![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 92 to 116 of 116. Go back in thread:
Posted by Shadowplayers721 on April 20, 2008, at 8:26:44
In reply to Re: OOOOOOOOOOOOooooooooo » linkadge, posted by Larry Hoover on April 19, 2008, at 16:44:39
Posted by bulldog2 on April 20, 2008, at 8:53:43
In reply to Re: Wierd Some I know In real Life Feel Better off ADs, posted by Phillipa on April 19, 2008, at 19:10:30
> Amazing how a simple question by me elicited so many debates. All I wondered was why some people get better and feel better when there docs decide to discontinue them. A number of posters no longer post as they no longer need ad's. One found their answer in progesterone cream. So I still believe in my opinion that physical causes can cause depression and once treated ad's no longer needed from real live people. And I see them interact daily and teach school, care for families etc. So for some a trigger set off a depression life situation or medical. This is my conclusion. Great debate though and so much knowledge. Phillipa
That is certainly another good option. Join an anti-aging clinic and let them balance all your hormones. Myofacial release massage therapy to get rid of all your muscle spasms and get everything aligned properly. I'm sure these are available in your area.Only buy organice food so you have no additives in your food.
Posted by linkadge on April 20, 2008, at 9:04:23
In reply to Re: OOOOOOOOOOOOooooooooo » linkadge, posted by Larry Hoover on April 19, 2008, at 16:44:39
>Well, the question of good science is one not >clearly ascribed to him, but Kirsch found that >antidepressants were more effective than >placebo, p <.001. Kirsch himself established >efficacy.
I'm sorry, I don't have time to review the data right now. I don't exactly agree with the conclusions you are reaching, but I can't say more until I review certain data myself. From what I understand this study reveals more when disected.
>Same goes for those who claim they didn't work. >Unfortunately, the plural of anecdote is not >data. That's why I rely on the science.
Statistical significance can mean different things in different contexts.
>The same dataset has been studied and analyzed >ad nauseum.
Thats why the conscensus is that antidepressants are only marginally better than placebo.
>No, I'm saying this Kirsch paper really sucks. >It is meaningless, but for its propaganda value. >NICE did a far better job of it, and before he >published.
NICE already suggests that for mild/moderate depression the benifit/risk ratio for antidepressants is poor.
>Antidepressants superior to placebo, p <.001.
From what I understand, in most trials analyzed, the difference between drug and placebo was not enough to exceed an arbitrary threshold established by NICE.
>And has always failed when put to critical >thinking tests. Only people like Kirsch, who can >ignore his own antidepressants significantly >better than placebo result, one chance in 1000
>(or less) that it is not a "real difference", >support the equivalence theory.You really think Kirsh was the first one to suggest that the difference between AD's and placebos is small. Kirsh's applicaton of a 'clinical significance' threshold is not arbitrary. Didn't he borrow it from NICE?
>Nobody ever argued that drugs work for all >depressives, but the clear evidence is that they >robustly work for some of them.And placebos work for others.
>And, as the combination of e.g. psychotherapy >and antidepressant works better than either one >aloneThat is certainly not a repeated finding. It is, however, logical. If you were in a study that gave half the patients two placebos (two supposed AD's) and the other have one placebo. Who do you think would fair better? Its all relative.
>that convincingly shows (IMHO) that there is >more to antidepressant response than simply >obtaining placebo response
Placebo + CBT also works better than placebo alone.
>....otherwise, therapy plus antidepressant would >be the same as therapy alone.
Well logically therapy plus placebo should be the same as therapy alone, but it isn't.
>Plural of anecdote not data, again.
But I am not claiming its data. When you make a case statement that is what is meant to be.
>Further experimentation is indeed the answer. >Including different drugs, also, IMHO. No point >limiting treatment opportunities based on >thought experiments.
>Assuming that serotonin levels are the issue. >You argued alternative mechanisms, earlier. ;-)>Whatever works, works.I'm not here to tell people not to take what they believe helps them.
>Dismissing them outright is dangerous, IMHO. >Look at what happened to child suicide rates as >a result of the warnings. Better management is >the answer, not drug avoidance.
Thats a separate issue. Don't get me started. Its called relative deprivation. SSRI's have no proven antisuicide effect. Take a look at say, overall US data on child suicide rates from 1950-2003 what do you see?
Linkadge
Posted by SLS on April 20, 2008, at 12:33:56
In reply to Re: OOOOOOOOOOOOooooooooo, posted by linkadge on April 20, 2008, at 9:04:23
I'm sure people have noticed that I'm having a bit of fun not seriously debating the issues surrounding the effectiveness of standard antidepressants. I don't really care to research psychiatric stuff anymore. I have no reason to at this juncture.
Mission accomplished. I did a hell of a good job.
