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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 295 to 319 of 8406. Go back in thread:
Posted by dr dave on September 4, 2002, at 15:12:33
In reply to Re: Raines et al/see bottom » Patson, posted by pharmrep on September 3, 2002, at 0:58:11
You have mentioned the Sanchez paper which shows Lexapro raising brain serotonin more than an equivalent dose of Celexa. This seems to show r-citalopram impeding the action of s-citalopram.
But there is another side to this. Another paper by Sanchez compares the potency of Lexapro and Celexa. The results are in terms of IC50 - the concentration required to inhibit serotonin re-uptake by 50%.
2.1 nM of Lexapro inhibits re-uptake by 50%, whereas 3.9 nM of Celexa is required. So Lexapro is about twice as potent. But let's think about this. Once Celexa is absorbed, you end up with 36% s-citalopram and 64% r-citalopram in the circulation. So the concentration of s-citalopram needed to achieve 50% inhibition, when r-citalopram is also present, is 36% of 3.9nM - only 1.4nM!
So from these results, r-citalopram helps s-citalopram with serotonin re-uptake inhibition! This is pretty definitely not true, but it demonstrates how unreliable individual results can be, and if you pick out the right results you can make them say all sorts of improbable things. This is why I feel it is so important to look at all the data.
I think we should be able to examine the trials which have been done comparing Celexa and Lexapro. Currently (as far as I am aware) the comparisons from only one of three trials has been disclosed (Burke et al). The study written up by Lepola et al and Montgomery et al has had the citalopram data removed, for no apparent reason. The third trial has not been disclosed at all.
I think we should be able to have access to all the information so we can make up our own minds.
Posted by Patson on September 4, 2002, at 22:39:44
In reply to r-citalopram impedes s-citalopram?, posted by dr dave on September 4, 2002, at 15:12:33
Hey,
I just read an article on the Nobel Prize in Chemistry for the scientists that created the technology allowing scientists to "cleve" a molecule and isolate the single isomer of a racemic compound. Just thought that was kind of an interesting addition to the current discussion of isomer science.
Posted by pharmrep on September 4, 2002, at 23:33:31
In reply to Re: Lexapro effects » pharmrep, posted by WINGER on September 3, 2002, at 1:49:04
Lexapro has the cleanest cyp450 system (liver metabolization) of all AD's. Celexa was the cleanest before, only mild inhibitions in the 2d6 and 1a2...Lexapro has 0 (negligible) inhibitions in all the pathways..3a4,2d6,1a2,2c19,and 2c9
(In otherwords...it is nearly impossible to get a drug-to-drug interaction with Lexapro...which is good news for anybody on multiple meds.)
> Does this mean that lexapro will be easier on the body and the liver especially??
> None of the doctors I know want to talk about what all of these do taken together to your organs that process them... they all poo poo it and act like you're crazy for worrying about it..
> It's like we're all one big long term experiment!!
>
>
> > > > > Why don't the study results indicate any positive conclusions about fewer ASE's or daytime sleepiness?
> > > > > Appreciate your info.
> > > > > JaneB
> > > >
> > > > ** Why do you think they dont? There are studies that show reduced s/e with Lexapro...here is a post from a couple days ago that has the FDA approved package insert info.
> > > > Re: Lexapro side-effects » dr dave
> > > > If you have any questions...I'd be glad to help if I can.
> > >
> > > Pharmrep,
> > >
> > > What about antidepressant induced sexual dysfunction? I saw the results you posted. Am I missing something or has this issue not been evaluated with Lexapro? What if 40 mg Celexa causes cycling and 20 mg is used. Can/should 10 mg Lexapro be cut in half to avoid this risk? I know package inserts don't cover these intricate side effects. Just wondered if you have inside information.
