Psychiatry & Psychotherapy Podcast - Understanding Placebo

Episode Date: November 29, 2018

What is placebo? The original meaning of the word placebo is, "I will please." That statement comes from a time when doctors didn't have our modern code of ethics, and they would prescribe whatever would make the person feel better. They probably had the best intentions, but they also would have known that whatever they were prescribing might not have been a real medication for the symptoms the patient was experiencing. Doctors, even then, knew that suggestion was powerful, sometimes more powerful than the medicine they were prescribing. Laypeople who hear the word "placebo" automatically think of sugar pills. They may think only that it's something a doctor gives to placate and make people feel better when they aren't getting the active medication. Placebos have long been used as a comparison arm for clinical trials. Usually it is in the form of an inert sugar pill or sham-procedure. Researchers can observe a psychobiological response known as the placebo effect. But when thinking about the word "placebo," we must think of the entire effect of it, and it is perhaps better termed "the meaning effect." As I discussed in last week's episode of the podcast, the meaning we give something creates belief, and belief is a potent change mechanism, even when it comes to our physical health. It is especially potent when it comes to mental health. The placebo effect encompasses the therapeutic alliance, expectations, natural healing of the body and mind, and the environment of therapy. It involves the power of suggestion, mood, and the beliefs behind even one positive or negative interaction with a doctor. It also, as we will see, involves studies involving heavy-hitting medication. When there is an increased ritual, there is an increased placebo effect. During a hospital stay, the surgery preparation, meetings with doctors, nurses and therapists can have an incredibly therapeutic effect on a patient. It is possible to see biological mechanisms triggered by psychosocial context and attribute it to a placebo effect. What is the power of suggestion, the meaning effect, placebo effect, and how do we use it or avoid it in our practices and when testing new medical treatments? By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video. Instagram: dr.davidpuder Twitter: @DavidPuder Facebook:DrDavidPuder

Welcome to the Psychiatry and Psychotherapy Podcast, the podcast to help you in your journey towards becoming a wise, empathic, genuine, and connected mental health professional. I'm your host, Dr. David Puter, a psychiatrist who splits his time practicing psychopharmacology, individual and group psychotherapy, medical director of a day treatment program, medical education research, and teaching, residents, and medical students. Before we start, if you're a professional who eventually needs continued medical education, please sign up for the podcast continued medical education yearly membership. For each episode, you can take a short quiz and get Category 1 CME and self-assessment CME.

The podcast receives accreditation through a joint providership with UCI, who is accredited through the ACCME, meaning these CME credits are good for physicians, physician assistants, and nurse practitioners. Further, each episode can apply to the MOC Part 2 self-assessment for family medicine, neurology and psychiatry. Other professions like psychologists and nurses can get health care provider certificates to submit to their credentialing board to receive CEUs. I have a link in the show notes and also at psychiatrypodcast.com. If you have any questions, shoot me an email at DR at psychiatrypodcast.com. Welcome to the podcast. This is your host, David Puder. I'm here with Dr. Mark Ard, a third-year psychiatry resident at Lomalinda University.

And tell me, what is your current and future post in the AMA? Current post is I represent the residents and fellows in California as the delegate from the California Medical Association to the American Medical Association. Future, we'll see. Okay. Future is probably going to happen when we post this. So what's like most likely? I think I'm going to, you know, we set up shop here in California. I plan on staying here.

So I'll be representing California residents and fellows for the foreseeable future. What are some of the biggest issues, and this isn't the episode, but this is kind of like a prelude to the episode here. What are some of the biggest things that you guys are fighting for in terms of psychiatry right now on the state and state level? Psychiatry especially, I think that the big things that we're dealing with is access to kids. affordability of care, but then specifically for mental health, access to, or equal access to mental health. There's the Mental Health Parity Act that I think had good intentions to make sure insurance companies reimburse mental health on par with medical and surgical care,

but the reality of that implementation has been difficult, and you see it in patients that have trouble finding a provider. getting adequate coverage for their mental health needs, getting adequate days of hospitalization. On the inpatient side, which we deal with a lot at Lomelinda is just the bed availability for inpatient psychiatric care. I think that we just don't have the resources available to treat the number of truly sick people that we have in our community, and there's not a lot of funding for it. So that's specifically something that we're fighting for on the mental health side. And I think one thing that legislators don't understand is that if someone's really psychotic or suicidal, they're going to have a bed somewhere.

