Full episode transcript below. Beware of typos!
David Cohen 4:30
Discussing the way I approached drugs as a kind of a lifecycle approach or even a biographical approach that is drugs as as living creatures that move through time and space in a way. So there's that, you know, it's a way to look at drugs of all kinds. And I put both the licit the you know like psychedelics and and the the anti psychotics I put them all in the same ecology. They're all substances some we call psychoactive some were not Sure, and but they're all in the same ecology for me. And so I like to focus on the language we use, how we talk about things, which makes it seem like they're really different things, but they're not quite different. So just, maybe we get into some of these broader issues.
Nick Jikomes 5:16
Absolutely do you want to just start off by just telling everyone who you are and what your background is?
David Cohen 5:23
I'd love to so my name is David Cohen. And I am, I'm an adult, I'm from the planet. I was born and raised in Morocco, North Africa. And, and I moved to Canada when I was about 11 years old, and then spent a couple of decades at least in Canada, and then eventually have been living in the United States in different parts of the United States. And I've traveled around the world and lived in many parts of the world also. And I am a professor at the University of California at Los Angeles at the Luskin School of Public Affairs. And my background is as a clinical social worker, originally, who then got started to study drugs, medications, as they were called, or they are called, specifically prescribed psychiatric, or psychotropic medications, and their effects on people, on my clients on and then their history. I often wonder about how do you how do you understand, say, a person, so you want to know what happened to them where they're coming from. And same thing with drugs. So I got into very interested in the history of drugs and where these things coming from what have they been through what's happened to them over time, and over to the same substance, so group of substances. And so all of this led me to both from kind of a sociological, medical, chemical, anthropological economic point of view, to study, both illicit drugs and the illicit drugs. And I've been to school, I got a PhD in, in social welfare at from the University of California at Berkeley, in the early 90s, studying how the anti psychotic drugs helped, or didn't help, the sort of social integration of people that had been institutionalized for decades previously, and were then sort of thrown out into the communities and what drugs did to them whether they made a difference, and in what way, so that was something that I focused in a lot, and then moved into the different classes of prescribed drugs of benzodiazepines, then widely and still today, given to older people, the antipsychotics given to anything that moves in an institution. And then the drugs that were emerging then in the 80s, and earlier for children that stimulants and, and the rise of the age, ADHD phenomenon, and how that then move to ADHD and to adults, and then how how drugs played to that the drugs start the phenomenon, where drugs are response to the phenomenon, that both things move at the same time, and how each fed the other. And I've sort of gotten wider in terms of the perspective, looking at different countries, looking at how things are emphasized in different countries, especially with respect to children, in terms of countries that don't medicate so much, educate a bit more, take care of families more, rather than focus on what's going on in the brain of that four year old. And so, and seeing what the outcomes might be, whether we're doing better, they're doing better, et cetera. So touched a lot of things. I love what I do happy to be here and talk.
Nick Jikomes 8:57
Excellent, ya know, you've got an interesting background. And you know, even on this podcast, we often get fixated on sort of the internal mechanics of these things, how are drugs affecting the brain and how are they working and all of that's very interesting, but your background sort of gives you a more holistic picture of how drugs and people are interacting at you know, multiple levels of analysis, you know, how is it actually impacting the people? How are how are sociological and and other factors interacting with the medical and the scientific side of this to get just get some terms in people's heads? Can you start off by just defining like, what is a psychoactive drug? And what is the psychiatric drug? And when do those things overlap and where are their differences?
David Cohen 9:43
So let's say that a psychoactive drug, which probably would be the the oldest term of the two definitely would say, a psychoactive drug is generally defined as something that change changes your mood. changes how you feel changes how you think changes how you behave. Others then add add to that definition. It does all these things by acting on your brain. That is by you injecting, ingesting the substance. It interacts with you at a molecular level. So it acts on your matter if you will. And as a result of that direct material action, it then has sort of a reverberation of effects on your thinking, feeling being. So that's generally a psychoactive drug. Some people just say, it changes how you think you feel you act. That's it. They don't say how it does that. They don't necessarily by that it, does it buy that direct material action, they might think, well, you know, if you think you're taking something which is going to affect you in a certain way, then you're going to have the effect even though you've been giving an inert substance, a so called placebo. So it's not sure whether that direct action on on your you know, molecules, or you say your receptor systems, is what caused you to change how you think or caused you to feel better, or cause you to fall asleep. So the exact manner of action, what you call the mechanics, is not necessarily part of the definition of psychoactive, just a generic term to say, it appears to change your feelings, you're minding, and you're behaving. Psychiatric Drugs are a subset, as you can tell, it's not so much. They're not so much a particular kind of matter, particular kind of substance. They are just used. They're part of the Pharmacopoeia of, you know, of different substances that happened to be used in psychiatry, originally. And then, of course, spread to all sorts of other medical disciplines. And so psychiatric drugs are also considered psychoactive. Because the things that psychiatrists let's say you're more interested in in doing is changing how you feel you think, and you act. And so the traditional psychoactive substances, like say, alcohol, with a traditional early medicines, and opium, so things that could easily be shown or seen or experienced by people to put you to sleep, to make you happier, to stop you from feeling pain, and so forth. These were the early medicines that were used in psychiatry early on. And still today, alcohol is a big component of many substances that are prescribed. And so they're called psychiatric drugs. When did those get a big boom, starting around the 50s, and 1950s. But also earlier, we had a number of them, but around the 50s, you have a sort of serendipitous kind of discovery, falling upon read refining older substances that appear to be useful for the problems facing psychiatry then, which is how do you manage half a million people in institutions? All kinds of people, upset people, sad people, lost people to place people, senile people abandoned people, criminals, how do you manage them when they're under lock and key, and you don't want to kill them? So that's the problem that a lot of psychiatric drugs solved when they became popular at first, later, as the patients move, the drugs moved with them. And then they began to spread out much more in the community. And then they we found other uses for them too. So so that's a general I don't know if that makes any sense to you. If you find yourself in those definitions. Or if you want me to get into you know, what are the classes of psychiatric drugs today? The major ones?
