"Medication of Sadness" with Robert deRubeis, PhD

"Medication of Sadness" with Robert deRubeis, PhD



okay thanks Martha it's great to be here I all about you very impressive group its great to have people travel here and with each with your own perspective and I'm certainly going to be looking for that particularly in that half hour in an hour or so and you know I've been very lucky to be here at Penn and and wonderful colleagues like Martha and then also I get what I think are the world's best graduate students I mean you know and one of those is here today Lorenzo and and really a good stretch of today's talk is comes out of my being having been educated over the last couple of years by Lorenzo and through Lorenzo some people I'm going to be telling you about but I'm gonna also gonna be talking about data that we've collected and how we've thought about that and some larger issues but the whole business of medication of sadness that whole idea of sadness you'll see is featured quite a bit and that the the way of looking at things in which I'll use the word sadness a lot does really come through Jerry Wakefield and Ellen Horowitz from them through Lorenzo and we'll we'll get to that all right so um you know I grew up in in my clinical psychology training sort of just as I think psychiatrists wanted to be have legitimacy with the rest of the medical profession and that explains quite a lot about what's happened in the development of of psychiatric diagnosis and treatment over the last 50 years or more in a similar kind of way I think psychologists like myself wanted to get legitimacy with psychiatrists and within the mental health field and so I very much swallowed I shouldn't say so I'm very much went along with and tried to understand the the the field as it was forming itself in the early 80s with a DSM 3 introduction in that whole business I mean this is right in the midst of my training and we were you know very serious these were disorders these were things that could be identified and and they were serious and of course they still are and we're just gonna learn more and more about these things we're gonna figure them out and we're gonna come up with specific treatments because we're gonna understand the mechanisms and so on and so on and it looked like the that was happening in psychiatry that they were figuring it out and they were coming Oh their mechanism I'm a bit less a bit more skeptical about all of that than I was 30 years ago and in fact I would say the state of if you'd asked me what the state of our knowledge then was about mechanisms and stuff such in some ways I would have answered you not just more optimistically 30 years ago but I would have said that we were pretty well along and now I don't think we were as far along as I thought we were 30 years ago anyway enough of that so just to tell you that we're talking at least at the beginning about something that's very serious and something that needs our serious attention as as a problem as opposed to something interesting to try to overcome sadness and so on this is not this this bit here is generally not about sadness it's about the the fact that we have individuals who are laid quite low by different what we can call depressive disorder it's you know the we know that you know we studied it we and others hmm oh well something's happened in the translation but at any rate the we've learned that's stressful life events or losses very often precede these episodes of depression we understand that there there certainly must be even if we've not not convinced we've identified which ones there must be genes that predispose people to be vulnerable to certain kinds of environmental inputs and so there's quite a lot of interest and I'm sure you've certainly read about these kinds of things I won't go into the the business with the serotonin transporter gene but that that and that gene and others have attracted interest so at any rate one one way to look at depression is to think about it Martha and I have talked to quite a bit about this and other colleagues as well it's a depression as a disorder or as a pathology can is interesting in that we can think about it as engaging two very different sets of functions which we know or well we know are supported in two very different parts of the brain so we can think of the problems with depression as being something that's just regulated or something that's not working quite right in the generation of emotion if you will in the the sort of triggering of basic drives we see those is having happening more in the primitive brain and then we can also think of depression as something that either we can think of it as as arising from a dysfunction of executive function or an insufficient or inadequate or inefficient use of executive function to manage life and life and emotional things in life or we can also think of it in a complimentary way as that the the neocortex can be used with new training such as say cognitive therapy to address what might be might be pathologies or disruptions in the limbic brain and of course either of these things at least in principle even either of these brain areas at least in principle could be affected nicely or well just could be affected by medications by transcranial magnetic stimulation any any of the kinds of treatments could could in principle address either of those dysfunctions if we if we think of those as two areas in which we might find dysfunction now you know this is to show you because we're gonna be getting to some stuff later on where we're not talking about depression as profound as this this is one kind of extreme this is a famous person and I'm gonna predict at least one of you in this room knows now you don't count Martha ya knows who said this I'm now the most miserable man living if what I feel were equally distributed to the whole human family there would not be one cheerful face on earth any any guesses yeah how about that how many points are we giving Martha for well wait a minute you're on the fact no no so you know points for you but yes you're correct Abraham Lincoln I ran across this on a visit to Washington a few years back and I'm not a big note-taker as some of my students know but