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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 17 to 41 of 41. Go back in thread:
Posted by bassman on July 13, 2006, at 16:32:50
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by qbsbrown on July 13, 2006, at 14:29:27
Yes, I'm serious and it is very well known and very embarassing to drug companies. Check it out on the web or if you'd like me to dig up some references to depress you, I will. Recently there was a journal article ref on this board where Celexa was compared to Lexapro and neither were better than placebo, many others...
My theory on why that is (which is worth about 2 cents) is that clinical trials last, say, 8 weeks. During that period, there is a significant number of people that go into remission spontaneously. That makes the math messy: if 50% of the people went into remission of their own accord and the AD was effective for 30% of the people, then the statistics, without error, would be placebo 50%, AD 65%. But there is always a large error in any study involving creatures and 10% error would be great. So the results could look like 55% for placebo to 59% for AD easily. You get the idea: the only way you can get a really good number is to make the placebo group promise they won't get better. :>}
As you can imagine, the anti-AD folks have a picnic with the "no difference between AD and placebo" studies, of which there are many. Oh, check the package insert for any AD you might have and see if you are inpressed with how well the AD did clinically. :>}
Posted by SLS on July 13, 2006, at 18:06:03
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 13, 2006, at 16:32:50
> My theory on why that is (which is worth about 2 cents) is that clinical trials last, say, 8 weeks. During that period, there is a significant number of people that go into remission spontaneously. That makes the math messy: if 50% of the people went into remission of their own accord and the AD was effective for 30% of the people, then the statistics, without error, would be placebo 50%, AD 65%. But there is always a large error in any study involving creatures and 10% error would be great. So the results could look like 55% for placebo to 59% for AD easily. You get the idea:
I think it is quite a bit more complicated than that.
I wish I were a mathematician.
In most studies, I believe the placebo response is about 30%. That is unacceptably high. I think it needs to be brought down.
Among other things, I believe the inclusion criteria for these studies allows people in who do not have a biologically-driven mental illness. I think we need to define more rigidly what it is we are setting out to treat. I think people with 100% psychological depressions are apt to feel less depressed on a placebo if they believe they are to be helped by it. Even properly-screened people with biological depressions entering the NIMH report feeling better during the first two weeks of their admission because they are so relieved that they are to finally be cured of their illness. These people are given a placebo run-in during this period. If these people with biological depressions report feeling better, even though they really aren't, are our testing implements valid when they rely so heavily on self-reporting? I also think people with psychogenic depressions are far less apt to respond to a somatic treatments like antidepressant therapy. Sure, some of the placebo responders are biogenic spontaneous remitters, but I believe a great many of them, perhaps the majority, are psychogenic remitters. Placebo responders are too high because the number of psychogenic depressives susceptible to suggestion is too high. Active compound responders are too low because psychogenic non-responders are too high. We must more rigidly and narrowly define the illnesses we are investigating and more rigorously select our subjects for our treatment studies to obtain any meaningful results.
If we are going to treat anything that looks grossly like depression with a single class of treatments, we will fail miserably. We will have greater success once we are able to more finely differentiate between the presentations of the various syndromes.
I know this introduction represents to a great degree black-or-white thinking regarding depression as a psychobiological phenomenon. However, it does serve to underscore the reality that there is no standardization of selection criteria for clinical trials for antidepressants or even a definition of what depression is.
These drugs work. We see that this is true with our own eyes, just as we do the sun shining. There must therefore be a problem with the testing.
Oh, yeah. I almost forgot. These drugs suck. They don't work for everyone all of the time. They don't work for me. If you are reading this, they probably don't work for you. Even when they do work, they have side effects. Often, they stop working after some period of time, and you have to look for another one. A lot of times, you have to endure withdrawal syndromes when you discontinue them. They are expensive. The drug companies are taking advantage of us and are concerned only with their profit margins. Etc.
- Scott
Posted by SLS on July 13, 2006, at 19:04:11
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by SLS on July 13, 2006, at 18:06:03
> In most studies, I believe the placebo response is about 30%.
