Yes, Jaclyn, the PLACEBO EFFECT (vs. Jaclyn Glenn)

now let's get back to why I am the worst
the absolute worst worse than Oni Theon proven to have no positive effect aside from what's called the enhanced placebo which he thinks is just nothing more than a placebo so anybody out there who's struggling with anxiety or depression if you are on a drug for that an SSRI more specifically in this case of what he's talking about I just hope you know that this is purely placebo [Music] early in February actually in 2008 an analysis of antidepressant medications that I did with some colleagues was published in the medical journal PLoS Medicine I woke up that morning to find that our study had become the lead front-page news and virtually all of the UK daily newspapers two years later was still making news of the four-page cover story in Newsweek and two years after that this came on television the medical community is at war battling over the scientific research and writings of a psychologist named Irving Kirsch so how did this all come about and to tell you that story I have to go back to 1998 so we combed the literature now is not enough to look at the placebo effect because you know if you if you have a cold and I give you a placebo and I measure how you're doing a week later you'll have gotten better right it's not a placebo effect that's just the passage of time Natural History so just as to measure the drug effect you need to have a placebo control to measure the placebo effect you have to have a control for natural history so what would happen if you didn't get the placebo and so we scoured the literature and we were looking for for trials clinical studies in which depressed patients had been randomized to either get a placebo or get no treatment at all being placed let's say on a waiting list and getting treatment later now as it turns out the only place we could find data on the patience yet being given placebo was in drug trials so that meant that we had the drug trial data when you have data you analyze it and what we're looking here is change creat a post in the drug condition and you get a standardized mean difference different outcome scales about 1.5 that's a big healthy effect and change improvement in medical literature and the nice big placebo response and very little improvement much less improvement in the no treatment condition so that means we do have a real placebo effect it turns out about 25 percent of the response to the active medication you get anyway even without doing anything you get another 50 percent of it by giving an inner pill a placebo that's the placebo effect in the treatment of depression fine great that's what we were interested in but now there's a surprise that leaves only 25% of the response as a true drug effect and that seemed to both gyein and and me to be too small for a treatment that had been heralded as constituting a revolution in the treatment of depression right now I can't like I usually do I tried talking to my doctor tonigh percent of psychiatrist and I got prescribed antidepressants and I've been taking down since two weeks it has a lot of side effects easier because one of the side effects is to decrease anxiety and but you still get anxiety as a side effect sometimes and another other side effects are headaches insomnia nausea and all appetite and for some reason I'm experiencing all the side-effects mr. Blunt has virtually no signs of his original illness now the signs that the movements of his mouth are completely side effects of the drugs that he was on for 20 years mr. Brown is quite rational he understands what's going on and if you're patient he can carry on a very rational conversation with you the movements that he makes with his mouth and with his tongue he can't stop their involuntary movements he can slow them down by concentrating on them but as soon as he stops concentrating on them then they come back and are more mr. blown also has some movements of his diaphragm when the diaphragm contracted then it causes him to make sounds out of his mouth but that's all part of the same condition if it was not for the side effects of the drugs mr. blunt would in all probability be able to leave the hospital [Music] FTC period until next time ask yourself a teaspoon here to sell more about diversified asset are you too skinny see sorry oppa - a saint in Sedna are the England miss feast of Italians what unknown tagowit are you too skinny see after email at all - be happening for neuroleptic entirety Tico and Atacama supported study writing I received some essential for me Teresa Hyneman even tell me cos no lipstick apprehending thre Oh too skinny she was held in the present on ax men take cigar Mecca salinity forces upon your lips iike sati in kanji are known for Sarah Merrell no lipstick Avastin illegal or declare norm so she ate steam SEC and a salon ruefully muscular prevails a man Tigers a big file mainly associate summary oh what a diagnosis it are known as a level as I said is an incident just tuned in some authority pizza salon crafty mostly spaceman some curvy Irma's Mary fool Esaias Elmo Elmo's kid means - hoo-ha hoo-ha f30 here can see four fairly scale Vietnam City will be clearly demarcate same percentage yet say Sasuke did a Mata ki simply need faded I didn't know where to go first to talk about my symptoms actually thought that nothing like was wrong I have been put on medication I went to a psychiatrist at the hospital and I told them my symptoms and and I got I know they got medication prescribed I was told that the side effects would go away I was told that the side effects would go away within a couple of weeks so I'm waiting for them to be over so in the early part of the 20th century generally it was felt that there were no there was no way of really targeting the biological origins of mental disorders and the treatment for people who were considered to be mad crazy depressed whatever was very nonspecific akin consisted of helping them to be in a creating a structured environment for them where there were activities they could do where there was work they could get involved