this one I had to write down it was on some monument at the write down where it is so all right so we know that there are evidence what I'll call evidence-based somatic treatments I don't know how much you all have been talking about this stuff here I know you've talked some about medicines but I'm gonna talk about particularly the evidence in regard to depression and they really fall into a few different categories electroconvulsive therapy very effective when it's used very not often used we can talk about that later if you like antidepressant medications slides seem to have cleared up that's nice antidepressant medications introduced in the 50s starting with MAO inhibitors and then what we've seen have been thought of as advances each time and of course you'd hope they would be advances because you shouldn't be doing a retreats but the advance of course when the Mao Eyes was because there are some issues in terms of diet and some some risk for some some bad side effects there particularly in really in interaction with diet when the tricyclics came along those were seen as more better tolerated when the SSRIs came along when I talked about a lot about that many things changed and the and and by many things I mean on the plus and the minus side and we'll talk about what the effects have been and then then they came the nonspecific reuptake inhibitors okay the NSR eyes such as effexor which the the big marketing thing there was there were so much better than the SSRIs because they were like this okay because they hit both systems and of course when by both we mean serotonin norepinephrine and now of course that people do understand that dopamine systems and other systems are also affected and so on but I actually went to a talk by a guy like I admire quite a lot who came and said that ooh Barney Carroll who came to pana gave a Grand Rounds in which he made it very clear that these were supposed to be better because they were dirty drugs and so at any rate interesting historical points that we could pursue a bit if you like so it turns out that the depressant medications even though really only these are used very much in the u.s. these days the SSRIs in the NSR eyes it that's largely because those are the ones that are talked about I mean there are differences that that a well-educated physician who's using these things will be considering other than the fact that these are the ones they've heard of and that are kind of popular and tolerability so a big big change that happened with the introduction of Prozac and it's in its neighbors or its cousins is that patients were not complaining the the day or two after they started taking the meds or even a week or two after they started taking the meds now and they wouldn't weren't complaining about dry mouth and you know dizziness and so on those clear vision the kinds of things that the tricyclics brought about with some regularity and but they did they do start complaining and those of you who treat patients or see patients know they do some of them start complaining after a while as they get fatter or as they find that even though there may be feeling better in terms of their depression they don't have sex with the partner that they look that they love so there are the sexual side effects and and some other things kind of they're not the things that are noticed immediately so that's an interesting problem so but then a suicide risk potential is also very different I mean this one's controversial what I would say is that it's certainly the case that you can kill yourself by using tricyclics as the means that's very very hard to do with the modern medications so i'm that side that was a big deal was that you couldn't you know use your treatment to kill yourself that was big big advance there is of course some reason to think that some small ish or small percentage of individuals have very strange and strong reactions to some of the modern medicines the the SSRIs and so on strange and strong and there's some reason to think although it's a bit of a needle than a haystack problem some reason to think that there that they can be responsible for rather extreme behavior that includes suicide strong suicidal ideally suicidal thinking and also homicidal thinking and possibly even a greater incidence of that but at the same time the there also for many other people reducing depressive symptoms and thereby reducing suicidal thinking so it's a very tough thing if you will it's a kind of an epidemiologists nightmare because or actually that's what they do right they love these kinds of problems but it has these different kinds of things that can be confounding but certainly enough to have us worry and some people very strongly are convinced that they're these medicines have that effect on some individuals and certain especially on adolescents okay so all of these medicines though is as many as many differences that there might be they tend to have produced about a 15 to 25 increment and response rates relative to pill placebo so sixty percent versus forty percent is a you know it all depends on which study or which sets the studies where you set your thresholds but it's not a bad thing to summarize it as 60 percent respond to the medicine in situations where placebos are also given where forty percent do but I want to emphasize that this is in the patient populations on which they generally have been tested and that'll be comin portent in a few minutes okay so there are also evidence-based psychological treatments for depression I'm going to talk really to the extent I'm going to talk about these and we talked about cognitive therapy it's the one that is the most extensive researched and most well maybe most widely practice as Martha was mentioning it compares favorably and its outcomes with antidepressant medications you'll see these abbreviations throughout so CT and ADM for cognitive therapy and depressant medication even in the Morse even in more severe cases of depression and it's the only treatment that we have that where there's substantial research evidence suggesting that when you stop taking the treatment you are protected to some extent against relapse once you're done so that's we certainly don't have