *suggests* this *could* be a reason why placebo responces is high. To proove that this is true is much harder.


>How long do you think they should be followed >for? Is the STAR*D design sufficient?

I'd say that a drug needs to work for a full year to be considered effective, but hey, thats just me.

>Is this speculation? What are the statistics?

Thats a good question. It is my understanding that depression has a high relapse rate.

>Certainly psychotherapy will enhance one's >chances of getting well and remaining well. >There are numbers on this. However, I have not >seen the numbers on relapse rates once >supportive psychotherapy is withdrawn. Let's see >them.

I'd have to look. I guess my best counterargument at this point would be the lack of data showing that antdiepressants work long term.

>That would be considered a placebo effect if you >began to "respond" during the first two weeks >according to some researchers. You might not >really have been responding to the drug. Placebo >responders do not remain in remission for very >long compared to true responders. You can look >at the work of Frederick Quitkin regarding this.

People can relapse too if psychosocial stressors rise above the power of the AD. Perhaps this was the case with me leaving the hospital, and return to a high level of psychosocial stress.

>It was likely neither.

My money is on the bacon.

> It is easy enough to ramp people up to a high dose of antidepressants to get some initial responses, but with the growing information bank regarding AD poop out we could add to the statistics.

>What exactly is that bank? Where can we find >these statistics?

The bank I am referring to, is the increase in awareness that antidepressants can loose their effectiveness over time. Simply typing in "antidepressnant + poop out" in a search engine will return dozens of results. Doctors have been forced to confront the issue, such as in the article below, but I don't know if studies have been conducted. Poop out is a well known phenomina.

http://health.yahoo.com/topic/depression/living/article/pt/psychology_today_articles_pto-19990301-000032

>Cite it. Let us see if they separate out placebo >responders first. If they don't, the statistics >are worthless.

Good point! I would imagine that studies about the issue would be in the works. The problem with things such as this is funding. Drug companies in general, do not want to pay for a study to determine the poop out rate of their drug. In addition, they have no requirement to proove that their drug works long term.


Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 16, 2006, at 18:57:42

In reply to Re: couldn't have said it better myself » linkadge, posted by SLS on July 16, 2006, at 6:41:21

>I believe I've already addressed this issue in >previous posts. I have seen other abstracts on >Medline and elsewhere reporting that clinical >trials of antidepressants using rigid criteria >allowing only the more severe cases of MDD >demonstrate lower placebo response rates and >greater superiority for putative antidepressants.

Oh of course you'll find a few studies that suggest this.

>The following paper describes the failure of >trials with high placebo response rates to >demonstrate superiority of antidepressants, but >not those with low placebo response rates.

Clearly

>It is my contention that high placebo response >rates are indicative of poorly designed >inclusion criteria that allow people who do not >have true MDD to enter the studies.

When you're faced with the fact that overall the antidepressant effect vs. placebo is weak, it becomes natural to want to try and come up with reasons why.

>I feel that
>this is more of a problem today than it was 20 >years ago. I believe this is due to the increase >in monetary pressure to produce subjects for >clinical trials. This is born out by the >steadily increasing rate of placebo response >observed in these studies over the years.

Do you have any data to support this? There are certainly other possable reasons why placebo response may have increased over the years.

Show me data to suggest that increased sevarity of depression has a higher ratio of active treatment to placebo response.

Linkadge

 

Apology - No worries (nm) » SLS

Posted by linkadge on July 16, 2006, at 18:58:25

In reply to Re: couldn't have said it better myself - Apology » linkadge, posted by SLS on July 16, 2006, at 7:23:10

 

Re: couldn't have said it better myself

Posted by linkadge on July 16, 2006, at 19:29:46

In reply to Re: couldn't have said it better myself, posted by SLS on July 16, 2006, at 7:27:45

That study does support your claim, but it is numberless, and difficult to quantify the exact magnitude of discussed claim.