Nick Jikomes 14:18
Yeah, no, I think that makes sense. psychoactive psychoactive drugs, just any drug that affects the way that you think or that you feel or you behave. It has some sort of impact on you know, the way that you're conducting yourself and your conscious experience in the world. A psychiatric drug is defined based on its medical utility. It's a drug, which is used to treat a psychiatric disorder or set of symptoms of some kind. And one thing that you said. Now, one thing that you said was interesting that I'd love for you to riff on a little bit is in a psychiatric drugs started to become more widely used in the 1950s to help manage people that were in institutions, not necessarily because they had a disease. These per se, like schizophrenia, although that was certainly one example of how they were used. But just because you know, they were old and senile. And so can you talk a little bit about why psychiatric drugs were originally used with an emphasis on, you know, how much of it was to try and treat or cure disease? And how much of it was to just help people become more manageable in the hands of the people that had to care for them?
David Cohen 15:26
So in your soul in the question, you're asking about the the early uses of the psychiatric drugs, or at least early uses of psychoactive drugs that were not necessarily known to have a future. They were tried. And then they saw that the observers making those trials saw that, oh, this can be useful for us. And then they became, you know, blockbusters, if you will. And that's the case with you know, that classic drug chlorpromazine or Thorazine, which was the you know, first 1953 1954, first used in Montreal, Quebec, in the Verdun Protestant hospital and then brought to the United States, because the person who first used it said, it's amazing, the effects are just like those of a lobotomy. So this is something intriguing. Why would that intrigue them? Because the lobotomy was what people used, they use that to manage people and to presumably, change something in their brain that would short circuit the undesirable conduct they being. So the analogy to something very, that we consider today kind of drastic way of behavior control. That's what inspired people to continue looking at Corporal muzzin. It made people extremely passive. And so that's an end. Why did they do that? Why were drugs actually given to these people also? Well, because the people taking care of them were physicians, they assumed these are diseases, but they had like today, we don't have or they did not have like today, we still don't have proof that these are diseases, they treated them like diseases. They assumed they were diseases, genetic based on bad habits, families acquired because of alcoholism, et cetera. And they had to be treated. But it wasn't always thought that it that this is what the problem was. And it might not always be thought of that in the future. So what I'm saying is, they had to manage people. Drugs is something that whoever we're supplying them with products and ideas, and other researchers said, Hey, this could be useful. Look, I see that these rats who were fed the urine of other rats that have been taking lithium, these rats become very lethargic. I wonder if we could use that with people in mental institutions. Or this person says, I see that this person deficits operation being given a little of the substance called chlorpromazine, they are so sedated, and so quiet, you can do with them what you want. I wonder if my colleague in the psychiatric department might find that useful to manage his patients. So this is how the drugs actually spread in the 50s. And as they were useful, then in those institutional contexts, then people thought, well, maybe they could be useful for other things. And then you know, in a way the drugs spread. And while this was happening in us in the institutions, you had other drugs, which we consider today psychiatric drugs, which were mainly used outside the institution. The main examples were first the barbiturates, then the benzodiazepines. And before that the stimulants, those had a long and respected history before in the public, among housewives, airline pilots, soldiers and warriors, and people who just wanted to sleep. Outside the asylum. These were already used and widely prescribed to millions of people. And they continued their way, their parallel path, eventually, they mixed with mainly the anti psychotics, and the antidepressants that were originally conceived for use inside the asylum with institutionalized patients, you could call them, many of them were basically inmates. So I don't know if that's answering the question. Or if I just went off on some other some other tangent?
Nick Jikomes 19:45
No, no, I think that that does start to provide some good historical context here. And maybe we'll fill in some of the historical gaps as we go on, but sort of jumping to the present day. You know, I think most people listening will know that, you know, psyche. Trick medications are widely widely prescribed today, probably more than they ever have been. And there's a variety of classes that are used. And you know, there's different ones that have become more and less popular over time. But today, in the US at least, what are the most highly prescribed types of psychiatric drug classes that are being given to adults?
David Cohen 20:23
What's being given to adults is being given to children. There are no more differences like there used to be just 25 years ago today, it's about basically the same thing. The same classes, you've got five classes, hard to tell, which exactly is the most popular, but I would I would name two or three drugs, let's say if I say, Seroquel, that is an anti psychotic drug that is a drug that aims to officially treat the symptoms of psychosis, having false beliefs being agitated, not having a tenuous a good grasp on reality, let's say that's the symptoms of what we call psychosis or schizophrenia, when it's long lasting. And so Seroquel is a major, multi billion dollar a year drug that is used in that category. Why? Why are there so many people that are severely distributed who need it, not necessarily, because it's also prescribed as a sleep aid, as it is an add on to your depression and so forth. In other words, that's called the off label use. It gets studied by in in a regulatory framework for a certain indication it gets an A market approval for that indication. But as soon as it's out there, beyond the fence, it runs wild in the field. And then we start saying, maybe we could try it for this and for this and for that, and younger people and older people in different people, then the condition for which it was first tested and approved for marketing. So Seroquel is a big one. Celexa is another class, that's a brand name I'm giving you and that's an anti depressant drug are called anti depressant. And among the stimulants, you'd have adderall or ritalin, definitely. And among the benzodiazepines, which are tranquilizing sleep inducing very much like alcohol and appeal drugs. You've got probably Klonopin, or Clonazepam, it's generic name, and a couple of others. So I would say those three or four are probably you know, it varies every decade, you've got variation into which is the newest drug in that class, or the one most marketed, so that becomes the most popular, but you've got about So couple of antidepressants, a couple of antipsychotics, and a couple of benzodiazepines. And, of course, you've got also some anti epileptic drugs, which we today call mood stabilizers. We call them mood stabilizers. That's a moniker you know, it's just it's a label to say, it's a marketing. It's a marketing label, we say, well, let's call it that. And let's people think that, oh, there's a mood stabilization that comes in the molecules of the thing. But really, it's just a little word we call them. And we might not call them that two years from now. But those are originally anti epileptic drugs, anti seizure drugs. And for some reason, a couple of names just don't come to me right now. But those can be pretty popular too. So you've always got 10 drugs, among about 100 prescribed psychiatric drugs on the market in the US, about 10 of them will make up 80 to 85% of the whole prescriptions. 10 drugs will be the drugs that are most frequently given to most people from most problems.