any reason to believe that that would be true in with medications and there's no evidence to suggest that it does and there's no other psychological treatment that has that kind of body of evidence so it makes people interested in this as a as a treatment in a personal therapy given time I'll just I just want to mention there has been some research done on it and then there's the new one behavioral activation which was just becoming popular when Tom Insel the director of the NIH decided that we know everything we need to know about treatments for depression and so we can't study this stuff anymore so excellent results in two clinical trials and evidently we're done so but it's an intriguing treatment that to some eyes appears simpler than the cognitive therapy does and therefore possibly easier to disseminate but that's all sort of what seems to be possibly so rather than anything that anyone's tested you might detect that we tried to submit a grant on this question and we're denied we were not allowed to submit the grant so after doing the work that you'll see in a minute here are just some some facts about how antidepressant medications are being used today this is these data are now you know five plus years old but they're they're probably quite representative of what's going on now so if you take teenagers on up eleven percent of Americans are on antidepressant medications you probably have seen these figures by now they among those if you survey all the people without symptoms for depression eight percent of them will be on antidepressants now of course some of those would might tell you and maybe even correctly that the reason they don't have symptoms is because they're on antidepressants nineteen percent of those around with mild symptoms are on them twenty-eight percent moderate 33 percent severe so you know there is a lot of this is being used and we don't really know in you know in the kind of sense that we would like to know how useful these things are for people so obviously if if you find people who are in severe who have severe symptoms 33% of our medications you might say good they need to be on them but then they still have severe symptoms and and so I'm not giving you any definitive answers here I'm just saying that this is a common treatment that we don't think very much I don't think we think very carefully about is I'll keep as I'll be talking about as we continued of all those on antidepressant medications 60% of them which would be 7% of the population have been on them for two or more years 14% of them have been on them for 10 or more years so pretty you know chronic use and less than a third of those on a single antidepressant medication so let's finish the sentence less than a third of those on single medication have seen a mental health professional in the past year and less than half of those on two or more antidepressants so polypharmacy less than half of those individuals have seen a mental health professional in the past year this is in the u.s. they're being used as you probably know for lots of things for good or ill for pre mental tension for sleep disturbances migraines feeling tired so National trans e's are now these data are bit old now but but they illustrate a point really that continues namely that about those among those people diagnosed with depression the antidepressant use increased and it really did make a huge increase in this period 35% were being treated with antidepressants in 87 as Prozac and so on was starting to be known and popularized and by 97 more than double that again of those with depression that is that a good thing or a bad thing that's that's that still is a good question psychotherapy at the same time though was B was on a decline in terms of its use for people with depression so it became you might say this is a reading that says that in the popin in our population and among health professionals the belief in that period was antidepressant medications good psychotherapy not so good and or certainly not as useful and again the trend just widens a bit but that's where the knee and the curve occurred so the reasons for the trends over time and this is kind of this is where it gets I think a little bit more interesting so I loaded to the fact that the SSRIs that they're safe to give primary care providers can give them without fear that there well with tiny bit of here that their patient will go home and kill themselves they won't kill themselves with the SSRIs but there is this a concern about inducing that kind of thinking but at any rate patients don't complain about the much relative to other medications the federal government in partnership with the National Association mentally ill it really went decided this was an important public health problem which it is and embarked on a public health campaign to educate the public about depression a lot of this was distinct depression which i think is generally a good thing I think there are some not-so-good things that happen in the midst of that and you may know what I mean we'll get to that later too promotion of sales through vigorous advertising campaigns to primary care doctors and to consumers we all know at least those of you are in the united states and though that that it's very hard to go a day without actually you can do it right you just don't watch TV don't listen to radio yeah you can get a day without seeing these ads keep your pop up yeah that's right get a good pop-up blocker so at any rate the these these campaigns certainly were effective and the growth of managed care and these by the way these are Olsen's conclusions I've got some things to add to this but growth of managed care resulted in shifts from specialty to primary care medical management so it's I could think I think I heard on John you were talking a little bit about how hard it is I mean there are all kinds of issues including like Who am I going to refer this person to even if I think it's a good idea and will they show up if I do refer them that's another problem but psychotherapy certainly has reimbursed less generously than medication treatment and primary care physicians for a variety of reasons of course are using medications Lorenzo and I are partnering with