It may be clear that severe depression responds more poorly to placebo but it would be nice to know exactly how significantly the ratio of placebo to active drug changes with increasing sevarity of depression.

I am looking for more studies on this topic.


Linkadge

 

Re: couldn't have said it better myself

Posted by SLS on July 16, 2006, at 19:36:44

In reply to Re: couldn't have said it better myself, posted by linkadge on July 16, 2006, at 19:29:46

> That study does support your claim, but it is numberless, and difficult to quantify the exact magnitude of discussed claim.
>
> It may be clear that severe depression responds more poorly to placebo but it would be nice to know exactly how significantly the ratio of placebo to active drug changes with increasing sevarity of depression.
>
> I am looking for more studies on this topic.


In the good old days, standard response (50% reduction in depression score) was almost invariably:

drug = 70%
placebo = 30%


- Scott

 

Re: couldn't have said it better myself

Posted by SLS on July 16, 2006, at 20:14:10

In reply to Re: couldn't have said it better myself, posted by SLS on July 16, 2006, at 19:36:44

"the placebo response overall appears to have increased over time"

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16181132&query_hl=45&itool=pubmed_docsum


Curr Top Med Chem. 2005;5(11):1077-86.

Is there a placebo problem in antidepressant trials?

Yang H, Cusin C, Fava M.

Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust placebo responses. Meta-analyses of trials in major depressive disorder (MDD) suggest that drug-placebo differences in response rates range from 11% to 18%. However, in trials of marketed antidepressants present in the FDA databases, antidepressant drugs were superior to placebo in only 45 out of 93 RCTs (48%), and the placebo response overall appears to have increased over time. This gradual increase in placebo response rates may lead to delays in bringing new antidepressant treatments to the market, increased costs of antidepressant drug development and, in some cases, decisions to stop the development of certain compounds, or FDA decisions to not approve new treatments. A number of possible contributing factors to this significant placebo response in MDD have been identified, but further studies are needed. Many of the remedies used by researchers to minimize the placebo response, such as lead-in periods or shortening the duration of study visits, have failed to show consistent benefits. From our analysis of published studies, it appears that expectations about the speed of response may be shaped by the duration of the trial and that most of the placebo response occurs in the first half of the trial, regardless of its duration. These observations have led us to develop a novel approach to the placebo response problem called the Sequential Parallel Comparison Design.


- Scott

 

Re: couldn't have said it better myself

Posted by linkadge on July 17, 2006, at 21:26:58

In reply to Re: couldn't have said it better myself, posted by SLS on July 16, 2006, at 19:36:44

>In the good old days, standard response (50% >reduction in depression score) was almost >invariably:

>drug = 70%
>placebo = 30%

Again, I could ask a number of questions.

Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 17, 2006, at 21:32:49

In reply to Re: couldn't have said it better myself, posted by SLS on July 16, 2006, at 20:14:10

"and the placebo response overall appears to have increased over time"

Perhaps, but what magnitide are we talking about. There are no numbers. It could have increased an average of 2% for all I know.

In one sense I can see drug responces in the past as being stronger since the TCA's are more effective drugs.

I would need some numbers that show how the placebo response has increased significantly.

Placebo response could have been lower in the past too due the the weaker "establishement" of AD's in the past.


Linkadge

 

Re: couldn't have said it better myself

Posted by SLS on July 17, 2006, at 22:01:03

In reply to Re: couldn't have said it better myself, posted by linkadge on July 17, 2006, at 21:32:49

> "and the placebo response overall appears to have increased over time"
>
> Perhaps, but what magnitide are we talking about. There are no numbers. It could have increased an average of 2% for all I know.
>
> In one sense I can see drug responces in the past as being stronger since the TCA's are more effective drugs.
>
> I would need some numbers that show how the placebo response has increased significantly.
>
> Placebo response could have been lower in the past too due the the weaker "establishement" of AD's in the past.