Nick Jikomes 23:56
I see. So there's a couple things I want to talk about. I want to talk about some of these specific types of drugs, like the anti depressants and what they're used for and what we know about them. But also something that you handed out was, was the idea that there's a lot of people on multiple kinds of drugs, you might be on an antidepressant and an anti psychotic and so forth, and I definitely want to get to that. So for like some of the antidepressants that are out there that are the most popular are these typically today SSRIs selective serotonin reuptake inhibitors. And you know how and why did those become the most popular type of antidepressant medication?
David Cohen 24:34
Absolutely, yes, they are. The SSRIs are the most prescribed now and they have been for about so we're now about 2022. I would say they've been that for about 25 years. They were introduced in the late 70s. Prozac was the first SSRI marketed in 7990 and 81 or so if I'm not mistaken, and then they quickly took the field by storm. Why would we What else was there before, before you had a category of drugs we used to call tri cyclic antidepressants, which were very similar in chemical structure to the to drugs like chlorpromazine, one of the earlier neuroleptic drugs or anti psychotic drugs, those powerful, you know, stop motion stop initiative type of drugs, modeled on on those drugs were the tri cyclic acts, which were used, like trilla, fawn, or extra fawn and, and, and a number of other drugs that were used mostly within patients who were thought to suffer from severe depression. But what happened was that these drugs were not so satisfactory, because they had a number of adverse effects. People use them a lot to commit suicide. And you had to take him several times a day, they had problems, you know, targeting the distant the gastrointestinal system in ways that were just not desirable. And, and, and also, there was a problem with the benzodiazepine drugs, which were tranquilizers people were using to sleep and to combat anxiety. And those were more observed now to be drugs that were really difficult to quit. People were therefore called, you know, they were addicted, they were dependent, and they had to offer withdrawal symptoms. And so, so the SSRIs came and kind of said, we can really take over the treatment of depression. And we can take over the treatment of anxiety because we have these amazingly safe drugs, like Prozac was marketed as a drug with no side effects, no adverse effects, it was a clean drug, it was marketed that way. And so it took the field by storm, everybody was looking for an alternative for the benzodiazepines. And for the, and as the SSR is became popular, what happened was an enormous marketing of depression, depression was not something that was so discussed before the SSRIs. Sure, it was we had diagnoses of depression, but the real boom, the era of depression begins with the SSRIs, they really create the condition. And in many ways, as we can discuss, they may have influenced the condition more than any other drugs before. And in ways that may not be so cool, because everybody got on to them. But what they what Prozac did, also, Prozac first opened the wall with kids, before kids just were kept on the stimulants. And Prozac was the first not to kids, with a too much thought about it. And once that was done, then the anti psychotics and the mood stabilizers and, and the antidepressants really came rushing along, and the kids are now medicated, like the adults.
Nick Jikomes 28:40
Yeah, can you still say a little bit more about the idea of marketing, the ailment itself? So So you said the SSRIs came on the scene. They were marketed as drugs as sort of clean drugs with a lower side effect profile than the tricep clicks. And I think when we often think about drug marketing and the pharmaceutical industry, we're imagining the drugs as the product that gets marketed and they have certain effects they do or do not have certain side effects. But you said something interesting, you said depression sort of become marketed itself and talked about more. What did you mean by that? How does this start to happen? And how do drug companies and other interested entities here market the disorder itself? And how do we think about what's going on there?
David Cohen 29:21
Over Again, fascinating topic to open up. But to answer your question, briefly, how do they market how do drug companies market the drugs the conditions? Well, number one, the main way they do it is they spend a lot of money. They spend more money just on a few psychiatric drugs, two, three categories of psychiatric drugs, more money is spent on advertising, just those two or three categories, then the entire budget of the Food and Drug Administration of the US government. So that by Did the Food and Drug Administration's budget is about $6 billion a year $6 billion a year is peanuts in advertising for just a few classes of psychiatric drugs. I'm not talking about all the 1000s of drugs, that that, you know, humans take, I'm talking just a couple of classes of psychiatric drugs. The advertising budget for those is big to regulate 10s of 1000s of drugs and agricultural products and cosmetics. So that's the first answer, they spend money, they wave the money around. In other words, they use the money to buy power and influence. The money flows over every single aspect of the field. If you say the field is let's call it the mental health field. So state legislatures, there's a lot of lobbying with the state legislatures who write the laws about what will be the drugs on the schedule of what's to be reimbursed. They lobby congressmen and senators at the federal level, they give lots of money to education, they give lots of money to charities, they're a bit like, like the tobacco companies were not so long ago, they have huge budgets, and they spread them in the community. They help everyone, they help medical students, they give bursaries they, they fund 1000s of meetings, they fund journals and studies for their own drugs, which they then submit to the FDA for approval. So I've called it a tsunami. That is, it's like a tsunami of wealth and influence that just rolls over everything, it's big and powerful. And it gets into every little crack. So that you can look there and see, oh, my God, there's industry influence on there, they will fund the continuing education courses for a slew of mental health professionals. And, and I'm just mentioning the basic things Plus, they also give free samples to the physician to introduce into the family or the life of the or the body of the person to begin to. And that's probably the biggest spending on advertising and marketing is free samples. It's not the ads you see on TV, that's actually the smallest, the smallest portion of advertising is that direct to consumer advertising. That, you know, you can go to some channels and you know, in the evening, and there's just one drug out after you or another probably two to 3% of the marketing budget. It's very cheap, to put ads on TV for the drug companies, what's expensive, is to give drugs free samples, and to arrange for so called detail people to come and do face to face lobbying with the physician.