a colleague here at Penn to study the the beliefs and practices of prime primary care providers and in discussion some of that those data might come up okay so 80% of prescriptions are made of entered precedents are made by physicians who are not psychiatrists okay so in other words and 62 percent most of those in other words most of the those who aren't psychiatrists are primary care providers and antidepressants are increasingly being prescribed for not just on diagnosis as in not yet diagnosed conditions but in conditions that would not meet the criterion for certainly major depressive disorder but a good chunk of those would not meet criterion for any mental disorder but again we mentioned fatigue sleep and other kinds of reasons people are being prescribed these medicines so again primary care providers very important in all of this they treat at least half of the depression cases a lot of people in primary care who go to see their doctors there's a there's a course of bias too for people to go to doctors when they're not feeling well in general they're having health issues and there and they may very often they will also if asked or even if not asked will describe a condition that could meet criterion for depression and most people when you in this country when you survey them when you ask where would you like to go with the mental health problem they'd say I want to go to my doctor meaning my primary care doctor they don't want to go to some shrink they don't want to go to you know some some psychotherapists they've you know they want to go to their doctor okay Americans attitudes it kind of goes along the same way this is just again a trend that where the knee and the curve was right around the the turn of the millennium so we see 98 to 2006 you see that an increase in the percentage of patients although already pretty high that that think medications can help people feel better about themselves that's the way it's worded helped me deal with day to day stresses okay a medicine that helps it so now we're talking I think enhancement when you frame it that way help me deal with day to day stresses that sounds like enhancement to me it's kind of a negative spin on enhancement I guess it's but still and then 47 would take medications to cope with life stresses and that's a little bit different right but it's a little different frame because they're implied is may be a big stress as opposed to the middle one where people are saying yeah they can help with day to day stresses again none of this is good or bad and that you folks wouldn't be here if you weren't of a mind to be able to think about things that is not black and white not good or bad and I'm I'm not going to try to push you into thinking black or white except on a couple of things of course so so why has a psychotherapy the use of psychotherapy reduced over time particularly since awareness is bigger and so on about mental health problems so there really hasn't been public education about the effectiveness of psychotherapy so you don't see ads for these things and these these avid advocacy groups National Alliance for the mentally ill and so on they tend to be people who are very much involved with very severe mental illness but also they're getting funding from the pharmaceutical industry that's I mean they've got to get funding somewhere to get their message out so they've partnered with them and we know what can happen even when we're not looking or not paying attention when when we partner with someone no even if everyone has good intentions lack of availability this is what an John was at least in part referencing if I heard correctly in the hallway so they're really just aren't people trained up to do this kind of to do an evidence based psychotherapy there is a persistence of the belief that psychotherapy is more expensive than medication it's and and we can talk about I mean I think it's certainly not a given that that's true and in fact I'll show you some data that suggests that it's absolutely not true or that the opposite is so at least under certain assumptions and then consumer demand for Ana depressants is just Avedon again patients come in and they expect to be treated with antidepressants antidepressants they know that if they get a prescription they can go down and fill it and they'll pay two bucks or five bucks or whatever the copay is that's pretty good it doesn't mean that that's the cost of the medication that means what's coming out of their pocket at that moment and of course when I met more than I just meant to say which is it's coming out of their pocket at that moment then it's going to come out of their pocket it's a few months from now and a few months from now in a few months you know so 10 plus years of a few bucks out of your pocket even the co-pays add up but certainly the the retail cost is it's quite high can be and also and this is you know consumers are thinking wait a minute so I can go to the pharmacy once or maybe go for refills and it paste something or I can show up once a week for 10 20 weeks go to somebody's office downtown you know it takes time it takes I've got arranged who's going to watch the kids and that kind of thing and they're gonna make me talk about stuff that I don't I'm not even good talking about with my husband or wife much less some stranger alright okay so have the shifts in treatment practices yielded greater benefits the increase in treatment generally and particularly the increase in the use of antidepressants well by all accounts the rates of depression and the chronicity of depression and the disability from depression all continue to rise we could debate the the the data there there it's very hard to get data that are as clean as a whistle on any of this over time but but certainly all of all things point to that to those facts relapse rates on the most common treatments are as high as 50 to 80 percent so that's not a a great selling point lifelong treatment is recommended for patients with recurrent depression so you know if you're gonna be in treatment for the rest of your life all kinds of issues there aside from the high cost of course there's the anything that develops over time medically from those you have to