This number keeps creeping higher and higher it seems.
- Scott
Posted by bassman on July 14, 2006, at 5:49:02
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by qbsbrown on July 13, 2006, at 14:29:27
This is an interesting general article on antidepressants that mentions that about 50% of all clincial trails don't show any difference between AD and placebo. The opening paragraphs story is very interesting, too.
http://www.motherjones.com/news/feature/2003/11/ma_565_01.html
Posted by bassman on July 14, 2006, at 6:55:47
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 14, 2006, at 5:49:02
Just another point of view:
Escitalopram: superior to citalopram or a chiral chimera?
Psychother Psychosom 2004 Jan-Feb;73(1):10-6 (ISSN: 0033-3190)
Svensson S; Mansfield PR
Department of Clinical Pharmacology, Sahlgren's University Hospital, Gothenburg, Sweden Healthy Skepticism Inc., Willunga, Australia. staffan.svensson@pharm.gu.se.BACKGROUND: Escitalopram is the active isomer of the antidepressant citalopram. In theory single-isomer drugs may be superior but few have been found to have clinically significant advantages. The manufacturer claims that escitalopram has more efficacy and a faster onset of effect than citalopram. The purpose of this study was to assess how far these claims are justified.
METHODS: Relevant trial reports were requested from H. Lundbeck A/S and the Swedish drug regulatory authority. The trials consisted of a pooled analysis of 1,321 patients from one unpublished, one partly published and one published eight-week trial, as well as a 24-week trial with 357 patients published as a poster. The studies compared escitalopram with placebo and/or citalopram in outpatients aged or=18 years who met specified criteria for depression. The trials' quality was assessed with Moncrieff et al.'s quality assessment instrument and the results compared with the claims from the advertisements.
RESULTS: The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices. CONCLUSIONS: On the evidence available to us the manufacturer's claims of superiority for escitalopram over citalopram are unwarranted. The Swedish and Danish drug regulatory authorities reached similar conclusions. This highlights the need for wider dissemination of national authorities' statements to other countries affected by the European Union's mutual recognition procedure. [Copyright 2004 S. Karger AG, Basel].
Posted by SLS on July 14, 2006, at 7:29:52
In reply to Study sees no difference between Lex and Celexa, posted by bassman on July 14, 2006, at 6:55:47
I've tried Lexapro, but not Celexa. Right now, Lexapro is my doctor's SSRI of choice. It did nothing for me. The only other SSRI I haven't tried is Luvox. There have been people here who report responding better to Celexa than to Lexapro. Sometimes different is different enough. So much for in vitro experiments and theories.
You know, it occurs to me that there will probably never be another SSRI to be brought to market in our lifetimes. I find this sad. There have to be better ones floating around in test tubes somewhere.
- Scott
> Just another point of view:
>
> Escitalopram: superior to citalopram or a chiral chimera?
>
> Psychother Psychosom 2004 Jan-Feb;73(1):10-6 (ISSN: 0033-3190)
> Svensson S; Mansfield PR
> Department of Clinical Pharmacology, Sahlgren's University Hospital, Gothenburg, Sweden Healthy Skepticism Inc., Willunga, Australia. staffan.svensson@pharm.gu.se.
>
> BACKGROUND: Escitalopram is the active isomer of the antidepressant citalopram. In theory single-isomer drugs may be superior but few have been found to have clinically significant advantages. The manufacturer claims that escitalopram has more efficacy and a faster onset of effect than citalopram. The purpose of this study was to assess how far these claims are justified.
>
> METHODS: Relevant trial reports were requested from H. Lundbeck A/S and the Swedish drug regulatory authority. The trials consisted of a pooled analysis of 1,321 patients from one unpublished, one partly published and one published eight-week trial, as well as a 24-week trial with 357 patients published as a poster. The studies compared escitalopram with placebo and/or citalopram in outpatients aged or=18 years who met specified criteria for depression. The trials' quality was assessed with Moncrieff et al.'s quality assessment instrument and the results compared with the claims from the advertisements.