Nick Jikomes 32:47
So until one, what do you exactly mean by free samples? How does the drug company give out free samples? And who and how are those used on
David Cohen 32:55
chests like it sounds in English, it's a free sample given to the physician, right? They're a package of drugs given to them. So they can, you might come in to see your physician. And you might complain if something and you went well, whether it's Zima, or it's a headache, or it's an ingrown, I don't know, toenail. And the physician might say, You know what, we'll talk to you and sending me this and then say, you know, I got a free sample, would you like a free sample? And they give it to them? And say, oh, yeah, that's great. So what's prescribed? Actually, it's free, I don't even have to send to the cycle. It's, and that's the big, that's probably 30% of the estimated costs of the marketing of drugs, or some drugs, at least, is through the actual drugs themselves, being given to the physician to give to the patient, freely. And so that's, that's what I meant.
Nick Jikomes 33:56
Well, I wasn't even quite aware of that that was happening. And that's, you know, I didn't realize certainly that it was there was that magnitude of it happening? Huge,
David Cohen 34:04
huge, billions and billions a year. So the marketing, when the original point was about how a drug and market a condition, it's literally that even the diagnosis when for example, you as a patient might get a diagnosis and you think, you know, this diagnosis, this is my diagnosis. This is what I've got this this is I need to diagnosis from from stepping back. That diagnosis is just it's it's what's been marketed. It's what's been marketed in advance when a drug as it's been shown for the SSRIs for the mood stabilizers, when as part of the marketing strategy of a drug that's coming to the market. The company will often see well how do we promote the drug? You don't you promoted by the diagnosis for which the drug is indicated. So you then all of a sudden have campaigns and citizens groups and celebrities talking about this problem they had, and they were diagnosed with this condition and so forth. And it'd be you you, you begin to make that more popular. And you create a sort of loop where people, you know, placed themselves in that spot to say, I think that's what I got to, I think that's what that's, that's the problem that I got. And if I'm seeking help for it, that's what I'm going to talk about symptoms that I've just seen on that site, and website, it's a test for me to see whether I've got that problem. And now I'm learning what the symptoms are. And so when I go to my doctor, I'm going to tell him those symptoms, because that's what I think I got. And the doctor is going to respond by saying, Oh, but for those symptoms, we have this drug. And in fact, I got a sample here, and it's free. So that you see how that can work. That's an example that I can guarantee you happens every day, 1000s of times every day. So that's how you can market a condition in order to market a drug. And the more the drug is used, the more that feeds into Oh, that condition is serious. That condition is prevalent, more and more people are using that drug for that condition. So then the drug itself is getting marketed. So it's it's it's a broad effort, multipronged, it's backed by almost unlimited resources that's going on every single day. And it's very successful, it's a runaway success. The the drugs are a runaway success today to psychiatric drugs, not in terms of their effectiveness. But in terms of the success of marketing them, despite some serious questions, well documented questions that still arise as to do they really make a difference? And what difference do they really make, to that condition, to your problem, to your life, to your well being? And on and on?
Nick Jikomes 37:15
Yeah, and with that question in mind, you know, when we go from the early days of SSRIs, they were, you know, touted as you know, working, meaning that they helped treat depression, and there was evidence to back that up, and also that they were cleaner that they had a better side effect profile, and lower risk of adverse outcomes compared to some of the earlier generation of antidepressants and other drugs. You know, over the last 25 years or so, as you know, we've had 10s, potentially even hundreds of millions of people use these drugs, sometimes for years or even decades. How is our knowledge of their effectiveness and some of their side effects or potential negative the negative outcomes you might have from long term chronic use? How has that changed? And what are some of those outstanding questions today about what their effectiveness effectiveness actually is? And whether or not they might be actually causing other problems that maybe we weren't aware of, or we didn't want to talk about so much in those early days.
David Cohen 38:11
So when the drugs come to market, and let's take the SSRIs, and you you said, you know, they, we had some evidence at the beginning, that they were effective, and so forth. So there is always some evidence, yes, at the beginning that the drug is effective. But how solid is that evidence? And is it really judged mostly on the basis of what, what's required to put that drug to market? So I just want to, I could discuss that briefly now. Or I could come back to it in terms of, of every drug, every psychiatric drug, after a few years that it's on the market, and we go back, and we get access to the original documents. And the trial documents, which have the FDA to its credit, mostly puts online, quite quite rapidly. So you we can check the trials and how many are there and so forth. And we could see how they were conducted. And in general, there are serious problems as to how these trials are conducted. who conducts them? What are the exact standards by which we say they're working for these people like there is evidence that the SSRIs are helping for depression. So when the drug is not quite been used to long and it's been just tested in a few randomized control trial, shouldn't base trial live that much, then, then then it goes to market and, and so it's not like it's really been tested? So well. There's usually been a couple of trials that either show it's equivalent to the existing drug on the market for that problem. Or it's not worse than that one. And sometimes it's just a single trial that that shows that. So there are questions that are continually arising as we speak like with esketamine, or the drug ketamine that has been put on the market. And the trials are just these withdrawal trials, which I can get into. But they're serious criticisms to whether we can use such kinds of trials, as the basis for deciding that people who are complaining of depression should be on a scatter mean, it would be good thing for them to try that. And which is what happens when it's on the market. So what I'm saying drug on the market is highly, highly questionable. And it shouldn't be taken to mean that it's effective, it should be taken to mean that in the current regulatory context, it's past a certain obstacle course, with some success. Exactly what it has shown is usually in a couple of 100 people, it will make some difference on some highly, highly strained and stretched measure of possibly better functioning. But maybe if you ask the people in the trial, after they finished the drug, are you feeling better, they might say no, but still, those people might be rated as having been improved, because the trials themselves are quite questionable. And there's a whole scholarship around that for the last 20 years, I'll be happy to talk about that. But we don't want to get too distracted. What I mean is drug and reader run. And a lot of resources have been invested to actually make it go through the obstacle course. And now it's, it's used, and again, all these loops are created so that it gets talked about glowingly, we minimize the adverse effects. We didn't even study them Well, at first, we barely studied them, we barely mentioned them. In the in the articles, we mentioned, adverse effects and how to measure them about we give them 1/20 to 1/10, the space that we give talking about the positive effects that we are seeking and how we're measuring those and, and so forth, and we give this fraction of space, in the published studies, to the adverse effects. So just from the start, it's minimized. So we don't really know what it's going to do for people who use it for years, or even for tested for weeks. And we don't know what it's going to do to people who are older or younger, or have a different sex or with different other conditions, because that's not who it was studied on. So I just want to put a big, damp, dampening on this notion that we kind of know what's going on with these drugs when when we're marketing them, and they're effective. We don't we find out later.