worry about patients often this this is a point that's I I went like this many times smack myself in the head when I read Robert Whitaker's excellent book that I'll reference a bit later on that clinical trials are set up this way too so patients who go off their medicines if they're on an impressing learn that the medicine was good right because they start to feel really bad so and you you know you think that that that's the a reasonable inference and moreover compared to people so you if you go on to placebo the same thing relative to few stay on medications so people who are taking off their placebos do worse in the period of time that they're being watched typically than the people who stay on their medicines well that would seem to show that the medicines were doing their job and it might and it might even for some subsets and so on but what it could also show and what we know that to some extent it must also show is that the people are being taken off their medicines are feeling worse because they're being taken off their medicines because they're having what what's called a discontinuation syndrome that I've been in pharmaceutical reps talks where this the someone jokingly mentioned withdrawal effects oh no no it's not withdrawal its discontinuation it's a big distinction there so the discontinuation syndrome and for some of the more modern medicines you may know this the discontinuation syndrome can be extremely unpleasant for some individuals and and it usually isn't a whole lot of fun so why haven't we developed it why why are we here why are we 50 years in after these great discoveries in the 50s of these medicines that clearly have an effect on something that we care about the the Mao is and then the TCA is and so on why why are all these things true 50 years later why not more advances well there are many ways to answer that question one of the one of the answer is that clinical trials focus on a certain thing and I mentioned before that some of us have followed the pharmaceutical industry and the design of art psychotherapy trials and you'll see that here but we were actually I don't wanna say force that seems too strong we were strong-armed that's better into doing our trial on only the more severely depressed patients our big trial that we did around the turn of the century or that we published in 2005 I'll show you data from the idea was no no the the people with greatest interest are those with high severity symptoms those that's real depression and there's a point to that but it turns out that lots of points to that and one of those is that the Beth is the group that had been studied by in the pharmaceutical trials because it was understood but that was the group that was most likely to reveal a difference between the medicine in the control treatment and there might be other good reasons to study the more severely depressed patients and their the reasons we were willing to alter our our own research in order to focus on these more severe cases but what's happened of course in the interim is that most of the people who get treated for depression are not in this group and so we've kind of don't know very much about the group who are getting most of the treatment okay this is just a slide to show you this is a Martha reference some work that we've done this was this is an update of a what we call a mega analysis or we can just call it a mega meta-analysis in polite company but this is published in the American Journal of Psychiatry we were quite surprised that the that Journal would take this paper but they did and and the bottom line was that everyone in the field was talking about these 53 patients who produced in this study that was published in the in the early 90s these 53 patients who produced this result which was that a in the subset of patients in this study who got either cut randomized to cognitive therapy antidepressant medications the ones in cognitive therapy didn't do very well this is higher is worse worse scores and Hamilton depression scale and the ones who got in their present medications you know did better than that okay so we've we said or so as well there are other data that people haven't looked at in this way of dividing into more severe and less severe and when we did that we find and we continue to find I mean this is just a this seems to just be so that when you compare even in this more severely depressed half if you will or of the population and press people you just pretty much find in the short run that these two treatments antidepressant medications and cognitive therapy are about equally likely or weakly effective to in reducing symptoms Martha referenced that there might be some advantages and I actually said something about this a few minutes ago – this is from that study that we did that assign people randomly to cognitive therapy versus medications and then at the end of the 60 we treatment only those who had responded to cognitive therapy and medication turned out it was a 58 percent response rate in each case we then tracked them over the next two years this is this shows the first year of data and over the first year those who had been on medications were randomly assigned to either stay on their medication that's the red group or to come off on to placebo that's the yellow and these are the people in cognitive therapy who the blue ones who were then could see it they basically were finished with therapy they could have three booster sessions in their year if they wanted well what you can see is and these are relapses so it's a survival curve and cognitive therapies patients were protected certainly relative to those with short-term medications namely put onto placebo and at least numerically superior not statistically significantly so relative to those who stayed on their medications and this is just a summary of that in a way which is something we should care more about isn't how many people get better and if you only care about relapses then you've left how many people get better behind and so this just collapses those two indicators that getting better and the staying better into one index and so this is the we're still not doing great but what we're certainly seeing here is not doing great