The numbers are all there. All you have to do is go to the library and pull out the journals. I started doing that in 1982. That's how I knew the numbers had changed even before I encountered the literature I cited along this thread. I witnessed the changes in placebo response over a 25 year period. It has been far more than 2 percent.

Currently marketed antidepressants work significantly better than our most recent clinical trials indicate.


- Scott

 

Re: couldn't have said it better myself » SLS

Posted by Phillipa on July 17, 2006, at 22:32:42

In reply to Re: couldn't have said it better myself, posted by SLS on July 17, 2006, at 22:01:03

Really Scott you think there's hope for me?. Any suggestions for anxiety with depression anxiety foremost. My pdoc asks me what I want and I have no idea? Love Phillipa

 

Re: couldn't have said it better myself

Posted by SLS on July 17, 2006, at 23:01:41

In reply to Re: couldn't have said it better myself, posted by SLS on July 17, 2006, at 22:01:03

> > "and the placebo response overall appears to have increased over time"
> >
> > Perhaps, but what magnitide are we talking about. There are no numbers. It could have increased an average of 2% for all I know.
> >
> > In one sense I can see drug responces in the past as being stronger since the TCA's are more effective drugs.
> >
> > I would need some numbers that show how the placebo response has increased significantly.
> >
> > Placebo response could have been lower in the past too due the the weaker "establishement" of AD's in the past.
>
>
> The numbers are all there. All you have to do is go to the library and pull out the journals. I started doing that in 1982. That's how I knew the numbers had changed even before I encountered the literature I cited along this thread. I witnessed the changes in placebo response over a 25 year period. It has been far more than 2 percent.
>
> Currently marketed antidepressants work significantly better than our most recent clinical trials indicate.


I know this is going to come as terrible news to you, but there are still doctors who believe that 85% of sufferers of MDD can reach full remission by cleverly using all of the treatments currently available.


- Scott

 

Re: couldn't have said it better myself

Posted by cecilia on July 18, 2006, at 1:52:05

In reply to Re: couldn't have said it better myself, posted by SLS on July 17, 2006, at 23:01:41

Perhaps, but that doesn't really help when you're in the other 15%. Cecilia

 

Re: couldn't have said it better myself

Posted by Klavot on July 18, 2006, at 1:56:43

In reply to Re: couldn't have said it better myself, posted by linkadge on July 16, 2006, at 18:08:54

> I think we are talking about a different study.
>
> This is the one I was thinking of, and yes sertaline did fail in this one.
>
> http://www.herbalgram.org/ogdenpress/herbalgram/articleview.asp?a=2351&p=Y
>
> Linkadge

This *is* the study I am talking about. Again, I would encourage people to read the *actual* paper (freely available at JAMA) rather than rely on second-hand information. The fact that you do not recognise the study mentioned at herbalgram.org as the very 2002 JAMA study I was speaking of just shows how much the findings have been distorted in the popular press.

 

Re: couldn't have said it better myself

Posted by SLS on July 18, 2006, at 6:34:58

In reply to Re: couldn't have said it better myself, posted by cecilia on July 18, 2006, at 1:52:05

> Perhaps, but that doesn't really help when you're in the other 15%.

Nor does it help the 15% to disable the institutions dedicated to discovering ways to treat it.


- Scott

 

Re: couldn't have said it better myself

Posted by Jost on July 18, 2006, at 19:41:23

In reply to Re: couldn't have said it better myself, posted by SLS on July 18, 2006, at 6:34:58

I'm late to this discussion, so maybe this has already been covered, but I have a few questions about the numbers in the Star-d study.

(My math is extremely rusty, so I could be wrong on my numbers-- so I guess I'm offering this with question marks.)