>
> RESULTS: The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices. CONCLUSIONS: On the evidence available to us the manufacturer's claims of superiority for escitalopram over citalopram are unwarranted. The Swedish and Danish drug regulatory authorities reached similar conclusions. This highlights the need for wider dissemination of national authorities' statements to other countries affected by the European Union's mutual recognition procedure. [Copyright 2004 S. Karger AG, Basel].
Posted by bassman on July 14, 2006, at 7:55:24
In reply to Re: Study sees no difference between Lex and Celex, posted by SLS on July 14, 2006, at 7:29:52
Scott, wow, I never thought of that! I do hope you are wrong (for a change)-I have this hope that someone is going to make an AD that works very well and doesn't have a lot of side effects. Sort of what Gleevac did for some cancers-dramatically put them in remission. The drug worked so well because they did the research first, made the compound second, I think.
You know how in Kramer's book he has people "better than normal" from being on Prozac? That's the type of drug I want-just exactly what happened to me for three years on Paxil. There's a country song that has the line, "and it's a great day to be alive..."-I want some of that in a bottle of pills or from a life-changing experience. Probably that won't happen today. :>}
Posted by bassman on July 14, 2006, at 10:50:51
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by qbsbrown on July 13, 2006, at 14:29:27
http://www.epilepsy.com/newsfeed/pr_1136903404.html
The percentages of patients who responded to treatment with Cymbalta, Lexapro or sugar pill (48.7%, 45.3% and 36.9%, respectively) were statistically no different.
-Percentage of patients achieving remission on Cymbalta, Lexapro or sugar pill (40.1%, 33.0% and 27.7%, respectively) were statistically no different in this study.
Posted by MARTY on July 14, 2006, at 11:09:42
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 13, 2006, at 12:39:29
> Hey! We've been though this before, remember?:>}
Actually it was with me that you've been tough this before :P
And I you already know I stand behind the same logic as SLS. It also reflect my own experience with it.
People at 60mg CEL should try 20mg LEX before going with an higher dosage. 1:3 Ration first, then if it doesn't quite do it, go for the 1:2 ratio.
Would you agree with this strategy ?
Have a nice day,
Marty
Posted by MARTY on July 14, 2006, at 11:23:59
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 13, 2006, at 14:22:02
> As I've said before, the remedyfind.com experience that the average Celexa user uses 40 mg and the average Lexapro user uses 20 mg (more or less), is pretty convincing to me as well.
hmm.. My guess is that some Pdoc haven't even heard about the S competing the R thing. Marketting should have done that job in the last years, but PDOCs aren't neurologist/biochemist and surely classified the thing as a bullshiting marketting thing in the first couple seconds. So the high majority of the PDOCS goes with the 1:2 ratio and that explains what you see on RemedyFind.com. :) that's my theory, and I too may be 100% wrong.
Have a nice day,
Marty
Posted by MARTY on July 14, 2006, at 11:25:47
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by qbsbrown on July 13, 2006, at 14:29:27
> AD's have a hard time beating placebos? Are you serious?
I think we should keep in mind that placebo effect alone is already a powerful effect on many individuals: even on depression.
Have a nice day.
Marty
Posted by bassman on July 14, 2006, at 11:26:33
In reply to Re: To Those Who Switched From Celexa to Lexapro.. » bassman, posted by MARTY on July 14, 2006, at 11:09:42
Absolutely, especially considering so many people on the board experience anxiety when changing to Lexapro. You take a person suffering from anxiety and depression and give him a drug that makes him more anxious. :>} Sort of like going to the doc and complaining that you are in pain and being given something that increases the pain. Anyway, yes, I've been here before with a couple folks on the ratio of Celexa to Lexapro. I posted an article today that solves the problem: neither of them is better than placebo, so who cares what the ratio is? SLS (Scott) was writing, if I understand correctly, that he sees the problem as one in experimental design of clincial trials. I like that-I'm also entertained by journal articles that come to wildly different conclusions. I guess we could have figured that out: if that wasn't the case, we'd all be taking that perfect med and this board wouldn't exist.