Nick Jikomes 43:09
I see. And, you know, with that in mind, for the SSRIs. Let's take as an example. What have we started to find out later. So what have we learned more recently about exactly how effective they are? And maybe what some of the, the effects of long term chronic use are that we simply didn't know or didn't talk about in the earlier days.
David Cohen 43:28
So the first thing that you could say, we found out a lot more was the question of withdrawal effects. So we just didn't talk. It's only because people taking SSRIs is big, and because of the arrival of the Internet, really have web conversations that individual people could write their own product reviews, completely uncensored, and disseminated directly to others without having to go through the voice of the drug company, or the clinician doing the study. They had other interests to promote. Whereas the patient had, again, different interests. And when those uncensored views came out, we began to see that the experience described by many people was not quite the experience described by the official reports. And one of those had to do with the difficulty in quitting or stopping taking some of the SSRIs Paxil was a big one effects or was another one that and Prozac two were drugs that people said had terrible with the depression a little bit that they were being treated for or resemble the anxiety they were treated for with the SSRIs. So that there was always this confusion about well, I've complained to what's happening and my doctor told me that well the reason it's happening to me is because I need to head to take The drug is good for me. So when I stopped taking it, I don't feel good. So I guess I shouldn't be taking it. And so they they take more of it and so prolonged how long they were on it and then worsened the withdrawal symptoms the next time they tried to quit, until we recognize fairly quickly, the mid 90s, you could say already, we had a well described withdrawal syndrome, which resembled very much the withdrawal syndrome, from the benzodiazepines to which the which which got lost in popularity, because of of withdrawal effect. So that's one thing that's emerged. And now almost everybody should know that when you take an SSRI for long enough, or almost any psychoactive drug, actually, you're going away, that will make it difficult for your brain to do without that drug, when you suddenly quit. So that's one problem that's emerged. And it's grab it seriousness, how long it lasts, all of that has been re seen, that has been reevaluated. And it's considered to be much more serious than than we thought it was. But we still can't predict it well, and we still don't know why some people will not have that problem, and why some people will have it in a protracted manner going on for years. One of the first difficulties that was identified as a long lasting problem of SSRI use after you stop it, and even you might have stopped it for months is sexual difficulties, serious sexual difficulties. And so first, it was kind of, well, that's due to your depression, or that's due to something like that. Now, we seem to understand from some experimental tardive sort of late appearing problem that is consistent with the short term effects of antidepressants as libido reducers per profound libido reducers. The SSRIs are, and so that that delayed, late appearing, problems with sexual functioning both in men and women is consistent with that little reducing effect that's seen in the short term. Other problems that are much more rare have been sort of like manic reactions,
kind of psychotic reactions, that image again on withdrawal or appear after some lengthy use sometimes of SSRI antidepressants. Again, the alternative viewpoint says no, these were, these are problems that were uncovered by your antidepressant, your real problem was something else bipolar disorder, action. But the fact remains that, again, with observational, not much experimental evidence, but kind of number of observational studies suggest that, you know, in people that never had any sort of history of anything, either in the family or whatever, and they just hadn't even learned to to sort of be that way these problems would develop, because appear, it appeared because of the use of the antidepressant. So we've got these problems appearing. We don't know what else may be going on at the physiological level. Because we've not studied that very much. We haven't looked at physiological effects of the psychiatric drugs very much over the long term. And in children, especially.
Nick Jikomes 48:35
So you mentioned something interesting, you know, there, there were observations about potential problems that maybe were instigated by the use of, say, an SSRI. But some people took the view that well, actually, no, these were problems that were already there, like latent and the medication sort of uncovered them. So it was that you had depression and you had some sort of bipolar tendency or something. And I imagine that gets you into the realm of doubling up or tripling up on drugs giving someone an SSRI, then you see some of these symptoms come up, and you say, Okay, well, you also need a mood stabilizer or an anti psychotic. So, tell it tell us a little bit more about that. How common has it become over the years to give people multiple classes of psychiatric drugs stacked on top of each other? And what do you think the effects of that have been?