in giving them fresh air and exercise and and if they were very disturbed using sedative type drugs but those drugs were not seen as doing anything that was related to the origins of their problem they were seen as as sedatives as chemical straight jackets or restraints if you like so that was the situation in the early 20th century and then in the 1930s and 40s various physical treatment procedures start to be introduced into psychiatry like insulin coma therapy for example and then later ECT electroconvulsive therapy now these treatments are start to be spoken of and represented as if they are somehow targeting the underlying basis of a particular mental condition so incident coma therapy for example even though no one knew for certain what it was doing people speculated that it was working by targeting the underlying basis of schizophrenia so so it was significant for that for that reason that psychiatrists even though it's not the case psychiatrists started to believe when incident coma therapy came in that they had specific treatment that targeted the underlying biological mechanism that produced schizophrenia or the symptoms of schizophrenia and the same sort of thing happens with ECT electroconvulsive therapy is introduced again for the treatment of schizophrenia but it becomes more associated in the literature anyway with the treatment of severe depression or melancholia or sometimes manic depression and again even though people have no real idea how it might be working in depression there's this idea that somehow it's acting on the underlying biological mechanisms that produce depression so by the 1950s psychiatry has gone from a state where it really didn't believe it was possible have any treatments that were thought to be specifically targeting the biological processes underlying mental disorders to a situation where it is believed commonly believed that there are two treatments that asked that specifically target two of the main psychiatric disorders incident coma therapy for schizophrenia and ect for depression or manic depression not surprisingly turned out to be very controversial and one of the most serious criticisms was that our analysis was flawed that derived from a minuscule group of unrepresentative inconsistently and erroneously selected articles what are we going to do well what we did was try to replicate our own meta analysis and we did that by where we gonna find another dataset that doesn't overlap ours and see if we can get similar results or not we went to the FDA and we use the Freedom of Information Act and we've got from them all of the data that the drug companies had sent to them in the process of getting approval for what at that time were the six widely prescribed antidepressant medication well if you look at the published trials you'll find that three out of four of them show a significant benefit of drug versus placebo if you look at the unpublished trials that shrinks 12% now we had the published trials the unpublished trials we put them all together we did the same kind of analysis that we did before and we get this nice healthy response on average to get being given the antidepressant drug and of an even bigger response I'm Lucy Bowe now it's the placebo response not the SIBO effect but we know that that counts for relatively little the-the-the spontaneous remission the natural history the placebo response is now accounted for eighty-two percent of the response to the active drug and the difference between drug and approval is less than two points on the Hamilton scale now the Hamilton scale can you can have scores ranging from zero to fifty three points you can get a six point difference just by changes in sleep patterns with no changes in any other symptom of depression that's a small difference and you don't have to take my word for it because there's an organization in England called the National Institute of Health and Clinical Excellence the acronym is nice and they're very nice organization what they do is to set treatment guidelines for the National Health Service and in revising their treatment guidelines they have established a criteria for clinical significance for saying that a drug is not only statistically but clinically better than a placebo and that's a three point difference on the Hamilton depression scale or an effect size of 0.5 and as you see that comes nowhere close when you look at it historically you realize that that idea first came about in context of treatment or the treatment ie insulin coma therapy that we now know was completely useless not only useless but highly dangerous but but certainly no one would now defend the idea that incident coma therapy was specifically treating schizophrenia specifically targeting the biological cause of schizophrenia this was a really good day and they felt really stable and sometimes you like really get happy like like this yeah I will take it easy and not let these side-effects affect me too much well it's getting better yay I must have seemed really weird at the start of the video but like it was really difficult to like turn on the camera camera but I'm still glad I did it Wow good good I probably feel like [ __ ] again like in a couple of hours but thank you it's a good band-aid it's wishful thinking basically it's wishful thinking that I think is probably quite deep-seated and people who have a medical training because because that's what medicine aims for it aims to find the ultimate causes of things and um that the mechanisms which produce symptoms and it aims to be able to target those mechanisms in some way well we published this second meta-analysis in 2002 and the critics complained that a patient's weren't depressed enough you see they said sure if you give antidepressants to mildly depressed patients or moderately depressed patients what you're going to see is probably a placebo effect there won't be much difference between the drug and effect and see both effect but you know we see severely depressed patients and in severely depressed patients that's where you'll see that the drug really does make a difference well ok that's a