Posted by bassman on July 14, 2006, at 11:34:55
In reply to Re: To Those Who Switched From Celexa to Lexapro.. » qbsbrown, posted by MARTY on July 14, 2006, at 11:25:47
I think the point is whether or not a placebo effect is occurring, is it the darn control group that makes things hard to interpret-plus the inherent large error in dealing with an animal population (due to variation)-plus the experimental design problems, including depression inventories that come to different conclusions with the same data. I'm a determinist: I want 100% of the treated group to be signing up for samba lessons after 8 weeks and the control group hasn't moved 6 inches since the beginning of the study. :>}
Posted by MARTY on July 14, 2006, at 11:40:12
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 14, 2006, at 11:26:33
> I posted an article today that solves the problem: neither of them is better than placebo, so who cares what the ratio is?
I think it should be kept in mind that placebo alone has a powerful effect on many people, even for depression. BTW, I never saw someone going maniac on a sugar pill :P maybe sugar pill could be the way to go with Bipolar ;)
I think like SLS about the clinical trials protocol and mesurements technics. They try to be too much conservative. the scientific way. If a big consortium of scientists all around the world would work together to determine how many number there is beetween 0 and 10 I would be surprised that they arrive at a consensus of 7.4
Have a nice day,
Marty
Posted by MARTY on July 14, 2006, at 11:45:06
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 14, 2006, at 11:34:55
About the placebo vs AD, Id like to add something:Pdoc can't prescribe Placebo, but can prescribe AD. Result: 50% of the individual who are depressed are feeling better which wouldn't be the case if their Pdocs wouldn't be able to give them a pill because there wouldn't exist some ADs to prescribe. For me that's legitimate the marketting of ADs even if there aren't much powerfull than placebo.
Marty
Posted by bassman on July 14, 2006, at 13:15:40
In reply to Re: To Those Who Switched From Celexa to Lexapro.. » bassman, posted by MARTY on July 14, 2006, at 11:45:06
Good point. And what's medically unethical is to give a person a placebo instead of a drug that may do them no good, but probably will give them side effects and increase their chance of suicide. Strange days we live in.
Posted by MARTY on July 14, 2006, at 14:30:08
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 14, 2006, at 11:34:55
>> I'm a determinist: I want 100% of the treated group to be signing up for samba lessons after 8 weeks and the control group hasn't moved 6 inches since the beginning of the study. :>}
LOL! thanks you put a smile on my face.. :)
Marty
Posted by SLS on July 15, 2006, at 7:52:22
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by SLS on July 13, 2006, at 19:04:11
> > In most studies, I believe the placebo response is about 30%.
>
> This number keeps creeping higher and higher it seems.
Cool.
- Scott
Posted by qbsbrown on July 15, 2006, at 20:35:17
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 13, 2006, at 12:39:29
He said it's 2:1. He said that most insurances are now acknowledging that.
My PDOC says go to 30mg lexapro, from 60mg celexa, i'd best listen to her.
She knows more than me, and i have to trust her. Every time that i don't, and go on my own reasearching tangents, such as this, i get myself in a hole.
Brian
Posted by SLS on July 16, 2006, at 6:50:14
In reply to pharmacist agrees w/ u bassman, posted by qbsbrown on July 15, 2006, at 20:35:17
> He said it's 2:1. He said that most insurances are now acknowledging that.
>
> My PDOC says go to 30mg lexapro, from 60mg celexa, i'd best listen to her.
>
> She knows more than me, and i have to trust her. Every time that i don't, and go on my own reasearching tangents, such as this, i get myself in a hole.
>
> Brian
Theories aside, you really can't go wrong with going a bit higher than necessary as opposed to going bit lower than necessary as long as you tolerate the medication. You'll still get well. My doctor has been going pretty high with Lexapro. 40-60mgGood luck!