The numbers seem to be as follow:

original number considered for study: 4041
accepted into study: 2876

The first treatment was citalopram (celexa)

Level I

remission 30% (eg approximately 950)
responders 10-15 (eg 287-whatever 15% is) (these people were allowed to to into Level II because they didn't have "remissions" or become "symptom-free"

Ineffective, or too many Side effects to complete 70% (I infer that this number includes the responders, so there were 50-55% with no response, 10-15% with some response)

There were therefore 1914 people eligible to enter Level II.

Note: those who had remissions were to be followed for another 12 months, to evaluate the continuations of their remission, or other outcomes. I didn't notice any mention of them in the later discussion, however, they may be presumed to have some among them who were having a placebo effect, who might need another therapy later, if the study is continuing.

Of the 1914 eligible people, 1439 chose to continue into Level II

This means that almost 500 people dropped out at this point, leaving only 75% of the non-remitters in the study.

These people were given the choice to switch or augment citalopram with another AD. (People opted not to be randomized at this level of the study.)

51% (727) switched to another AD
39% (565) augmented
10% (149) chose to switch or augment with CBT, and were excluded from the final results.

So about 68% of the eligible people, or 1290 people participated in Level II.

Of these 68%, or 1290 people, there were remissions in:

25% of the switchers, or 188 people, and
30% of the augmenters, or 181 people


This means that of the second 1914 eligible, or 1439 participants, 369 had remissions. What 25% and 30% of 68% is, I haven't calculated, but I guess it's between 17-23% (I could be wrong on that...)

Altogether, of the 2876 people who entered level I, 1319 people (or about 46%) had remissions.

On one hand, remission is a higher standard than response, so this could be taken as a positive sign. On the other hand, it means that 64% had some sort of not-entirely-satisfying outcome.

The study, as reported online on the NIMH page, doesn't further divide these into those who had or didn't have a response less than remission, or further detail the quality of the less-than-remission responses. It also doesn't report on the progress of those who had remissions, and what, if any, further and different treatment they might have needed.

Maybe my math is wrong, because it seems to differ from the statistics that SLS quotes, which are more optimistic. If so, I'm interested in how one should analyze the results.

I should also note, however, that there must be some sense among scientists that treatments do work in a way that they take seriously. I say this because there are ethical concerns beginning to be reported about using placebos in studies. This ethical concern is about the use of placebos in patients for whom there is a proven treatment--for whom it is not considered ethically acceptable to give no treatment in a study of potentially helpful drugs.

I personally have had good results with certain ADs, so I'm not in any way debunking their value. I also believe that there are other ADs, which may work better, or other combinations that may work better, than those in the study.

I just wonder about exact outcome of the study, just on the simplest level, in the numbers. (Again, I apologize in advance, if I got this wrong.)

thanks, Jost


 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 19:59:43

In reply to Re: couldn't have said it better myself, posted by SLS on July 17, 2006, at 22:01:03

"Currently marketed antidepressants work significantly better than our most recent clinical trials indicate"

In your opinion. My opinion is that they work significantly worse, seeing as that trial may just be the first one in 10 that shows the drug performed better than placebo. Drug companies do not have to disclose failed drug trials.

Even if the placebo response was to increas slightly, there are still a whole host of miserable drug responces. Its not unheard of to get large trials showing only 35% of people respond to the active drug.

There is an argument too that trial data from 3 decades ago isn't too relyable, this is evidenced by the fact that some of the initial results for the TCA's have been hard to replicate.

I would still argue that antidepressants may produce impressive initial results owing to their ability to quickly reduce REM sleep.

Thats why you get all those accounts of people saying, "the world looked so much brighter".. thats an effect of REM sleep reduction. It usually subsides as the cholinergic system attempts to regain sensitivity.


Linakdge

 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 20:06:15

In reply to Re: couldn't have said it better myself, posted by SLS on July 17, 2006, at 23:01:41

There are also doctors who believe that the drugs work no better than placebo, and that most people recover due to time.