David Cohen 49:23
Well, what a real good question, but that's an astute observation that you're making about, you know, the way that you are going along from the discussion that's used in the field, which is to say that person is on several drugs simultaneously. Technically, there is still some debate about what is it is it two drugs from the same class? So if I give you you know, Valium, and Klonopin, which are both considered benzodiazepines, is that polypharmacy, or I need to give you two different classes, or more than one drug from each of those two different classes. Is it should we start counting at more than one or more than two or more than three. So there is a debate as to what constitutes multiple drug use. But the fact is, and that's been seen over and over again, multiple drug use is worse than single drug use, in looking at almost any outcome measure that we that we try to understand is, especially when it comes to safety. So in terms of safety in terms of the seriousness of an adverse effects that could that could happen in term of urban study together, in terms of, you know, synergistic effects with yet other drugs, all of that raises a serious question as to is this is this something people should be doing taking more than one drug at the same time, especially for a long time. So now, why did this develop as us has to do with, I would say, one of the main things has to do with a diagnostic system, the DSM, which try to somehow dovetail, this renewed and strengthened understanding in psychiatry in the 1980s, that the problems that we were all dealing with were biochemical problems. And those problems could be easily diagnosed by looking at a menu of different symptoms. And, and kind of, you know, taking two of these symptoms, and three of these here, and if you have these five, there you go, you had major depression. Or you haven't one of this, in that section, you had
attention deficit disorder with hyperactivity, rather than with, you know, high with impaired attention, or rather, or it just, you could kind of judge by symptom. And it kind of gave a modular feel, to the person and to the disorder, if you will, and so that when you came in and complained, I'm not sleeping well. And I'm also just ruminating having thoughts of, of of death, then the person would say, you know, we'd look at these two different symptoms and say, Oh, I know a drug for this one. And I know drug for that one. And they've, they're both marketed as safe. I mean, I just met the representative yesterday, and I went to the continuing education course, and I opened the textbook. And they say that these are generally safe and well tolerated by most patients. So I'm going to give you this here. And that'll take care of both the symptoms you're complaining about, I think that general idea which I'm not so much presenting as a caricature, but I'm simplifying it. But I believe it's essentially true. We look at people as having these interacting parts, that I'm treating the symptom, because we don't know the cause. And so I'm going to treat the symptom. And I'll see what the person has to say. And we'll continue if it works, if they're saying, Okay, then we'll continue. If not, we'll try something else. So this is the notion of this leads to multiple drugs. Another thing that leads to drugs I want to continue to make, if I may, is the fact that you take a drug and you're having a negative reaction. And that reaction is not well understood as a drug effect. It's understood as it's just a new emerging problem emits prone sub disorder, or disorder, and gets treated with another drug. So a simple example of that is a younger child or a child not sleeping by being given a stimulant. And then they're then given a, a blood pressure lowering drug, which is then added to their regimen because they're not sleeping at night. And that kind of puts them to sleep. So there you go. You've got two drugs now that kids on and after a year of that, that kid is that one in 100 or more, that has a psychotic episode because of chronic use of stimulants. And that psychotic episode gets looked at said, Oh my God, that's a manic episode or that. So maybe that child has bipolar disorder. So then you might add on an anticonvulsant. Now that kids on three drugs, so that's an example of what could happen. And it's all halfway to that is it's unclear how, what gets out at first, what comes second, what comes third. What would we what we do know is that a substantial number of kids up to 60% in the general population who are taking psychiatric drugs are on more than one drug.
Nick Jikomes 55:02
So when we think about multiple drugs, so it sounds like if if one drug is being given for symptom A, and the patient has symptom B still lingering drug two can be given to treat symptom B. And if both of them are drugs that can be prescribed, both of them have been shown to be safe in earlier trials on their own, is there simply no requirement that there must also be trials looking for interactive effects and whether or not the drugs can play well together? It sounds like you can just prescribe two different drugs, as long as each one on its own has previously been shown to be safe for its primary indication.
David Cohen 55:39
It's a girdle requirement. In fact, that would defeat the purpose, the very purpose of the randomized control trial, because you try to, you know, you try to limit the number of extraneous variables, if we can call them that way that would impinge on your ability to conclude that, you know, drug A has an effect has a desirable effect that's measurable, and clearly, so you can't contaminated with another drug. That's why only single drugs are tested. In principle, because the problem is with the irony is, in most trials, people are on other drugs, they're withdrawing from other drugs, because they've just been in another trial, let's say, or they're given a drug, often to help them sleep. But that is kind of reported, you know, in the margins, it's not emphasized, in effect, they are being tested for more than one drug. But all the conclusions are about one drug, only the drug have been evaluated for marketing. So it's like, it's confusing. It's ironical. People have it both ways. They say we don't know what goes on, because it's only a single drug when several drugs are prescribed. But because they don't really look at several drugs being prescribed, they can't tell what happens to several drugs being prescribed out there in the community, out there in nature, when the patient is not in a clinical trial. And so everything is kind of confused, and much, much more than you would imagine. It's much more confused than you would imagine. Because that that kind of assumption, you also stated at the beginning, we know the drug is safe when we're marketing it. And that's why we're giving it that's why we're prescribing it. That assumption, again, has to be qualified. If you you know, you ask the the walks into what safety truly means at that time, it's we just need to start giving it for a single indication. So we don't know very much about it. And many people would say we couldn't speak of it as safe. We just say it's safe enough to start using on people in that age window with that hopefully well diagnosed problem who've been monitored now in a trial for six to eight weeks. That's what it say for.
Nick Jikomes 58:11
And, you know, one thing that you said earlier that stuck with me, too, was that the lines have become blurred with respect to the drugs and the reasons we give drugs to adults versus people. So you basically told us that that line is gone, that most of the drugs that we give to adults were also given to children and vice versa? Should we you know, Why has that happened? Is that an area for concern? Or is that reasonable? Because the drugs should be useful for both types of people?
David Cohen 58:44
Well, medicating children with the same drug classes and along the same lines as we are medicating adults. If that's the question, my answer is yes, yes, we shouldn't be because especially because over two thirds of all psychiatric drug use in children is not, quote, unquote, on label it means the FDA has not considered any evidence about the safety and the efficacy of that use in the children is just not, it's done because it's done. It's just a practice. So whereas you could say for adults, you could say that probably, you know, a quarter to a third has not well been tested for adults. But for kids, it's two thirds of that use has not been tested. Most anti-psychotics have just not been tested on children, most anticonvulsants most are useful in children that we know the most drugs are not tested a stimulant and a low, you know, a anti blood pressure drug on children. with ADHD has just not been tested together? No, it's we just do it. But because it's done so widely and we're not getting signals, at least we're not looking actively I would say for signals of harm.