It is not terribly important to me what anyone else believes, so long as it doesn't impact on my supply of effective mediation.
Besides, I have already argued these same issues before and have made my points eloquently. It was easy. The truth speaks for itself. The same people seem never to remember the results of previous debates. My previous posts can, hopefully, be found in the archives. It is easy to argue against the fallacy that drugs don't work. That's because they do. Isn't that silly? These drugs work, and some people want to argue them into disappearance. And all in the name of wanting to help me and you get well. How altruistic. <grin>
Antidepressants work. They can even bring people into complete remission. I just thought someone ought to know. It might be a matter of life and death.
Don't be a lemming following the pied-piper off a cliff. Often, people kill themselves before they reach bottom. Let the piper play his only one instrument alone.
- Scott
Posted by bulldog2 on April 20, 2008, at 13:08:52
In reply to Re: OOOOOOOOOOOOooooooooo, posted by SLS on April 20, 2008, at 12:33:56
feeling better off of meds is not the same as complete remission which is the goal of any treatment protocol. Many feel somewhat better for a while only to relapse later. There are probably millions of untreated people who drag themselves through each day feeling no joy or happiness. What does one do when all alternatives are exhausted? So you've tried diet and exercise, fish oil, sam-e, sjw, cbt etc and you still feel joyless. If you're lucky you may respond to one of the above.But some don't for one reason or another. So what are the options? A dreadful unhappy life and just accept that's the best you can do or try meds. Some on meds could not go to school or take part in a joyful life without them. I know meds don't work for everyone but let's not dismiss them as one of the options to explore.Also depressed people who are not in remission are more likely to self medicate with alcohol and or drugs.This is a complicated issue and can't be decided by individual stories.
Posted by SLS on April 20, 2008, at 13:52:56
In reply to Re: OOOOOOOOOOOOooooooooo, posted by bulldog2 on April 20, 2008, at 13:08:52
> feeling better off of meds is not the same as complete remission which is the goal of any treatment protocol. Many feel somewhat better for a while only to relapse later. There are probably millions of untreated people who drag themselves through each day feeling no joy or happiness. What does one do when all alternatives are exhausted? So you've tried diet and exercise, fish oil, sam-e, sjw, cbt etc and you still feel joyless. If you're lucky you may respond to one of the above.But some don't for one reason or another. So what are the options? A dreadful unhappy life and just accept that's the best you can do or try meds. Some on meds could not go to school or take part in a joyful life without them. I know meds don't work for everyone but let's not dismiss them as one of the options to explore.Also depressed people who are not in remission are more likely to self medicate with alcohol and or drugs.This is a complicated issue and can't be decided by individual stories.
Agreed.For so many of my 25 years of failed treatment, I would try to keep 1-3 alternatives in waiting beyond my treatment at the time. That helped me push on. In this way, I always had a legitimate reason to have hope. Sighted hope. There were many time when I figured that I would have to carry on until some unknown new treatment came around. I had blind hope at these times. Where else could I possibly derive the drive to persist? I don't know. I really can't guarantee anything to anyone based upon my successful treatment, except that I made it my business to live long enough to see this day. 25 years. Hey, I might relapse by the time I get done typing this sentence. I have no guarantees for myself.
Let us not forget though, that where non-bipolar depression of the type you you describe, there are often depressive thought styles and situational sadnesses to be dealt with. The thing that always frustrates me is that we use one word, "depression" to describe both biological and psychological phenomena. It is important to understand that where non-bipolar depression is concerned, there is a spectrum of contribution. Some are all biological. Some are all psychological. But most of these depressions probably persist because of the interaction of both.
I don't know what to say.
I think most people here know that I pray that we all get well; even the trolls. In my 25 years of treatment, I have learned that more people can get well than fail to get well with the treatments that are currently available. This will be more true with each new treatment that becomes available.
There is so much to be done. In the meantime, make it your business to stay as positive and constructive as possible. As impaired as I was, I made it my moment by moment goal to use all of what God gave me to work with.
- Scott
Posted by bulldog2 on April 20, 2008, at 14:23:24
In reply to Re: OOOOOOOOOOOOooooooooo, posted by SLS on April 20, 2008, at 13:52:56
Do you find it difficult to eat out? You never really now what they put in the food. At home I can control things. Any weight gain on Nardil?
Posted by SLS on April 20, 2008, at 14:37:53
In reply to To Scott - Diet On Nardil, posted by bulldog2 on April 20, 2008, at 14:23:24
> Do you find it difficult to eat out?
No. But I do have to ask the restaurant staff what kinds of cheese they use. The processed cheeses have never given me a problem. American and mozzerella are OK. Blue cheese is definitely contraindicated. Parmesan is out. (Not to be confused with parmigiana, which is a style of dish using mozzarella).
> Any weight gain on Nardil?