The head doctor, Dr. Powers, I saw at Grand River Hospital, Waterloo, Ontario, Canada, told me that most of the drug effect is placebo.

I don't know if 85% of patients get better as a result of medications. Sometimes patients can try combinations of medications for years. Depression too often gets better on its own. Sometiems people like to attribute their recovery to a drug, but it may not be an appropriate association.

I don't think there is any concrete data to suggest that 85% of depression sufferers get better with meds and combinations.

Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 20:07:37

In reply to Re: couldn't have said it better myself, posted by Klavot on July 18, 2006, at 1:56:43

Well, either zoloft did better than placebo or it didn't.

I think that the primary measures are the ones most likely to be indicitive of drug effect.

Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 20:13:32

In reply to Re: couldn't have said it better myself, posted by SLS on July 18, 2006, at 6:34:58

"Nor does it help the 15% to disable the institutions dedicated to discovering ways to treat it."

I'm not telling people not to try drugs. I wouldn't want to jinx anyone's response. Though, if somebody jinxed my response, I would argue that it wasn't really a response.

I remember I was doing fairly well on clomipramine untill somebody told me that it was genotoxic, and that the cardiac conduction effects could cause heard problems down the road.
Guess, I was never really responding to it in the first place.

My therapist thried the ol'.... "well everything causes cancer these days". Didn't work.


Linkadge

 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 20:32:10

In reply to Re: couldn't have said it better myself, posted by Jost on July 18, 2006, at 19:41:23

>I should also note, however, that there must be >some sense among scientists that treatments do >work in a way that they take seriously. I say >this because there are ethical concerns >beginning to be reported about using placebos in >studies. This ethical concern is about the use >of placebos in patients for whom there is a >proven treatment--for whom it is not considered >ethically acceptable to give no treatment in a >study of potentially helpful drugs.

I would argue that the so called "ethical concerns" are due to the fact that certain researchers wan't the placebo's out of their trials so that people don't end up seeing how well the placebo often performs.

When placebo and active drug are often so neck- and-neck, I see no ethical concerns in using placebo. If you're just as likely to get better on placebo, its not ethically wrong to only use this in your trial.

If your math is right in that 64% of people had inadequate results from antidepressants despite the best possable care, then clearly this is confirming what I know.

We, here on psychobabble are *not* the only ones who don't do so great on these drugs.

Just cause you don't have or know how to use the internet, or don't have the ambition to go online, doesn't mean that your treatment works fine. There are plenty of people who could probably confirm similary modest results but for whatever reason havn't connected. It really depends on what you "want" to see.

Linkadge


 

Re: couldn't have said it better myself

Posted by linkadge on July 18, 2006, at 20:36:54

In reply to Re: couldn't have said it better myself, posted by linkadge on July 18, 2006, at 20:32:10

This summer the result of a study by two psychologists was released in the American Psychological Association's e-journal. This study obtained and reviewed 47 research test studies submitted to the FDA for approval of the most recent antidepressants (Prozac, Paxil, Zoloft, etc). The psychologists found that in judging the effect of a treatment, in terms of how well it does over and above a placebo (sugar pill), the effects of the antidepressants were deemed "clinically negligible".

A second study done by a Seattle psychiatrist, reviewed 96 clinical trials and discovered that in 76% of the cases reviewed the response to antidepressant drugs were duplicated by the placebo. In other words 76% of the time the sugar pill created the same "benefits" that the drug did.

http://www.biohealthinfo.com/html/resources/articles/article_archive/antidepressants.html


Linkadge

 

Re: couldn't have said it better myself

Posted by cecilia on July 18, 2006, at 21:52:38

In reply to Re: couldn't have said it better myself, posted by SLS on July 18, 2006, at 6:34:58

> > Perhaps, but that doesn't really help when you're in the other 15%.
>
> Nor does it help the 15% to disable the institutions dedicated to discovering ways to treat it.
>
>
> - Scott