with short-term medications a bit better with medications sustained for 16 months and a bit better yet with cognitive therapy but cognitive therapy happening pretty much in the first four months this is just one analysis of cost and it's just at this point it's schematic is an older slide that these are in Euros R so I know I don't know what they're in no they're in dollars but in not in 2013 dollars and basically the point is that and these these are actually drawn from data at the time that the medication that costs if you people on medication keep rising and at a certain point and in our data that point was crossed twelve months into treatment the cost of the medicine provision actually begins to exceed the cost of the COG therapy and this again was in the context of cognitive therapy doing at least as well in to treating the symptoms and keeping them away so again I guess I asked the question this freight I used this phrase earlier how do we get here so in the 50s there was a great excitement about the prospect of understanding and treating severe real depression by identifying an altering crucial but I think we always thought would be simple brain mechanisms these big motivation I mentioned expansion of the definition of depression we're going to have a look at that now and in the introduction of Prozac and then promotion of antidepressant medication so I guess we've really covered those things but here's what people who take antidepressant medications will tell you and they believe it and we I can't tell them that they're wrong I shouldn't tell them that they're wrong first of all people who take counted the precedents will say who's great it helped me throw my depression I have no doubt that for if we could somehow run the experiment but the time machine you know the run and parallel universe for many many people that is just absolutely so there are other positive effects that these medicines have on people that they're they'll talk about and they don't really care I mean somebody who's taking medicine doesn't really care if their depression score is going down if they care about whether they like the way they feel more and it might not be that their depression scores going down it might be other things we have some data on that too there certainly are placebo effects that the person who's telling you about this has no idea how much it might be affecting him or her but we know that they are there in general in the aggregate and then of course there is this discontinuation effect so people say oh no no no but I know my depression I need my antidepressant because when I started to go off it I felt awful therefore I am a person who's better with it well we don't know that you would have felt awful this month if you'd never started taking it I mean that's in that's the point so so treatment of depression moved to primary care providers and patient demand increased and then somebody said or two guys actually said wait a minute let's take a step back and ask ourselves what we're doing so I recommend this book to highly that's a proper phrase I think that you can twist that one but you know what I mean I really recommend this book and it is the book called the loss of sadness how many of you have either how many of you have seen this book or know about its existence okay so loss of sadness how psychiatry transform nor normal sorrow into depressive disorder and what's so impressive about these two guys is that every time you think that you're gonna say oh there's oversimplifying or that you know no this is not oversimplified this is I will try to convince you of that or at least try to convince you to look further into it and to find out for yourselves that this is not an oversimplification and to get to a bit to the punchline they're not talking about we shouldn't treat people they're not talking about that there isn't real depression and so on they're talking about something else so what they want to emphasize is that sadness is a universal emotion that's cross-cultural present animals so it's it's it seems it seems I mean you can't quite argue from this but it does seem that that we're kind of built to have at least sadness there there there's as it were well maybe not no getting around it maybe there's some enhancing drug that makes it so we never need to be sad but at any rate it's been around for a long time there are certainly we can certainly think in terms of a loss response as having some functions maybe we don't need to get into an evolutionary psychology discussion we can later if we want but there are all kinds of reasons to think that there are mechanisms that we have built in that probably most of the time do very little harm and maybe our actually showed that we're a proper member of the species that are that are organs including this one are working the way they're they're actually as if you were suppose to certainly sadness does have biological correlates we can you you can get people you people don't have to be depressed in order to find cortisol and other kinds of indexes that would say that sadness involves the body of the brain and sadness tends to remit with the recovery of loss of the passage of time so what's major depressive disorder well it's long been recognized in its infliction it's a terrific history in this book that shows how depression has been thought about I've taught about depression for thirty years and there are many many things in this book that I'd never gotten around to reading about in terms of the history of thinking on depression cross-cultural just over and over again the in cultures there is a recognition that there is an affliction there's a serious problem that we that called melancholia depression or whatever and it as it happens though major depression and this I've known for a long time almost well not only eighty five percent there's the number usually happens in reaction to a stressor but it's seen as dysfunctional okay so a what what they would Horowitz in Wakefield would say is that when we want to use a disorder language it it's okay it can often occur in response to a stressor but the key is that it's a dysfunctional response to the stress or not an expected expectable understandable one again