Nardil + nortriptyline are particularly difficult drugs to maintain weight on. However, now that I am responding to treatment so well, I believe my BMR has increased. I am now losing the weight that I had put on. I did have to change my eating habits. Small, more frequent meals. When I lose 40 lbs, I'll let you know. I really did not watch my caloric intake previously. Eating large dinners really did me in. There is a tendency towards carbohydrate cravings. Eat some and wait 10 minutes to see if your hunger doesn't abate. It should.
- Scott
Posted by Phillipa on April 20, 2008, at 19:31:28
In reply to Re: Wierd Some I know In real Life Feel Better off ADs, posted by bulldog2 on April 20, 2008, at 8:53:43
Bulldog I have seen a few chiropractors during nursing school although felt well shoulder pain elicited a visit to one. Wonderful the stimulating divice he used and manipulations. Problem now with that is my vertabrae forced the last chiro to say he would no longer treat me go to an ortho. Did and what a mistake. Heard there was good one here don't if accepts medicaire. Did get a heating pad again and that helps. Organic food is a waste of money in my opinion although I am a healthy eating can't justify the higher costs. And those people I spoke of are truly happy, smiling faces, outside planting flowers, hosting parties. The behavior is proof to me that for some it is quite possible. Love Phillipa
Posted by Racer on April 20, 2008, at 19:51:12
In reply to Re: OOOOOOOOOOOOooooooooo » linkadge, posted by Larry Hoover on April 19, 2008, at 16:44:39
> >... the plural of anecdote is not data.
That one line cracked me up. I laughed so hard my husband had to come out to see what caused those strange sounds -- and while he didn't laugh out loud, he smiled quite broadly.
Thank you for both a very good point made, and a very good laugh.
And, of course, for your well reasoned arguments in this thread.
Posted by Dr. Bob on April 21, 2008, at 8:55:53
In reply to Re: OOOOOOOOOOOOooooooooo, posted by SLS on April 20, 2008, at 13:52:56
> I do not want to inhabit a playground for people with personality disorders.
>
> Betula> You have an entirely naive belief in what transpires during peer review.
>
> Lar> Larry is the only one with any brains here
>
> Linkadge> The same people seem never to remember the results of previous debates.
>
> Don't be a lemming following the pied-piper off a cliff.
>
> ScottPlease don't post anything that could lead others to feel accused or put down.
But please don't take this personally, either, this doesn't mean I don't like you or think you're bad people.
I encourage anyone who has questions about this or about posting policies in general, or is interested in alternative ways of expressing themselves, to see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
http://www.dr-bob.org/babble/faq.html#enforceFollow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above posts, should of course themselves be civil.
Thanks,
Bob
Posted by 49er on April 21, 2008, at 17:26:09
In reply to They just don't work. FACT., posted by Betula on April 16, 2008, at 11:51:18
For those you not familiar with my story, I am a long term user of antidepressants who started tapering off of my meds in 2006 due to developing horrific side effects. Withdrawal hasn't been easy even doing it very slowly but I definitely feel alot better. I wanted to respond to the various issues that were raised.
Effectiveness - Lar, I am going to even attempt to refute you on Kirsh's studies because I would lose big time <smile>. However, the Star-D study revealed a 33% success rate which isn't exactly stellar. Some researchers were even mentioning a lower rate but to be fair, I will leave at at the 33% rate.
On the National Institute of Mental Health Website, it states a 50% success rate for a 50% reduction of symptoms. If you're going for complete remission, the success rate is even lower.
If those figures were alot higher, than I might think Kirsh was off target. But in light of that fact they aren't and because of the arguments presented by Linkage and Betula, I definitely agree with him.
I also think effectiveness has a different meaning for everyone.
Some might say they were effective for me. But as Betula mentioned about SSRIS, these meds made me so apathetic that I let so many things slide in my life. But what is scarier is I didn't realize what these meds were doing until I started tapering.Jealousy - I am not jealous at all of people whose meds work. To be honest, I am thankful everyday that I saw the light on what these meds were doing to me before it was too late. I suffered a mild to moderate hearing loss from Remeron, tinnitus, memory loss, executive function problems, and worsening in general of LD symptoms.
I have read on other boards that people would still chose meds for a good quality of life even if they knew there were be horrific side effects down the road. Well, in the 12 years, I was on meds, I really only had 1.5 great years. So I don't feel that is a reasonable trade-off.
Relapses - I hate to sound like broken record but in my opinion, which is backed by the registered nurse who runs the Paxil Progress Boards, most withdrawal symptoms are commonly confused as a relapse. Doctors unintentionally advocate a way too fast tapering system.
Whether I am a bad influence and discouraging people - To quote Bob, Don't necessarily believe everything you hear. Your mileage may vary. The only posts I take responsibility for are my own.