We we keep doing it. Now, you asked earlier about the problems, the long term problems with the SSRIs that had developed over time, because the question could simply be that you could direct me Okay, so what are the real talking about problems? You're talking you saying talk about harms, what are the harms, to detect harm is, is just as complicated as detecting and testing for benefit a billion dollars to bring a drug to market all the clinical trials that have to be done to, you know, to make sure that that drug is not harmful. In fact, well, is is benefiting, it's just so hard, I would flip that around and say, we should invest the same amount of energy to detect signals or harm. Because these things are detectable when you're specifically looking for them. You need hypotheses you need to test for them, you need trials that are very imaginative, and that look at multiple sources of information, you need to look at subjective accounts, you need to look at objective accounts, you need to look at people who know the people, you need to look at a population signals in administrative claims, databases for all kinds of things. That's where you look, and you need to do that over years. And that's very expensive, but we don't do it as systematically, as we search for, quote, for benefits that we're ready to invest in. But we're not. So one of the first harms I would mention are the social harms. And that's what I like to even get into if you want, which is not so much what is happening to your body, although that could be extremely significant. And we still don't know it. But I want to know, but what is happening to society, what is happening to the person's expectations about what they need to do for the rest of their lives, when a problem will arise? What is happening to the culture, what is happening to rebels, what is happening to say young children who are rebels, who used to be rebels, and used to fight against authorities and become painters and artists and creators and change society, what has happened, what is happening to them, when they're told that they have a chemical imbalance or a malfunctioning brain, and they're taking stimulants every day. So that those are the kinds of harms to that, that we might see all around us already. But we're not calling them drug harms, because we're not testing for them, just wanted to own matter of physiological effects. It's also a matter of social and behavioral, and those if and the attitudes that we're promoting in society about how good the drugs can be, and how we're all full of mental illnesses, and how they're all treatable, and how we need to start very early. All of that is creating conditions for how we then perceive and expect the effects of the next drugs to be. So that the social effects in my view are extremely powerful, because they shape what we then, you know, expect, what we anticipate and hope for. So that when whether it's, it's a formerly illicit drug that comes on the market, that we then, you know, whitewash into a this is now really good for you actually, are sorry, we didn't pay so much attention to it. Actually, we were putting people in jail for it, we were persecuting people to see these reversals of value are very profound. And they they play into what we think the drugs are doing, rather than our attitudes about them. And the drugs as kind of living creatures moving through society. And, and, you know, creating change in that whale. So
Nick Jikomes 1:04:14
yeah, I mean, have we have we basically, you know, trained generations of people and started to create a culture where, you know, any, any otherwise normal, but negative aspect of being alive and being human is just medicalized. People just assume, okay, well, I'm feeling sad today, or something's not going the right way in my life, the answer must be that something is wrong inside my body. And I should be on a drug potentially, chronically to prevent this from happening in the future. Have we basically created a culture of people that are just expecting that there are solutions to their problems for for their whole life?
David Cohen 1:04:56
Well, I'm sorry, you you dropped off for a second I thought you had stopped. So my answer to your question is a resounding yes. Yes, we have a created and train generations of people to think that that their distress, their misbehavior, their difficult choices, their oppression, their up all, all the problems of living, you could say, as a human being are probably medical problems that have a medical solution, or, you know, there. And so, yeah, that I that's what we've done. Now. That's the that's the, if you see if you think that so let me put it this way. That's the dominant view today, it's that we are surrounded by mental illnesses, which are, in fact, we say, brain diseases. And so why do we call them mental illnesses? Why do we talk about a new show to its mind and matter? It's this question of how we sort of mix things up a little bit, and call something mental or having to do with mind and something else physical having to do with physical, just as, as it shoots us, we sort of mix things that may not even quite exist as we think they do. And but we have now a, you know, psycho pharmaceutical sort of medical industrial complex, and basically, yes, rests on this idea that these are medical problems, and you need to change your body in some way. And it, it it's done that also by as it promotes a certain kind of drugs, that it's it judges, okay, now, at the same time, it is. It is what's the word it is condemning a another kind of drug. So it promotes and re drugs are usually the same. The drugs that find themselves on the on the blacklist are usually the same kind of drugs as the ones that are on the white, clean, proper, safe, effective, defined prescribed medication, they're usually the same, and they move from one list to the other. They move from one universe to the other. And we don't realize that so now, you know, which you talked about a little bit earlier, which was this notion of like the psychedelics that are coming. And it's, it's the rare observer, that kind of steps back and say, Well, what does it mean that the same authorities that told us that these were terrible drugs, there was absolutely zero responsible use for them, are now suggesting to us that we we we ought to take them probably, and that are telling us maybe the best way to study them is to study them in these clinical trials, you know, we don't kind of wholly scientific water, and then they're going to come out nice and clean, and now everybody can use them. I think that that perspective, itself requires real critical analysis. And we should wonder, what is it just the same old, same old, again, we're told it's something physical, and this particular drug will do it. And it doesn't matter that we were completely inconsistent about the kind of drug that we were really persecuting, not the drug because the drug is just inert. It's just sitting there. You can't persecute a drug, but it's the users of the drugs that were persecuted. So you, it's all tied in? It's hard to, you know, tease out these, the evolution and the changes in the attitudes from the description of the so called probably just being ceremonial and ritualistic and moralistic again. Are we really being scientific?
Nick Jikomes 1:08:59
Yeah, no, it's an interesting point. I mean, with the psychedelics as an emerging tool in treating psychiatric ailments, you know, there's the question of okay, are we just sort of doing the same thing again, that we did when we went from tricyclics to SSRIs? Went from, you know, drug, this one type of drug to the new type that came out at some later point? Are we just going to sort of fall into the same trap again, and just start using these these drugs in the same kind of ways that we've used all these other psychiatric medications in the past? Or is there something different going on here? I mean, one of the things that's very interesting about the psychedelics that distinguishes them from things like SSRIs, when treating depression say is that you give relatively large strongly psychoactive doses and some of these trials in conjunction with psychotherapy, and you only seem to need to do one or two or three doses to get an effect. And so, you know, one of the models emerging there is that in contrast to something like an SSRI, you don't need to be giving daily doses for months or years or decades. You just need one or two or three profound experiences in the right psychotherapeutic context. Is that potentially a key, important qualitative difference here that could make them like a truly novel way to approach psychiatric treatment?