I certainly would never tell anyone not to try AD's. Certainly if 85% eventually find something that helps that's pretty good. But the remaining 15% is still a huge number of people. A pdoc who sees 100 patients a week will have 15 of them not respond to anything. (Probably a lot more than that, since many people get their 1st and 2nd AD's tried from their GPs and only go to a pdoc if those don't work.) Pdocs certainly don't tell people those odds. You see public service TV commercials "Depression is treatable". They don't say "Depression is treatable unless you're in the unlucky 15%." It makes me angry. Cecilia

 

Re: couldn't have said it better myself

Posted by SLS on July 19, 2006, at 5:31:08

In reply to Re: couldn't have said it better myself, posted by cecilia on July 18, 2006, at 21:52:38

> > > Perhaps, but that doesn't really help when you're in the other 15%.
> >
> > Nor does it help the 15% to disable the institutions dedicated to discovering ways to treat it.
> >
> >
> > - Scott
>
> I certainly would never tell anyone not to try AD's. Certainly if 85% eventually find something that helps that's pretty good. But the remaining 15% is still a huge number of people. A pdoc who sees 100 patients a week will have 15 of them not respond to anything. (Probably a lot more than that, since many people get their 1st and 2nd AD's tried from their GPs and only go to a pdoc if those don't work.) Pdocs certainly don't tell people those odds. You see public service TV commercials "Depression is treatable". They don't say "Depression is treatable unless you're in the unlucky 15%." It makes me angry.

Me too. Me too.

Which tricyclic did you combine with Parnate?


- Scott

 

Re: couldn't have said it better myself

Posted by SLS on July 19, 2006, at 5:57:36

In reply to Re: couldn't have said it better myself, posted by linkadge on July 18, 2006, at 19:59:43

> There is an argument too that trial data from 3 decades ago isn't too relyable, this is evidenced by the fact that some of the initial results for the TCA's have been hard to replicate.

Whose argument would that be?

They already have been.

I thought we already covered this.

All you have to do is thoroughly evaluate the prospects and allow only those with true MDD to participate in studies by including only the more severe cases as scored on standardized depression rating scales - just like was done 20-30 years ago.

One more...

J Psychiatr Res. 2005 Mar;39(2):145-50. Related Articles, Links
Click here to read
Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials.

Khan A, Brodhead AE, Kolts RL, Brown WA.

Northwest Clinical Research Center, Bellevue, MA, USA. akhan@nwcrc.net

Although increased pre-treatment severity of depressive symptoms is thought to suggest better outcome with tricyclic antidepressants, it is unclear if such a pattern exists among those depressed patients treated with newer antidepressants. If such a pattern with newer antidepressants were observed, it would have implications for the design and conduct of future antidepressant trials. We reviewed the data from 329 depressed adult patients that were part of 15 multi-center, randomized, double blind, placebo-controlled antidepressant clinical trials at our center. Based on patients' pre-treatment scores on the 17-item Hamilton Depression Rating Scale (HAM-D), patients were sub-grouped to one of four severity of depression groups: low moderate, high moderate, moderately severe, and severe. The effect size was 0.51 in the low moderate group, 0.54 in the high moderate group, 0.77 in the moderately severe group and 1.09 in the severe group. An analysis of variance revealed a statistically significant interaction between treatment and severity of depressive symptoms. A correlational analysis revealed that in the group of depressed patients assigned to antidepressants, higher levels of pre-treatment depressive symptoms were significantly associated with greater changes in response to antidepressant treatment. Although a similar pattern was seen among the depressed patients assigned to placebo, it did not reach statistical significance. The results of this study suggest that antidepressant-placebo differences may be larger among those depressed outpatients with higher pre-treatment HAM-D scores compared to those depressed outpatients with lower pre-treatment scores. These findings may help in the design of future antidepressant clinical trials.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15589562&query_hl=10&itool=pubmed_docsum


- Scott


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