Obviously, everyone on this board has to make up their own mind what works for them. But please don't accuse me of being a troll because I chose a different path. We all want the same thing even if we go about it differently.
49er
Posted by Phillipa on April 21, 2008, at 19:09:20
In reply to Re: They just don't work. FACT., posted by 49er on April 21, 2008, at 17:26:09
Exactly the same thing that happened to my next door neighbor. She weaned off the ad's and now needs less of the high dose xanax she'd been on for years. Her energy level is incredible. And she's a teacher. Love Phillipa ps the weaning was from the same pdoc I saw who had me doing the same thing. She did it. I quit too early.
Posted by Larry Hoover on April 21, 2008, at 19:11:50
In reply to Re: They just don't work. FACT., posted by 49er on April 21, 2008, at 17:26:09
You know what? My intent was not to convince anyone to believe in drugs. It was to clear up the erroneous statements being made in the guise of being scientific findings. The truth is in the data.
It seems to me that people believe what they want to believe, notwithstanding the truth.
> Effectiveness - Lar, I am going to even attempt to refute you on Kirsh's studies because I would lose big time <smile>. However, the Star-D study revealed a 33% success rate which isn't exactly stellar. Some researchers were even mentioning a lower rate but to be fair, I will leave at at the 33% rate.
Just for the record, the main outcome measure of STAR*D: "The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%."
I think you will find the remission rate was 67%, not 33%.
> On the National Institute of Mental Health Website, it states a 50% success rate for a 50% reduction of symptoms. If you're going for complete remission, the success rate is even lower.
And what is the practical alternative? There is no placebo treatment protocol available to the general public. It is an artefact of the double-blind drug trial process.
> If those figures were alot higher, than I might think Kirsh was off target.
My argument is not with respect to the magnitude of the response to drugs, it is that is superior to placebo.
> But in light of that fact they aren't and because of the arguments presented by Linkage and Betula, I definitely agree with him.
What specifically do you agree with?
> I also think effectiveness has a different meaning for everyone.
And it's hard to understand another's success, if you have not tasted of it yourself. I do understand.
> Some might say they were effective for me. But as Betula mentioned about SSRIS, these meds made me so apathetic that I let so many things slide in my life. But what is scarier is I didn't realize what these meds were doing until I started tapering.
I don't stay on them, for just those reasons.
> Jealousy - I am not jealous at all of people whose meds work. To be honest, I am thankful everyday that I saw the light on what these meds were doing to me before it was too late. I suffered a mild to moderate hearing loss from Remeron, tinnitus, memory loss, executive function problems, and worsening in general of LD symptoms.
I want to raise another concern of mine, one that is seldom appreciated. Antidepressants have never been shown to be complete treatments for the symptoms of depression. Functional MRI and SPECT scans of brain function both show that regions of dysfunction remain, even if the subject is in full remission of depressive symptoms. Antidepressants drive normalization of some functions, but the underlying disease process continues in other respects. Appart from tinnitus (which can come from NSAIDS, as an example), the symptoms you describe can be ascribed to depression. I'm not saying that they are depression, and not drug-related. I'm suggesting that there is no way to discriminate between the options.
> I have read on other boards that people would still chose meds for a good quality of life even if they knew there were be horrific side effects down the road. Well, in the 12 years, I was on meds, I really only had 1.5 great years. So I don't feel that is a reasonable trade-off.
I wish you'd had greater success.
> Relapses - I hate to sound like broken record but in my opinion, which is backed by the registered nurse who runs the Paxil Progress Boards, most withdrawal symptoms are commonly confused as a relapse. Doctors unintentionally advocate a way too fast tapering system.That's why we're here, to offer better advice. ;-)
> Whether I am a bad influence and discouraging people - To quote Bob, Don't necessarily believe everything you hear. Your mileage may vary. The only posts I take responsibility for are my own.
>
> Obviously, everyone on this board has to make up their own mind what works for them. But please don't accuse me of being a troll because I chose a different path. We all want the same thing even if we go about it differently.
>
> 49erI'm glad you joined the discussion.
Lar
Posted by Larry Hoover on April 21, 2008, at 19:19:54
In reply to I think you should know... » Larry Hoover, posted by Racer on April 20, 2008, at 19:51:12
> > >... the plural of anecdote is not data.
>
> That one line cracked me up. I laughed so hard my husband had to come out to see what caused those strange sounds -- and while he didn't laugh out loud, he smiled quite broadly.
>
> Thank you for both a very good point made, and a very good laugh.You're welcome. I regret, I am not the originator. I can't remember were I first saw it, but it stuck in my brain.
> And, of course, for your well reasoned arguments in this thread.
Thank you.