> > > JaneB
> > >
> > > **good news and bad. As far as cycling...I cant help you there...as far as sex. s/e...here's the scoop...5+ years ago, when Celexa was coming out the sex. s/e was at 6%. Back then (pre Viagra era and others) people were not very willing to mention sexual disfunction (embarrassed?) Anyway, we know that 6% was low...it was more like high-teens, or low 20's (Paxil and others had same problem and are believed to be 30%+.) Since Lexapro study was done in last year, we are hoping for a more "believeable" number since todays responders are more "aware" of the sexual s/e topic, and are more willing to bring it up. Anyway, the Lexapro number is 9%...it is believed to be slightly lower than Celexa, due to its increased Serotonin selectivity (there seems to be a connection to the more selective, the less the sex. s/e.) Ultimately, any AD working with serotonin will affect sex s/e. It's just a question of how much.
> > PS...the only mg's are 10mg and 20mg (but they are scored...the idea is so you can use 15mg...but of course some people do respond differently and maybe 5mg is good for some, however it has not been tested...10mg is the "normal" starting and maintenance dose. (And this is all in the P.I...read up if you can find it.)
>
>
Posted by pharmrep on September 4, 2002, at 23:47:12
In reply to Sexual/anxiety SE question for everyone/pharmrep, posted by johnj on September 3, 2002, at 11:23:30
You need to ask your Dr about Lexapro...Forest is going to start giving the Dr's samples and studies starting 9/5...there can be sexual s/e with AD's that affect serotonin. Lexapro showed a 9% possibility of have ejaculatory delay (not always a problem). But it was not enough to discontinue treatment (only 6% dropout rate for various reasons.) As far as titrating goes...couldn't be easier...everyone starts at 10mg...most patients should see a difference in 1-2 weeks, and if necessary go to 20mg, but that should be necessary for a minority of patients...most will do fine at 10mg. As far as anxiety...Lexapro will help that, not contribute to problems. Look for the Burke, Gorman, and Lydiard studies for proof-sources.
> I have never taken an ssri and need to switch. What do you mean when you say sexual side effects? Lack of desire?, feeling?, etc. Also, would it be desirable to titrate up very slowly with lexapro to decrease the chance of initial anxiety? I have heard it can be a problem at the start and I want an AD with anxiety relieving properties. Anybody feel spacey on Celexa? Remeron made me a space cadet. Thank you
> johnj
Posted by pharmrep on September 4, 2002, at 23:52:36
In reply to Re: Reports from people taking Lexapro » dr. dave, posted by johnj on September 4, 2002, at 8:27:02
> How could they have used Lexapro if it isn't out in the US? One used it a few days at most and said it didn't work? I thought a trial of weeks was needed? Are these for real? Something sounds fishy
** I agree...I am positive that no early sample studies were done...perhaps they got it from UK? Anyway...there will be more feedback starting soon since it's in US now.
Posted by pharmrep on September 5, 2002, at 0:06:31
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by Bill L on September 3, 2002, at 9:48:28
> The way I see it, a switch from Celexa to Lexapro would be prudent. Celexa has a drug in it (the R-enantiomer) which apparently has NO antidepressant activity. In fact, it may be harmful in terms of making the active ingredient less effecive. And also it might cause side effects. Why would anyone want to take the R-enantiomer? Why put a drug in your body that is not helpfull and that might be harmfull?
>** Of course it is a guess, but Forest is anticipating Lexapro getting its prescriptions from about 1/3 of patients on Celexa and about 2/3's of patients on other AD's. Remember..Lexapro is for patients who feel their current AD is not working or the s/e are not tolerable...not just switching because its "new."
Posted by dr dave on September 5, 2002, at 2:31:05
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by Bill L on September 3, 2002, at 9:48:28
Anybody?
Any evidence? If it's going to be repeated and repeated that Lexapro has fewer side-effects than Celexa, can anyone provide the evidence to back it up?
Things seem to have gone a bit quiet with regards to this question.
Posted by Anyuser on September 5, 2002, at 9:56:45
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by dr dave on September 5, 2002, at 2:31:05
"Evidence" for you is something different than "evidence" for a potential user of Lexapro and also different, I'll bet, for most practitioners. I'm not trying to win a scientific argument. I am trying to make reasonable and, I hope, effective decisions about which medicine to take for a mood disorder. "Evidence" for me means "useful information." For the moment, the best such evidence about Lexapro is the FDA-approved prescribing information that says that the incidence of adverse effects associated with a therapeutic dose of 10mg Lexapro is the same as placebo. That's pretty good reason to believe that Lexapro is worth a try, as compared to the FDA-prescribing info for the alternative SSRIs. In a couple of months we'll have additional "evidence" in the way of the reported experience of Lexapro users and prescribers.