we know depression has biological cĆ³rdova correlates and we know it can spontaneously remit so it's a it's a subtle matter to be thinking about to be thinking about this distinction but it's going to get a bit less subtle in a few minutes so according to DSM for the periods of sadness are inherent aspects of the human experience these should not be diagnosed as major depressive disorder criteria and major depressive disorder unless criteria are met for severity duration distress or impairment well yeah except that once you get these you're gonna get this I mean this that's the the depression is about distress so if you have some symptoms so this is an on this is not a useful criterion if people are distressed they're in distress the but it the point being that this just distracts us for whether that distress or or even impairment is something that we need to or should whether it's useful to think about it as pathological as opposed to something that that is distinct from the pathological okay well how many of you have heard of Robert Spitzer okay sobre Spitzer was the primary architect a leader in the development of DSM 3 and and he seemed you know what he laid out in the logic for that seemed compelling at the time so I'm not gonna second-guess it it was how I was trained it made good sense he wrote the the foreword a lengthy forward to this book in which oh this is the Robert Spitzer and I'm gonna get this a little bit wrong I'm sure you guys know this but this is the Robert Spitzer who had to retreat from his position on homosexuality as a disorder right so he has done this before and I actually respect him for the willingness to retreat it always better to be right the first time but better to be right eventually so he wrote a lengthy preface to the book the DSM is not consistent even on applying its own definition of mental disorder to the diagnostic criteria sets specific for specific disorders see what that is in a minute so all right so the what's what is the loss of sadness means it means of course the loss of our ability to appreciate that sadness is a thing is it on its own is it and it's okay and is normal as it were it's an adaptive loss response we can think of it say and where as major depression should involve a dysfunction of the normal lost responses or in some cases as you know depression it doesn't even appear to be in reaction to a loss at all it just looks like a lost response but it may occur if you will seemingly at least that loud of the blue symptoms of major depressive disorder can occur in this way of thinking about it the symptoms can occur in response to a life stressor and without being indicative of dysfunction in fact might indicate function and by ignoring the context in which symptoms occur DSM confuses sadness with major depressive disorder so this is just a case that's from the book and and let's read it it's because we're all here so a 64 year old married man has developed feelings of sadness and emptiness lack of pleasure and activities insomnia fatigue and lack of energy and feelings of worthlessness so there you have it the depressive symptoms he's not interested in seeing friends and seems unable to concentrate on anything he yells at his wife when she attempts to console him and rejects her efforts to comfort him I mean this is certainly painful distressing and disabling or you know dysfunction he's not getting along with his wife he's not seeing his friends so this is a problem everyone would see this this is not good in some sense okay well now we can consider that the feelings were triggered two weeks before when the company the man worked for unexpectedly fired him as part of a corporate downsizing just six months before he would have qualified for the company's retirement plan one of the major reasons the man chose to work for the company and then spend two decades with it had been the prospect of generous retirement benefits the loss of these benefits means that he and his wife will have very little retirement income other than Social Security so you know it's not just that he lost the joint you can imagine I mean in fact what I like to do is to think of the opposite I like to think of a person to whom this would happen and they go and they say well you know that's life and then it's I mean that that's a no that's a response to this but I'm not sure we would all say it is the one and only best response to this I mean here is certainly we I hope you would forgive me if this happened to me and I said oh my god I can't believe I did all this planning what an idiot I was to do all this planning based on all these assumptions that were you know so this is what's happening to this guy in there in the aftermath of this so subsequently the couple is forced to sell their house and move to a small apartment the man finds part-time work that along with Social Security provides barely enough resources to sustain him and his wife so the the problem sort of persists I mean the bulk of them do he remains bitter about how he was treated but his symptoms gradually subside over time now in one way of thinking about this this part this guy went through a major depressive illness episode okay and then there's the other way of thinking about this which is that his brain mind person worked in the way that people's brains minds and persons do and it did to call this disorder would be a disservice or creates problems so so the proposal from the loss of sadness is that the and we have someone who's kind of has sadness the context is specific to losses it's proportional and and this is the important thing you want to pay attention to the conjunctions and disjunctions here so proportional in intensity and duration okay so that implies if it's not proportional okay and it wanes with time and changes in circumstances in circumstances and changes in internal coping major depression in this way of thinking about things occurs out of the blue or at least well occurs out of the book or is disproportion in intensity and duration in cognitive and affective ways or persists despite changes in circumstances of the passage of time so for example in the case we just looked at the one case sweet wee-wee bread if that individual in that new