Lar
Posted by bulldog2 on April 21, 2008, at 19:57:05
In reply to Re: I think you should know... » Racer, posted by Larry Hoover on April 21, 2008, at 19:19:54
Another thought on the subject..Maybe the fact that one felt so much better when off of them (ADS)shows they did work to some degree. One felt depressed enough to go on a med for a period of time..The depression improves but one is still left with annoying side effects. You stop the ad and you now have no side effects so you feel even better..
Now the question is now that you have stopped your ad do you feel better than before even starting the med? AD's don't have to be used permanently by everyone. Some are useful for short term situations. Maybe they shock the brain out of depression the way that ect might do.
Posted by Phillipa on April 21, 2008, at 20:05:56
In reply to Re: I think you should know..., posted by bulldog2 on April 21, 2008, at 19:57:05
Bulldog that is a good thought I like it. My example is a person who experienced corneal problems and her eyes crossed and she had surgery which corrected the problem but it flung her into depression at the time. She just continued on the meds. Now it's a thing of the past and she's physically fine. Like a cancer patient that is in remission maybe? Love Phillipa
Posted by Phillipa on April 21, 2008, at 20:45:43
In reply to Re: They just don't work. FACT., posted by 49er on April 21, 2008, at 17:26:09
49er could you post the link to the paxil support group please as have samples would like to check it out thanks Phillipa
Posted by undopaminergic on April 22, 2008, at 6:41:19
In reply to Question For Scott, posted by bulldog2 on April 19, 2008, at 15:02:40
>
> Currently doing deplin + Sam-e and getting a decent response thought not in remission.
>Have you tried adding pyridoxine, NADH, and other important vitamins and cofactors?
Why Sam-e, by the way? SAMe would be more appropriate, as it's an acronym for S-adenosylmethionine, which refers to methionine with an adenosyl-group attached at the sulphur (S) atom.
Posted by bulldog2 on April 22, 2008, at 6:55:18
In reply to Re: Question For Scott, posted by undopaminergic on April 22, 2008, at 6:41:19
> >
> > Currently doing deplin + Sam-e and getting a decent response thought not in remission.
> >
>
> Have you tried adding pyridoxine, NADH, and other important vitamins and cofactors?
>
> Why Sam-e, by the way? SAMe would be more appropriate, as it's an acronym for S-adenosylmethionine, which refers to methionine with an adenosyl-group attached at the sulphur (S) atom.Might be dropping both for a while..Deplin becomes SAMe so it is overkill to run both. Also noticed just the deplin alone was causing agitation and insomnia..Running Memantine with the deplin was muddying the waters. Will clean out and restart memantine.
Posted by undopaminergic on April 22, 2008, at 10:04:01
In reply to Re: Question For Scott » bulldog2, posted by SLS on April 19, 2008, at 15:13:16
>
> > Also at lower doses is there less chance of a hypertensive crisis if I eat the wrong foods.
>
> In reality, it depends on the percentage of MAO being inhibited in the gut. I don't happen to know what the threshold is for reducing the tyramine reaction.
>Probably the worst thing to do with regard to minimising the inhibition of gut and liver MAO is to take a single large oral dose of a MAOI, as that would lead to the highest concentrations of the inhibitor precisely in the gut and liver, before the drug is absorbed into the blood stream and greatly diluted.
Since the type A isoform of MAO predominates in the gut, MAO-B preferring inhibitors are less effective at increasing sensitivity to dietary tyramine. However, the subtype selectivity of MAOIs is dose-dependent.
Transdermal and sublingual absorption can be used to reduce exposure of gut/liver MAO to the inhibitor, while maintaining efficacy and possibly reducing the effective dose - especially in the case of highly metabolised MAOIs such as selegiline. Divided oral doses should theoretically reduce gut drug concentration in comparison with a single oral dose.
Co-administration of noradrenaline reuptake inhibitors (NRIs) reduces the sensitivity to tyramine that has been absorbed into the blood stream. In the selection of a NRI, it's important to avoid those also potently inhibiting serotonin reuptake. There is a shortage of information available on this strategy, due to long-standing fears that this combination might precipitate serious hypertensive reactions.
There is some evidence that the slow-acting rasagiline-derived MAOI (and acetylcholinesterase inhibitor) ladostigil can be taken orally without significantly affecting gut MAO while achieving high degrees of brain MAO-A and -B inhibition. Of course, this compound is still only available as the raw active ingredient.
Finally, it should be noted that there are differences in individual vulnerabilites. In studies using the 12 mg/24 h selegiline patch, 3 people (of 11) had significant (>30 mmHg) hypertensive responses to 25 mg doses of oral tyramine, whereas some required well over 90 mg. Co-administration of food increased the effective dose of tyramine by more than 100 mg. According to the same source (EMSAM prescribing info), a high-tyramine meal contains up to 40 mg.