plausible argument what are we going to do now well let's go back to our data and let's see how severely depressed on average the patients were at baseline before being given drug or placebo as it turned out there was only one study on patients with moderate levels of depression none and mild depression one study in the early study of prozac early to clinical trial prozac showed absolutely no difference between drug and placebo there weren't any studies of patients with severe depression all of the rest of the studies were on patients with very severe depression according to the categorization used by both the American Psychiatric Association and by nice we did find within very severe depression there was a relationship between drug placebo difference its effect size and severity of depression and at the very extreme very extreme levels of depression there was a small group of studies showing patients with scores 28 or above on the Hamilton Depression Inventory show a benefit of antidepressants that in fact passes the criterion for clinical significance we had 7% who were moderately depressed 78% who were very severely depressed and only 15% who were very severely depressed but at the extreme end abut going beyond 28% they benefited in this data set that meant that about eighty-five percent did not show a clinically meaningful benefit as a function of taking the active drug doesn't that looks familiar and what does that represent in terms of distribution of patients well now we're getting a clinically significant benefit and about ten percent of the patients when you include some mildly and some severely depressed patients meaning that 90% of the patients were not showing you benefited clinically meaningful benefit and then there was the critics last resort which is a true believer high argument David Nutt in the UK said antidepressants work everybody knows they work and another critic wrote clinical practice plus millions of content patients can't be that wrong well the history of medicine is replete with treatments that have worked for millions and that's why we don't depend on anecdotal evidence for making treatment decisions we do clinical trials and we look at the data and if you look at the data everybody gets the same result here it's going to be now my study with my colleagues our studies nicest studies Turner in Canada my two harshest critics they're my harshest critics did two meta-analyses to show that we were wrong the difference between drug and placebo is small and even the FDA agrees the reason that we do randomized trials is that depression like many other conditions is not predictable so it's not the case that you know we know that you become depressed and we know you will stay like that for at least a year for example and therefore if you get better before a year's time then we can say all you know it was the antidepressant I made you better depression is not like that it's highly variable on the heart and fluctuates and therefore it is very difficult to say if someone starts feeling better whether it's due to the weather it's due to something they've done whether it's just what would have happened anyway or whether it might be due to some sort of new treatment that they've been started on and that's why we do trials and the trials show that there is a very substantial placebo response so that people feel you know a lot better when they take up to sea boat do almost as much better and there's very little difference as they do if they take an antidepressant the difference between the small difference that you see in trials between antidepressants and placebos is probably what you might call an active placebo effect it's the fact that when people take an antidepressant they're not just taking a chalk tablet they're not taking something that's inert they're taking an active drug and they will notice some more or less subtle changes from taking that drug now most people again going into antidepressant trials think once the antidepressants the people who really don't think hazard presence are going to work for them other people who don't go into those trials in the first place so if you've got a trial full of people who mostly want antidepressants mostly think they're going to be beneficial and then they take you know they get allocated to the antidepressant and they get a few side effects you've set up a situation where they're going to be hopeful you know particularly hopeful that they're going to that they're going to get better and so I think you get an enhanced placebo effect with the active medication in antidepressant trials and it doesn't matter if you look at the short-term trials or you can find yourselves to looking at the long-term trials and it doesn't matter whether you look at depression or you look at these same drugs for the treatment of anxiety disorders the difference is small barbering colleagues they did a 16-week trial comparing sertraline to placebo and to inside oriented brief inside oriented psychotherapy sixteen week trial is very long for a drug trial it's happens to be the length of trial of the star D trial patients very much like the patients who would be excluded from conventional clinical trials many of them economically disadvantaged high level of comorbidity chronically depressed and here's the part I like best non-responders at week eight people halfway through the trial they didn't respond to search Raeleen they were switched to venlafaxine good you know when drug doesn't work to try another non-responders in the placebo group or switched to a different recibo that's the part of the law here's what they got in the drug group here's what they got in the placebo group virtually no difference at all and the same level of response that you're getting in the star D trial and certainly no drug effect when we did our first meta-analysis back in nineteen ninety eight died sacristy and I when we first saw those data we assumed we must have done something wrong something is not right here everyone knows that antidepressants work maybe maybe we made the mistake of including drugs that were effective for