Posted by pharmrep on September 5, 2002, at 10:17:28
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by dr dave on September 5, 2002, at 2:31:05
> Anybody?
>
> Any evidence? If it's going to be repeated and repeated that Lexapro has fewer side-effects than Celexa, can anyone provide the evidence to back it up?
>
> Things seem to have gone a bit quiet with regards to this question.** I do agree with Anyuser's statement...the FDA has approved the statement "Lexapro 10mg/day had an overall incidence of side effects comparable to placebo" and "Lexapro 10mg/day showed no significant diference in drop-rates due to adverse events vs. placebo." (As written in the Lexapro package insert)
I have to ask you something DR. Dave...has any representative from Lundbeck seen you? I am thinking you have not gotten any input/presentation from them, posters of studies or samples....or have you?
Posted by dr. dave on September 5, 2002, at 10:34:28
In reply to Re: evidence » dr dave, posted by pharmrep on September 5, 2002, at 10:17:28
> > Anybody?
> >
> > Any evidence? If it's going to be repeated and repeated that Lexapro has fewer side-effects than Celexa, can anyone provide the evidence to back it up?
> >
> > Things seem to have gone a bit quiet with regards to this question.
>
> ** I do agree with Anyuser's statement...the FDA has approved the statement "Lexapro 10mg/day had an overall incidence of side effects comparable to placebo" and "Lexapro 10mg/day showed no significant diference in drop-rates due to adverse events vs. placebo." (As written in the Lexapro package insert)
> I have to ask you something DR. Dave...has any representative from Lundbeck seen you? I am thinking you have not gotten any input/presentation from them, posters of studies or samples....or have you?I've seen a Lundbeck rep and I have also had several lengthy conversations with Dr Joubert Gama, Medical Affairs Officer for Lundbeck UK. I've seen all the papers and posters available, to my knowledge - certainly Lundbeck say they've sent me everything that's available.
Posted by Dinah on September 5, 2002, at 10:34:59
In reply to Re: evidence » dr dave, posted by pharmrep on September 5, 2002, at 10:17:28
Posted by pharmrep on September 5, 2002, at 21:39:12
In reply to Re: evidence » dr dave, posted by pharmrep on September 5, 2002, at 10:17:28
Well I must say...today was weird. I saw 11 Dr's today. All of the highest prescription writers only. I would normally get 10 seconds for a signature up to 2 minutes max with any of them in the past, yet today I got a range from 5-20 minutes. I felt like I was at Disneyland..running around from ride to ride, but only going on the "big" ones. There's definitely many questions and interest in Lexapro out there. The Dr's are eager to read the data and learn. From the responses I saw today... I would say there was a lot of interest before launch, and even more now, and the Dr's want to see how well Lexapro really works.
Posted by psycHarvard on September 5, 2002, at 23:16:05
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by Bill L on September 3, 2002, at 9:48:28
I am a clinical instructor in Psychology with Harvard and I have had experience in depth with Lexapro since it was licenced by forest from Lundbeck in 98.... yes that is right it has been developed over a few years now and the reason that forest is now promoting Lexapro is simple and so many people here are uninformed and jumping to conclusions that I had to spell it out for them...
Lexapro is the next generation in SRI therapy.... next generation remember that it is important... first generation SSRI (Lexapro is in the SRI class) was Fluoxetine and there has been no huge improvement in SSRIs since then... a little cleaner and little more tolerable... so in that respect lost boy is correct... but now this is where some of you may feel challenged... Lexapro is the next generation of SRI therapy... what this means is basically that Lexapro is the most selective of any anti depressant... for 5HT without hitting on any of the other monos... this will decrease AE profile and reduce psycho activating events... I am trying to keep this as simple as possible... Lexapro has advantages over other anti depressant due to the fact that it only hits one mono as hundreds of studies show (Freemantle is a good one) that any more than one will just cause more AEs and a decrease in pat compliance... at any rate the SNRIs available only hit both 5HT and NE at the highest titrated dose so if you are on anything less you have fallen for a marketing ploy.... not that I do not believe that they are efficacious.