Posted by llurpsienoodle on April 22, 2008, at 14:30:01
In reply to Re: debate » Betula, posted by Larry Hoover on April 19, 2008, at 13:33:57
"Among other things, these applications have revealed that the misuse of ordinal scaled data can produce erroneous data and drive inaccurate conclusions. Consequently, concerns must be raised over the accuracy of the results of the meta-regression performed by Kirsch et al, given they have undertaken sophisticated mathematical operations on data which do not support such activities. Moreover, it is worth noting that even the calculation of a mean, a standard deviation, and a change score are invalid on ordinal data, given that these all assume equal interval scaling."
no no no! tell me it ain't so-- the authors conducted parametric statistical tests on ordinal statistics? (can you hear me retching?)Once upon a time I was a "peer" and reviewed some truly outrageous papers, a couple of iffy ones, and one good one. There was also the paper that my advisor said "must come from lab X... very esteemed lab...I'm sure it's great..." leaving the peon llurpsie little option but to overlook significant editorial issues and infer meaning and conclusions where none were written. barf.
Maybe I have the energy to read this entire thread, now that I've interrupted it.
ll
Posted by Jeroen on April 22, 2008, at 18:26:00
In reply to They just don't work. FACT., posted by Betula on April 16, 2008, at 11:51:18
hello, i think most psychiatrists do this
they give you a SSRI, if you feel worse or say its not working after 2 weeks, then you can start thinking you have Bipolar Disorder, psychosis, Schizophrenia
fact
Posted by Larry Hoover on April 22, 2008, at 20:32:56
In reply to Re: debate » Larry Hoover, posted by llurpsienoodle on April 22, 2008, at 14:30:01
> "Among other things, these applications have revealed that the misuse of ordinal scaled data can produce erroneous data and drive inaccurate conclusions. Consequently, concerns must be raised over the accuracy of the results of the meta-regression performed by Kirsch et al, given they have undertaken sophisticated mathematical operations on data which do not support such activities. Moreover, it is worth noting that even the calculation of a mean, a standard deviation, and a change score are invalid on ordinal data, given that these all assume equal interval scaling."
>
>
> no no no! tell me it ain't so-- the authors conducted parametric statistical tests on ordinal statistics? (can you hear me retching?)Your timing is superb. I have been mulling this issue over for some weeks now, ever since I first looked at the subject paper. It just had never occurred to me to question the fact that it is standard practise to treat Hamilton or Beck scores as interval data. It is routine to read about mean improvement, standard deviations, confidence intervals......rather than median scores or quintile ranks.
But yes, Kirsch et al did multiple regressions on ordinal data.
I've been thinking that perhaps the most valid of the invalid statistics might be the number reaching a threshold, usually a 50% reduction in scores, which would be a test-retest measure unique to each subject. This threshold would serve to create a binary outcome measure, which percentage or count might then be contrasted in the experimental groups?
> Once upon a time I was a "peer" and reviewed some truly outrageous papers, a couple of iffy ones, and one good one. There was also the paper that my advisor said "must come from lab X... very esteemed lab...I'm sure it's great..." leaving the peon llurpsie little option but to overlook significant editorial issues and infer meaning and conclusions where none were written. barf.
I did literature reviews for a few years.....sifting through mounds of garbage to find the gems. I hear you, loud and clear. Although my analyses were post peer-review, I often wondered how some works had made it to print. Well over half were simply worthless.
> Maybe I have the energy to read this entire thread, now that I've interrupted it.
>
> llI would welcome your commentary. And you're most certainly not interrupting.
Lar
Posted by Larry Hoover on April 22, 2008, at 21:34:34
In reply to Re: OOOOOOOOOOOOooooooooo, posted by linkadge on April 20, 2008, at 9:04:23
> >Well, the question of good science is one not >clearly ascribed to him, but Kirsch found that >antidepressants were more effective than >placebo, p <.001. Kirsch himself established >efficacy.
>
> I'm sorry, I don't have time to review the data right now. I don't exactly agree with the conclusions you are reaching, but I can't say more until I review certain data myself. From what I understand this study reveals more when disected.I'm arguing that it reveals much less when dissected. I await your further input.
> >Same goes for those who claim they didn't work. >Unfortunately, the plural of anecdote is not >data. That's why I rely on the science.
>
> Statistical significance can mean different things in different contexts.Statistical significance has no meaning in and of itself, other than the likelihood of Type 1 error is less than some arbitrary level. Any other meaning depends entirely on context.
> >The same dataset has been studied and analyzed >ad nauseum.
>
> Thats why the conscensus is that antidepressants are only marginally better than placebo.No, that is anything but the case. That is not the concensus opinion, and basing categorical conclusions about clinical efficacy on this limited dataset is irresponsible.