depression as well as drugs that weren't effective for depression if we had done that maybe some antidepressants are better than others and if we're including Studies on ineffective drugs that's going to lead us to underestimates the potential of antidepressants to ameliorate depression and maybe overestimate the placebo component of it so we went back to our data and we look at looked at what drugs were the patients in these studies ah somewhere on tricyclics somewhere on assess our eyes somewhere on other antidepressants and excluded em Aiello inhibitors and things like that and we found there were some other drugs in there too there was some studies that were looking at things like barbiturates and benzodiazepine and lithium for not for unipolar depression and thyroid medications for people without a thyroid disorder unipolar depressed patients and in case after case three-quarters of the response of the drug was duplicated by placebo it didn't matter whether was a try cyclic an SSRI some other antidepressant or even something that's not conventionally considered an antidepressant here are results from meta-analyses of head-to-head comparisons between in this case SSRI and other antidepressants MDR eye sight rice eye so these are all comparator trials nope placebo controls head-to-head comparisons response rates they're all the same they're all the same and there's yet another drug that we should take into account that I don't have up here and that is TNF t how many of you have heard of TNF t very few TNF teen is a drug that is has been approved by French regulators and it is marketed in France and a number of other countries as an antidepressant the most common antidepressants these days are SSRIs selective serotonin reuptake inhibitors TNF teen is an SS ar e it's a selective serotonin reuptake inhibitors are eyes are supposed to do instead inhibiting the reuptake so that there's more serotonin available in the synapses it's supposed to enhance reuptake so that there's less serotonin available in the synapses were there any truth to the serotonin theory of depression and I don't know a responsible researcher in the area that still contends there is it's only in marketing least they'll see that talked about were there any truth to that SSRIs art should not help people recover from depression it ought to make them depressed here's what it does in head-to-head trials against both SSRIs and imipramine and tricyclics so what do you call pills the effects of which are independent of their chemical composition and they should be taken with a grain of salt just because somebody appears on the dr. Phil show claiming that she's pregnant with the reincarnation of Jesus Christ doesn't necessarily make it so just because someone appears on dr. Phil and claims that the rapper Eminem is her biological father doesn't make it necessarily so if you describe yourself with the word skeptic if you have a youtube channel and the word skeptic is in the name of your channel you're supposed to be one of the people on the side that asks careful methodological sound questions before leaping to conclusions before believing or assuming anything that reaches beyond direct empirical experience and that's a tradition that goes back to ancient Rome and ancient Greece and each and author called sexist and Perkis and there's only one one modern idea in the philosophy one thing that was added to this in the 20th century and that's the concept of falsifiability that was developed and promoted by the philosopher the scientific method known as call popper he did philosophy of science what if you want to call it okay what's the opposite of skepticism the opposite of skepticism is dogmatism skeptics should not really be embarrassed to be wrong being wrong is something that happens to human beings you might really find it convincing when you're on PewDiePie's channel watching that video letting you know that a young woman is pregnant with the next incarnation of Jesus and her biological father is mmm which would technically mean that mmm is God fascinating fascinating and shout out to PewDiePie thank you for bringing me up to date with this story thank you for poisoning a / enriching my life and mind with this completely trivial news story through doctor dr. Phil show the opposite of skepticism is dogmatism and it is dangerous dangerous in the truest sense the word when you have someone who dogmatically propounds dogmatically believes something as simple as the claim that quote antidepressants solve a chemical imbalance in the brain it wouldn't take a genius to just read the fine print that's now written on every bottle of Prozac you wouldn't take a genius to do a little bit of google searching and a little bit of fact-checking and to realize how genuinely contestable these claims are and even if you don't come to a conclusion to do that most basic thing that skepticism requires skepticism isn't about coming to conclusion skepticism isn't about always being right skepticism isn't about never being wrong being wrong is something happens to human beings and it's part of the scientific process skepticism is about admitting to yourself when you do not know I didn't know where to go first to talk about nice simple actually thought that nothing fake was wrong the people who are harmed by these drugs are reaching out for help these drugs end up hurting people who are weak and they end up hurting strong people at moments in their lives at times in their lives when they're at their weakest it's exactly when they're most devastated distracted and demoralized when they can't take the time to get on google get on you to get on Wikipedia and figure out these facts lurking behind the figures when they can't scrutinize what their doctor or psychiatrist is telling them and that's why I say again please do your small part share this video share it with someone you love share with someone you're concerned about Cher it so that we can help the whole world catch up with what dr. Irving Kirsch already knew in 1998 I mean people like to disrespect my truth but the fact is that you know my name is I don't know