I have a lot of information that I am willing to share but I will only mention a bit at a time.
Posted by Phil on September 6, 2002, at 8:27:35
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by psycHarvard on September 5, 2002, at 23:16:05
May I ask what your involvement was in the studies?
We're uninformed about Lexapro because of a lack of subjective information.
I'd like the answer to three questions, if you will. Sexual SE, less or more than Celexa- -Weight gain, less or more than Celexa- -Emotional blunting and apathy, less or more than Celexa.
I'll be switching to Lexapro from Celexa early next week. Any info appreciated.
Posted by Dinah on September 6, 2002, at 9:03:22
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by psycHarvard on September 5, 2002, at 23:16:05
> I am trying to keep this as simple as possible...
Well, if you were speaking only to me, it would probably be best to keep it as simple as possible. But a lot of people on this site are quite comfortable with this sort of talk (moreso than my pdoc in fact) and would relish a complex explanation. Then they could translate for those of us who need a simpler explanation. :)
> I have a lot of information that I am willing to share but I will only mention a bit at a time.
>Well it's your choice of course, but again, I think people would enjoy hearing it all at once. It might take a while to digest it all, but it might also allow the information to be coalesced in a way that hearing it a bit at a time wouldn't allow. So feel free to hit us with it all at once.
> at any rate the SNRIs available only hit both 5HT and NE at the highest titrated dose so if you are on anything less you have fallen for a marketing ploy.... not that I do not believe that they are efficacious.
>
Hmm. Okay, as I admitted, I am *not* one of the people who understand neurotransmitters that well. Are you saying that a SNRI such as Effexor is doing for both 5HTP and NE what Lexapro will do for only 5HTP? Or am I totally misunderstanding? Because I have to say that Effexor was just as bad at sexual side effects for me as a straight SSRI. The fact that its effect on NE was disastrous for me is probably beside the point.At any rate, the whole discussion is probably only important from a theoretical point right now. Phil and others are going to try Lexapro. In just a few short weeks, the anecdotal evidence will start coming in. And I trust the anecdotal evidence more than all the studies in the world because in my experience it has been more accurate. I've had doctors tell me over and over again that this or that experience can't be caused my my med, when I come here and find out it's pretty common.
Posted by Dinah on September 6, 2002, at 9:04:10
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by Dinah on September 6, 2002, at 9:03:22
Posted by johnj on September 6, 2002, at 11:23:27
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by psycHarvard on September 5, 2002, at 23:16:05
I have a question for you maybe you can give me a hint upon the causes. I am at 50 mg nortrypline, 600 mg lithobid, and 15 to 22.5 or tranzene. I have depression with a high level of anxiety. The problem is if I excercise I feel like crap after a regime has been started. Sometimes the next day I will feel more depressed and have sleep disturbances. I have taken care to watch the time I work out, what I do and what I eat. I take in enough sodium so it is not a spike in lithium. I believe it is the TCA somehow. Have you ever run across this? What have atheletes used that have been sucessful to treat anxiety and depression. I am hoping a switch to lexapro will give me the power back to help myself through excercise. Also, what is the deal with increased anxiety with ssri's? I went to a Celexa board and almost 90% complained of worsening anxiety. Any thoughts? Thank you.
PS. I tried remeron and it gave me a "sponge head" and messed with short term memory.
Posted by Anyuser on September 6, 2002, at 11:48:29
In reply to Re: Fewer s/e with Lexapro - where's the evidence?, posted by psycHarvard on September 5, 2002, at 23:16:05
In my opinion, any posters that announce themselves as a physician, whether teaching, research, or clinical, should identify themselves further. Dr. Dave did this, sort of, by linking to an article in which he was quoted and identified.
Pharmrep let us know where he is coming from, so we can take into account his bias when weighing what he has to say. I suspect there is a least one other poster on this topic with commercial interests, who has not been as candid as pharmrep.