David Cohen 1:10:13
Yes, partly, absolutely, it is something different. It is an outstandingly different way to use the drug. Rather than take it every day for an indefinite period, we'll we'll decide how long you will decide we'll decide. But until further notice, just stay on it, that is completely different from taking a relatively large dose once or twice, in a relatively well defined experience, at least in the clinical trials of psilocybin and others. Yes, that is, and that could lead to some what will be the marketing for that. So I know already that micro dosing of the psychedelics is which has emerged again on its own, not from within the pharmaceutical circles. But that is already a response to that, that is using micro dosing to just sort of kind of keep the person on. So it may not be so financially rewarding to drug manufacturer, to market a drug that will be used just once or twice, or three, four times, or 10 times in the person's life, the whole model now has been to keep people on on the drug for as long as possible for several years, that's been the model. So I'm not, I'm going to sort of abstain from judgment as to what will be the impact of something that will be marketed. If it is marketed that way, as the used ones to vol, you could just imagine that the FDA would give it some very strong kind of would build a kind of a fence, there would be all kinds of regulatory add ons, in terms of this could only be an adjunct with V certain people involved maybe into this kind of environment or something like that, as has been done sometimes with other drugs that presented certain risks or so people, whether it was some of the earlier anti-psychotics And when they came back to the market, they had some blood effects. And then they first marketed with, with the requirement that you had to have a blood test once a week, and that the drug company had to finance that blood test. So that was what it just to give you a sense that it's not just that there are ways that you can limit or restrict the use of the drug in some way. Yeah. When you first put it out there. Oh, it's it'll be marketed. Yeah, that's that that's a that's a great point. That is, you know, the one that I bring up. The other point I bring up is, is whether the the effects that will begin to be reported, now that the drug will seem much more banal, you know, once you standardize it, and you, you control the purity and everything, and you give it a brand name, and you should know it's given to you by prescription, then I'm inclined to believe it will not be experienced the same way. As as, as its previous history suggests it will.
Nick Jikomes 1:13:48
Yeah, that's an interesting point. One of the last things I would love to get your talking about David is, you know, for people who have been taking psych psychiatric, prescription psychiatric medication for some time, especially a long time, what questions What advice would you give them about, you know, what questions should they ask themselves about? Why am I taking this? How am I taking this? Is it really doing what I need it to do? And how should they think about whether or not they should stay on some of these medications? And who they should talk to about that and just how they should introspect about all of those things, as someone who has been taking drugs for in some cases, many years.
David Cohen 1:14:30
Great question. So I'm not going to have a real technical answer to this. It's, it's impossible for me to have that because, because I do look at drugs even in conditions when people report very specific symptoms that are disabling their life and they go see a physician, and the physician gives them that drug and they experience relief, which then reinforces that the whole approach was was correct, that they have this disorder and it was response to physiological imbalance, and, and so forth. And when they slow down or withdraw it, everything becomes worse. So that they, they're going to stay on it. And so the person could be in that situation. The first thing is, it's, if the person in that situation begins to ask those questions that you've asked, Why am I doing this? And and should I be doing this, then it's already it's a positive sign. But the, the basic questions are, that what's happened in the last 50 years, is that the urge that people have to just take drugs and to try them on their own and to, to use them for, for the relief of suffering and to use them to just go to sleep better or to stay awake, so they could cry, and party or whatever it is. That urge, which has not changed much, I think, in 10s, of 1000s of years, and is not likely to change that energy has by modern medicine and psychiatry, and basically psychiatry, as something that shows that you have a deficit? In other words, no, the reason you want drugs is because there's something wrong with your brain, and you need to take the right drug, that it will be based on evidence based methods and will be given to you by an informed expert. And so, I would say that, once you start asking the question, should I take this? And how long should I take this for? You're in for a ride? Because there are many questions, you've got to start asking, which is, what exactly is this disorder? Is it a disorder that I have? Is it a distress is it caused in dodgy honestly, just somehow, it just emerged, like, you know, I just slipped on a banana peel, and I fell, or I just just walked along, and this thing happened to me, or is it
is this in and and situations that are both international, and, and familial. At the same time, they have to do with how you were brought up and the country you live in, and the foods you eat, and the decisions you make, and whether you move your body a lot or you you're online a lot, a whole bunch of things come into what's the matter with me? So I think that that's the next question you're going to have to ask, and you're going to have to ask the question that drugs can be they are a legitimate way of dealing with one suffering, they've always been. And people use them so they can work. And they can live and they can function. But they have a flip side, that people get hooked to them, they get, you know, I don't want to use the word addiction, but they get habituated. And that is another ancient truth about things that helped us and that we like, we just want to be with them. And it's hard to be without them. It's hard physical. Ly it's hard mount to a much more basic level. What is it? That is the matter with you? And if you're using a drug, then why that drug and why that long? So that's, I'm saying open up the questioning, but more technically, I would say you got to use things for the least amount of time possible. As as you hinted earlier, also Nick, you should not use more than one drug. And you should use drugs in their most, I guess I would say natural form, because you use the body's natural defense systems, you know, which is that when you take it through the mouth, it will be metabolized in a quite a different way than inhaling it or take it to intron Bazeley ends of things which make the oral system much more if you will, protective than other ways to take drugs. So I would say that and then look at non drug ways to deal with it. Look at history look at famous people and look at the problems they dealt with, read their biographies and see what they did to deal with the problem. They didn't necessarily focus on the problem they focused on something else. They got much much much busier they threw their whole lives into something else that's why they're great people and we read about them today whether it's Abraham Lincoln or or or Moses, we say boy, these people mister had big problems and look what they did look at the things they did. So I would say look at history and look at How people overcame the issues that that they were plagued with and see whether there's something of that, that that, that you can do
Nick Jikomes 1:20:10
notice is there Dr. Cohn? I think, you know, that's all. That's all good food for thought. And you've given us a lot to chew on here. So I think people enjoy everything you've had to say. And certainly there's a lot of people out there that should be asking themselves these questions. So thank you for your time.
David Cohen 1:20:26
You're very welcome. Thank you for having me.
One, one
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