context in which he was doing okay if he continued to have major depressive disorder symptomatology even in this way of thinking about things we might say yes the person has now developed a major depressive disorder we now can say because the the reaction was disproportionate in time and and and relative to circumstances that would have that one might be a tough call but it would depend on how well the the he was getting along whether he was able to at least pay the rent and so on but that's the assumption so I don't know how many of you have spent much time thinking about classification of oppression I used to think about it a lot and I actually still do and there's lots and lots of work on trying to find subcategories of depression that carve it up because depression is a heterogeneous even or Horowitz in Wakefield and endogenous versus reactive is a big one but this is not that revisited there's a different assumption about the role of life events so in the old system the people were trying to help make sure everything lined up so endogenous meant no life events triggered it it meant certain sets of symptoms including waking up too early rather than having trouble going to sleep for example not eating rather than eating too much so there were all these desires to have course symptoms triggers and so on line up in a particular way and this the way I'm talking about here and that you can read more about with the book it doesn't make all of those assumptions and I think that's only to my reading it's only a good thing it's nice to have these two streams that are different in every way but that's probably not how it works and also there was an assumption about treatment response that if you have a real depression endogenous when you're going to respond very well to medications and if you don't you won't and if you have a reactive condition you're going to respond to let's say psychotherapy and if you don't you won't well none of that has panned out and it's not surprising that it would and I'll just say one thing about that there's nothing in this way of thinking about things that would say that even if the guy they didn't make that phone call and someone gave him a medication there's nothing in that that says he won't start to feel better right he could feel better and again you all can think of it in terms of enhancement kinds of thinking if you want so there's there really is it'd be nice if it all lined up sort of nice be simple anyway but no no need for it to do so if we want to understand how humans function how to make help that help them function better so there are many reasons to think that it's that it'd be important to get it right obviously it's tough to figure out the neuroscience of depression if you're studying depression and something that's not it's tough to by the same logic it's tough to figure out the ideology genetics or any other kinds of an ideology about a disorder if you're studying if you're putting this fellow in assuming certain things about this along with individuals who have these courses of depression where they simply are having dysfunctional reactions to things obviously it leads to what can be unnecessary treatment and we find and we get miss estimates of prevalence rates now I guess we're I guess my my talking time is basically up I want to mention something that I'm sure you've all read about and thought about and that is the bereavement exclusion and Jerry Wakefield one of the authors of the book has been very involved in in discussions shall we say with those at the dsm-5 and to just give a bit of background the the idea is that in the last 30 years if you had all the symptoms of depression but it was understood that and in they lasted for two weeks it was understood that you had lost a loved one your spouse in the previous six months they've changed the timeframe at various times but let's say six months you would not be given the diagnosis of major depressive disorder you because it'd be excluded for breathing and there so that that could be a useful way to do things but there are two very different ways of doing it than that the one way that the DSM has gone most recently is to say wait a minute there's nothing special about bereavement if you're depressed you're depressed we have to take that seriously if you're not fun you know you've got all the symptoms there's it you are you have major depressive disorder that's one way and you could say well the fight would be between those who want to save bereavement as an exclusion versus those who want to say no no it's nothing special well Jerry Wakefield is over here he's saying there never was anything special about bereavement but there is something special about having losses and things that people react normally with sadness and so on – so there that and – just to keep it short and you'll know what I mean the the recommendation is that there be a loss and expectable circumstance in the in the face of expectable circumstances exclusion which would capture a lotmore individuals including by the way and this will cut it off here including many individuals who already mental health professionals are giving the bereavement exclusion – even though they're not in bereavement it's just that the the mental health professional will write down this bereavement even if the person was fired or a person you know dog died or which for many of course is even worse than the spouse nine and and so on and so so that's where things are but if you've you know you've read about it in the news all the dsm-5 stuff but in the depression world this is the one that's that has taken up the the attention and it really unfortunately in the news this kind of discussion I don't think has been featured much so it really has been should bereavement be excluded or not as opposed to should we be thinking about the fact that people can be sad and think about that differently than that they have a an illness disorder what-have-you so there there is plenty to discuss and I think that's but I think there's plenty that I've already shown you that that should lead to some discussions so I'll stop right there and look forward to learning from you

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