Posted by Phil on September 6, 2002, at 12:42:25
In reply to Who are you? » psycHarvard, posted by Anyuser on September 6, 2002, at 11:48:29
Posted by ZyprexaNumbTongue on September 6, 2002, at 14:37:39
In reply to Sharing info a little at a time...hmmmm..? (nm), posted by Phil on September 6, 2002, at 12:42:25
Somebody here must set the record straight and stick to the hard facts about Lexapro. Rather than using emotional claims to incite enthusiasm for this new antidepressant. Here are the hard, cold facts about Lexapro.
1) Lexapro is formally classified as an SSRI. Lexapro is not a truly new or novel antidepressant such as a CRF-Antagonist, subsance P drug, an MAOI patch or other drug.
2) Lexapro has been tweaked pharmacologically to supposedly remove some undesireable side effects like SSRI delayed ejaculation. This may...or may not be true. Only time will tell. The studies which claim this are studies done by forest labs, which should be taken with a grain of salt.
3) When reading studies about psychiatric drugs, several things must be kept in mind. First, educated people are skeptical about statistical studies. Unless the studies are done by TOTALLY objective organisations who have no conflicts of interest with the drug. In plain English, any study done abou Lexapro doesnt have a huge amount of credibility unless done by an organisation totally unconnected to Forrest Labs and is not being paid by Forrest Labs.
The U.S Census Bureau is an example of an objective organisation, with no conflicts of interest. Pharmaceutical companies however, have conflicts of interest out the wazoo and thus are unlikely to be able to remain truly objective and honest about their drugs.
Its imperative that any studies done about Lexapro, the organisation doing the study must have no conflicts of interest with Lexapro or Forest Labs. In the case of the Forest Labs/Lexapro studies, you have automatic built in conflicts of interest. Therefore, you should real these studies with EXTREME skepticism.
It should also be remembered that when the other SSRIs came out (Prozac, Paxil, Zoloft) that the studies which came along with these SSRIs also indicated low levels of sexual dysfunction such as delayed ejaculation. This was quickly proven to be untrue and sexual dysfunction has been proven to be a major reason why depressives discontinue SSRIs.
Statisics can be skewed, distorted, etc. to make a product look good or better than the competition. The odds of this happening are higher when he statistics are done by the company which makes the product in question.
4) The studies dont describe the TYPES of depressives in the Lexapro studies. All too often, antidepressant clinical trials turn away those with the severe form of depression known as the melancholia subtype (true severe depression) and actively recruit those with milder to moderate depressions (dysthmics). This is a poor way to assess the effectiveness of a new antidepressant. Id like to know how many melancholic depressives were included in Lexapro clinical trials.
My best is that most of the people who took part in Lexapro studies were dysthymics or people with moderate depression. People who by and large could still function in life without drugs, people who could still work, etc.
We need more drug clinical trials where the people recruited are those with SEVERE melancholia type major depression, not dysthymics and moderate depressives. My prediction is that many antidepressants on the market would not be approved so fast by the FDA if this were to happen.
Of course, many drug companies would love it if they could develop "cleaner" SSRIs which have no real side effects such as delayed ejacuation, weight gain, etc. Why? Because then they would be able to target the HUGE dysthymia market and sell more Lexapro. Lets face it, there is a lot of dysthymia in this country, but dysthmics can still work, function in life, etc. Drugs arent really needed to combat dysthymia. There are other ways. However the drug companies would like EVERYBODY to take these SSRI drugs, simply cause it means bigger profits. But most dysthmics wont tolerate a lot of side effects, whereas a person with severe melancholia type depression will tolerate a lot of side effects.
thus there is motivation to develop newer SSRIs which have minimal side effects...to get all the dysthymics on antidepressants. This is pathetic.
5) and finally as LostBoyinNC has pointed out, remember who "pharmrep" is. Pharmrep is a Lexapro drug salesman for Forest Labs. The more Lexapro that is sold, the bigger the profits for Forest Labs...and the better paycheck pharmrep gets. Thus he may not exactly have the depressives true welfare in mind. Like any salesman, they want to sell their wares, in this case Lexapro.