The unpublished FDA data were first analyzed by Arif Khan, over a decade ago. This is what he had to say about his findings:
"The less-than-impressive results in these and other studies also calls to mind the fact that patients assigned to placebo treatment in clinical trials are not "getting nothing." The capsule they receive is pharmacologically inert but hardly inert with respect to its symbolic value and its power as a conditioned stimulus. In addition, placebo-treated patients receive all of the commonly employed treatment techniques: a thorough evaluation; an explanation for their distress; an expert healer; a plausible treatment; expectation of improvement; a healer's commitment, enthusiasm and positive regard; and an opportunity to verbalize their distress. Jerome Frank, Ph.D., in his book Persuasion and Healing: A Comparative Study of Psychotherapy made a compelling case that these parts of treatment are the active ingredients of all the psychotherapies (1993).
We also attempted to address the question about the benefits of including placebo in antidepressant clinical trials. In other words, would excluding placebo support the null hypothesis assumption in comparisons of antidepressants? As we had access to mean weekly HAM-D scores in some of the trials, we compared the magnitude of change with various antidepressants in this subsample (n=2,159). When placebo was included in a hierarchical linear regression, all of the antidepressants were shown to be statistically significantly superior to placebo. However, when placebo was excluded from such an analysis, it was found that amitriptyline was superior to nefazodone (p=0.03) and imipramine (p=0.07). Although not considered previously, it is interesting to note that antidepressants such as nefazodone and imipramine may not have seen daylight if only compared against an antidepressant such as amitriptyline, excluding placebo. In other words, placebo use may also prevent exclusion of potential antidepressants because of false negative clinical trial data.
A cautionary note is indicated about the generalization of these data to the clinical management of depressed patients. The less-than-impressive difference between drug and placebo in this and other studies of clinical trials does not speak directly to the effectiveness of antidepressants in clinical practice. Participants in antidepressant clinical trials are a highly select group and are not representative of the general population of depressed patients. They are not actively suicidal, they are almost always outpatients who are moderately rather than severely or mildly depressed, and they are free of comorbid physical or psychiatric illness. They are likely to have a higher placebo response rate than more severely ill depressed patients.
Furthermore, the primary aim of these studies is not to assess the optimal effect of antidepressants, but rather to rapidly assess efficacy of new drugs so they can be brought to the market. Therefore, dose, duration and diagnosis in clinical trials are not necessarily ideally suited to identify the optimal effects of antidepressants. Accordingly, clinical trials may identify the lower bound of the effect size compared to placebo. "
NICE published the following findings. "Strong evidence of clinical significance" is their absolute top rating. "Some evidence" is just lesser, and is used when the 95% confidence interval for relative risk includes any value greater than 0.80. Still very significant, just not quite as robust. Here we go:
There is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of patients achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 1719; n = 3143; RR = 0.73; 95% CI, 0.69 to 0.78).
In moderate depression there is some evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of patients achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 320; n = 729; RR = 0.75; 95% CI, 0.65 to 0.87).
In severe depression there is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of patients achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 5; n = 619; RR = 0.63; 95% CI, 0.54 to 0.73).
In very severe depression there is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of patients achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 6; n = 866; RR = 0.72; 95% CI, 0.65 to 0.8).
In trials lasting eight weeks or longer, there is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 8; n = 1764; RR = 0.72; 95% CI, 0.66 to 0.79).
In moderate depression in trials lasting eight weeks or longer, there is some evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 3; n = 729; RR = 0.75; 95% CI, 0.65 to 0.87).
In severe depression in trials lasting eight weeks or longer, there is strong evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of achieving a 50% reduction in depression symptoms as measured by the HRSD (N = 3; n = 535; RR = 0.63; 95% CI, 0.53 to 0.74).
In very severe depression in trials lasting eight weeks or longer, there is some evidence suggesting that there is a clinically significant difference favouring SSRIs over placebo on increasing the likelihood of achieving a 50% reduction in depression symptoms as measured by the HRSD (N= 1; n= 299; RR= 0.72; 95% CI, 0.59 to 0.88).
> >No, I'm saying this Kirsch paper really sucks. >It is meaningless, but for its propaganda value. >NICE did a far better job of it, and before he >published.
>
> NICE already suggests that for mild/moderate depression the benifit/risk ratio for antidepressants is poor.No. No they do not.
They say that only about mild depression, but if and only if it is a first presentation. If a person has a history of moderate or severe depression, antidepressants are indicated for mild depression, and if simple interventions fail. In moderate depression, antidepressants are recommended *before* psychological interventions, and SSRIs are the recommended treatment.
4.4.3.1 Antidepressants are not recommended for the initial treatment of mild depression, because the riskbenefit ratio is poor.
4.4.3.2 The use of antidepressants should be considered for patients with mild depression that is persisting after other interventions, and those whose depression is associated with psychosocial and medical problems.