- Scott
Posted by bassman on July 16, 2006, at 8:13:08
In reply to Re: pharmacist agrees w/ u bassman » qbsbrown, posted by SLS on July 16, 2006, at 6:50:14
Not surprised with the 40-60 mg of Lexapro, or higher than noraml used doses of any SSRI. I had a doc who's reasoning was that SSRI's are so non-toxic that you can take any dose that works for you. Of course then there is the issue of side effects. I went from 20 mg of Lexapro to 30 mg and had all the side effects in the world; which was too bad, because Lexapro was such a good AD for me. At 30 mg, I found a slice of pizza much more appealing than any woman in the world. :>} Best of luck...looks like you are coming to a decision on this issue.
Posted by SLS on July 16, 2006, at 8:38:21
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by SLS on July 15, 2006, at 7:52:22
I thought I would post this link here, since it was relevant to the side discussion regarding placebo response:
http://www.dr-bob.org/babble/20060709/msgs/667448.html
- Scott
Posted by bassman on July 16, 2006, at 10:18:40
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by SLS on July 16, 2006, at 8:38:21
Really interesting abstract! I wonder what the actual numbers looked like. But it is in definite support of your thesis that there are "psychologically" depressed people and "biochemically" depressed people (pardon the wild over-simplification; the idea just being what the major source of the depression is)-or that there is percentage of each in an individual and when you start doing clinical trials and DON'T have that piece of info (which no one ever does), the results get screwy; e.g., drugs that we know work as AD's for some people doing no better than placebo. Of course, everyone is "biochemically" depressed independent of source and then there is the factor of how depressed a person is, in an absolute sense, versus what they report (another variable that clinical trails can't get their hands on). Have I got that right?
Posted by SLS on July 16, 2006, at 11:58:27
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by bassman on July 16, 2006, at 10:18:40
> Really interesting abstract! I wonder what the actual numbers looked like. But it is in definite support of your thesis that there are "psychologically" depressed people and "biochemically" depressed people (pardon the wild over-simplification; the idea just being what the major source of the depression is)-or that there is percentage of each in an individual and when you start doing clinical trials and DON'T have that piece of info (which no one ever does), the results get screwy; e.g., drugs that we know work as AD's for some people doing no better than placebo. Of course, everyone is "biochemically" depressed independent of source and then there is the factor of how depressed a person is, in an absolute sense, versus what they report (another variable that clinical trails can't get their hands on). Have I got that right?
Sounds good to me.
I wish the designers of these depression studies would at least use the DSM. However, I would prefer that they use 2 months as the criterion for the period of time symptoms should persist rather than the 2 weeks listed.
I have seen it suggested that the Montgomery-Åsberg Depression Rating Scale (MADRS) is more accurate than the Hamilton Depression Rating Scale (HAM-D) that I see used so often. Both are acceptable, though, from what I can see.
I think there is still quite a bit of room yet to improve the designs of clinical trials of antidepressants.
Depression is an elusive phenomenon to define and characterize. I don't think it is useful to conceptualize and generalize it as being either an entirely psychological or biological condition, although some people might very well be located at one or the other end of this spectrum. I understand what you are saying. Ultimately, every thought and feeling is the expression of a biological event. I like to say that the brain determines the mind as the mind sculpts the brain.
- Scott
Posted by qbsbrown on July 16, 2006, at 15:42:41
In reply to Re: To Those Who Switched From Celexa to Lexapro.., posted by SLS on July 16, 2006, at 11:58:27
That is hilarious and true (and sad), about the food over women.
I've realized that both 60mg celexa and 30mgs lexapro is too much for me. I feel like im on speed and/or crack (not that i've done either).
I don't eat until past noon, because im too anxious. And now that i just ate a huge meal, now im hungry again, 30 mins later.
And normally im not a sweets guy, but on this, i would rob a candy store.I think 20 lex will suite me better, or 40 celexa.
Thanks guys and gals.
Brian
This is the end of the thread.
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