Posted by IsoM on September 6, 2002, at 15:06:50
In reply to The hard, cold facts about Lexapro, posted by ZyprexaNumbTongue on September 6, 2002, at 14:37:39
I agree with most of what you've written but do reserve judgement about some. But one thing I do disagree with is to infute the motives of someone you've never met face-to-face. It's important to not include personal opinions of others here.
I may sound naive but I prefer to believe what someone states about themself until proven otherwise. We can gather all the hard facts from different studies but we can't gather facts on what an individual's motives are that easily.
While I take these posts with a grain of salt, I believe pharmrep, while touting Lexapro, does hope that it's as good as it claims to be. Whether I think it is, doesn't matter. But I think his motives are essentially good. Just as I believe Dr. Dave's motives are too.
Making comments about someone's motives doesn't advance your views, but will only serve to make them less credible to others.
Posted by ZyprexaNumbTongue on September 6, 2002, at 15:12:38
In reply to The hard, cold facts about Lexapro, posted by ZyprexaNumbTongue on September 6, 2002, at 14:37:39
Hi Pharmrep, I would like to know about the types of depressives who took part in these Lexapro clinical trials.
1) How many of them had severe depression, the type generally referred to as the "melancholia subtype" of depression? This type of depression is also known as endogenous depression and consists of severe deteriorations in sleeping cycles especially severe insomnia, losing weight and appetite without trying, losing sex drive and losing sexual functioning, losing normal cognition such as inability to concentrate, remember, decide, think clearly, etc. Also, melancholic depressives tend to lose their sense of taste and smell. Did Lexapro restore sense of smell and taste?
2) How many of the depressives in the Lexapro trials were recruited and had milder to moderate forms of depression known as "dysthymia."
3) what were the full remission rates for Lexapro?
4) What were the full remission rates for the people who had the severe melancholic form of depression? Or did these people just get a "response" and improve some, but not get totally well?
How many of these depressives in the Lexapro trials were considered disabled and unable to work? Did Lexapro restore their disability and make them undisabled and able to work?
These are very important questions for you. I am not sure you will even know the answers to these questions, but Im asking anyway.
thanks,
Posted by Anyuser on September 6, 2002, at 15:23:46
In reply to The hard, cold facts about Lexapro, posted by ZyprexaNumbTongue on September 6, 2002, at 14:37:39
FWIW, the manufacturer has tried out Lexapro on severely depressed patients: http://www.docguide.com/news/content.nsf/news/8525697700573E1885256C280059CC1D?OpenDocument&c=Depression&count=10&id=389736e1a5d7a79d85256c270052d0a8
Posted by ZyprexaNumbTongue on September 6, 2002, at 15:46:52
In reply to severe depression » ZyprexaNumbTongue, posted by Anyuser on September 6, 2002, at 15:23:46
> FWIW, the manufacturer has tried out Lexapro on severely depressed patients: http://www.docguide.com/news/content.nsf/news/8525697700573E1885256C280059CC1D?OpenDocument&c=Depression&count=10&id=389736e1a5d7a79d85256c270052d0a8
Hmmmmm but it says the "manfacturer" of Lexapro has tried it out on severely depressed patients. What about organisations not tied to the manufacturere? What were the results?
Have there been any tests to compare the results of Lexapro in severe, melancholic type depression with the results of say high dose Effexor, bilateral/bifrontal ECT or high dose MAOIs? Im just curious.
the manufacturer is likely to say about anything about Lexapro, keep in mind.
the article didnt mention remission rates from Lexapro in severe depression. The goal in severe depression is full remission, not a 50% "response."
Did you know that to get approval as a new antidepressant by the FDA, all a drug has to prove is that it reduces HAMD scores by 50%? Thats all. A drug doesnt have to prove it causes full remission, just a response.
How much money was spent bringing Lexapro to market BTW?
Furthermore, how do you know whether Solomon's son had the real deal, melancholia subtype of depression? I scanned his book and it has lots of introspective BS stuff in it, that reminded me more of a "issues" type depression than an endogenous depression that needs ECT.
ZyprexaNumbTongue
Posted by Anyuser on September 6, 2002, at 16:10:00
In reply to Re: severe depression, posted by ZyprexaNumbTongue on September 6, 2002, at 15:46:52
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