4.4.3.3 The use of antidepressants should be considered when patients with a past history of moderate or severe depression present with mild depression.
4.5.2.1 In moderate depression, antidepressant medication should be routinely offered to all patients before psychological interventions.
4.5.2.13 When an antidepressant is to be prescribed in routine care, it should be a
selective serotonin reuptake inhibitor (SSRI), because SSRIs are as effective as tricyclic antidepressants and are less likely to be discontinued because of side effects.> >Antidepressants superior to placebo, p <.001.
>
> From what I understand, in most trials analyzed, the difference between drug and placebo was not enough to exceed an arbitrary threshold established by NICE.Again, no. No that is not true. Even Kirsch said: "A visual inspection of Figure 4 suggests that studies' effects are fairly evenly distributed above and below the NICE criterion...", although that didn't stop him from publishing statistics that fly in the face of what even his eye can clearly see.
> >And has always failed when put to critical >thinking tests. Only people like Kirsch, who can >ignore his own antidepressants significantly >better than placebo result, one chance in 1000
> >(or less) that it is not a "real difference", >support the equivalence theory.
>
> You really think Kirsh was the first one to suggest that the difference between AD's and placebos is small.That's not at all what I said. It takes a certain sort of closed mind to conclude something that your own statistics have shown to be otherwise.
> Kirsh's applicaton of a 'clinical significance' threshold is not arbitrary. Didn't he borrow it from NICE?
It is inappropriate to apply it in post hoc analysis, link. The studies were not conducted with any relevance to such a test, and it is inappropriate to apply it retroactively. Moreover, he purposely limits his analysis to a very small sample of all available data, includes data for a drug no longer even on the market, and generalizes to "antidepressants" when nearly 50% of the data are from paroxetine trials. And just because I can speak to it, having read the complete clinical trial data for more than one of the paroxetine trials, I can attest that the early trials (all included in Kirsch's analysis) were of very poor quality.
When new questions are posed, new research needs to be done. Looking at existing datasets can guide hypothesis construction, and perhaps influence trial methodology, but new research needs to be conducted. The subject trials in Kirsch's analysis were never meant to demonstrate clinical efficacy. They were a regulatory hurdle for licensure, and you can make out of that whatever you wish. Efficacy trials are very different......but you didn't like STAR*D because it was different.....
> >Nobody ever argued that drugs work for all >depressives, but the clear evidence is that they >robustly work for some of them.
>
> And placebos work for others.Placebo treatment is not a standard clinical practise. It is an artefact of a methodology. It has no external validity.
> >And, as the combination of e.g. psychotherapy >and antidepressant works better than either one >alone
>
> That is certainly not a repeated finding. It is, however, logical. If you were in a study that gave half the patients two placebos (two supposed AD's) and the other have one placebo. Who do you think would fair better? Its all relative.I've never heard of anyone testing your hypothesis. I was trying to incorporate something you said in earlier debates, that you thought the drug effect was an active placebo effect.
> >that convincingly shows (IMHO) that there is >more to antidepressant response than simply >obtaining placebo response
>
> Placebo + CBT also works better than placebo alone.> >....otherwise, therapy plus antidepressant would >be the same as therapy alone.
>
> Well logically therapy plus placebo should be the same as therapy alone, but it isn't.Therapy plus antidepressant is the most effective treatment for depression, is it not?
> >Plural of anecdote not data, again.
>
> But I am not claiming its data. When you make a case statement that is what is meant to be.It is uncontrolled data. It is not meaningless, but it is not the basis for any conclusions. It certainly can help shape hypotheses and future experimentation.
> >Dismissing them outright is dangerous, IMHO. >Look at what happened to child suicide rates as >a result of the warnings. Better management is >the answer, not drug avoidance.
>
> Thats a separate issue. Don't get me started.I was referring to a recent Canadian paper, which showed that adolescent suicide rates increase from 40/100,000 to 150/100,000 after the antidepressant warnings came out in 2004.
> Its called relative deprivation. SSRI's have no proven antisuicide effect.
I wasn't referring to SSRIs. Medical interventions declined, and antidepressant prescriptions declined.
> Take a look at say, overall US data on child suicide rates from 1950-2003 what do you see?
I can't find my normal data source, but this one, covering 1970 onwards, shows a steady decline from the early 90's onwards. http://www.medscape.com/viewarticle/545555_Tables#T1
One American study of adolescent antidepressant use did a county by county comparison between ADs and suicide rates, and the correlation was so robust that they developed a linear regression equation from it......for each X prescriptions, one suicide was (probably) prevented. Of course, the AD prescription rate could be a proxy for interaction with supportive medical care, but the correlation was of net benefit.
Lar
This is the end of the thread.
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