They're going to be in an ER. Yeah. And an ER is not the best place for these people to be. Yeah. And the law really doesn't spell that out. You know, we have in California the 5150 law, which a lot of states have adopted. but a patient comes in, you know, frankly psychotic and unable to care for themselves. And they're kind of trapped in a system where they're in the emergency room.

We're not going to let them out of the emergency room. There's no place for them to go. And then we don't have a legal system that spells out what to do at the end of those 72 hours. And patients are not receiving the care that they need. We have a pretty robust consultation service at Loma Linda, and that still is a far cry from an inpatient hospital. hospital that has the clinical staff available to help them. And there's just, you're right, they just get boarded in the emergency room and kind of crowd out space for other patients as well.

Yeah. So that's a little bit about Mark. The other piece of Mark that I've really enjoyed throughout the years is Mark has taught me how to do starting strength, some strength training. And so how did you get into strength training? I played football in high school. I think strength was always a big part of who I am and what I enjoyed doing. But I kind of mostly just messed around until medical school. I got a really bad back injury. Had to have two surgeries, I think in 2012. I had two disc surgeries.

Kind of stepped back and said, you know, is this the end for me? I remember having a thought, like, I'm never going to lift weights again. Like, I'm going to use bands. And, you know, I wouldn't be allowed to, like, lift things over 10 pounds forever. I don't know where that idea came from, but that was the fear. No, I have patients that have had back surgery, and they say, I can't lift anything more than 20 pounds. Ever. And I can't, my doctor has told me not to squat.

Yeah. I remember driving home from the surgery and fearing sneezing. That was like, somebody had said, like, you can rewpture a disc if you sneeze too hard. And I thought, oh, like, I can't even sneeze. How am I going to hold my children? And I found starting strength, I found weightlifting in general. And I was like, you know what? We're going to take it slow and progress.

made a lot of progress in weightlifting and, you know, in most things that I love and enjoy, I can't keep that to myself. And, you know, I've shared that with any and everybody. And you have a good, you know, sports background as well, too. So it took to it like a fish and water. And I would say, when you say it worked well for you, it decreased your pain, right? There's a few things. Maybe more functional. Yeah. So it made me more functional. I'm able to, you know, lift more now than I ever had. I, wish I had known this back in high school. I would have been a better football player.

But the functional part of it, I think, is big, too. I mean, back injuries don't necessarily happen underneath the bar. They happen when you're putting a 20-pound baby into a car seat. And so being stronger overall means lifting a 20-pound baby is that much less of my max. And I can just do things now that I wasn't able to do even just a few years ago. But more importantly, the lack of fear, I think, around injuries. I've tweaked my back still weightlifting. I've gotten injuries.

I've gotten sore. And just knowing that I can get back to it and train and heal has been really empowering. And I think spreading that to other people is like, look, you're going to get injured. Life is going to injure you. The weights might injure you sometimes. But you can recover from it and there's a path through it. I think it's been really helpful. Yeah.

And so I'll definitely have Mark on in the future to talk about things going on politically, current events. in psychiatry as well as strength training. But today, we have thought that our first topic that we could do together would be on placebo. Yeah. So, Mark, define what people when they think of placebo. What do they think? Ooh, that's a good question. So people who aren't reading scientific studies.

Yeah, I think when people think of placebo, think of a sugar pill, right? That's like the common thought about it and that it's something that a doctor gives you that makes you happy or gets you out of their office or something that's prescribed to placate and make you feel better when in fact, you know, you're not really getting the active medication. You're just getting something fake. Right. And so what would be maybe a common understanding of placebo, but, not the correct understanding of placebo. Like, if you hadn't really thought through and you heard, oh, placebo's worked 30% of the time to treat depression,

what do you, what do most people do you think, think that that means when they hear that? Yeah. So there's the effect of the actual medication, and then a lot of our studies are done with randomized control trials where we compare an active medication with a placebo. And when people look at those studies and they see, you know,

a 30% response for placebo and then a 50% response for a medication. They say, oh, the sugar pill somehow gave a 30% response. Like somehow this medication or this pill that has, you know, nothing but that doesn't have the drug in it, it just has, you know, an inert substance somehow got that 30%. I think that's the most common misunderstanding in physicians and scientific people. Okay. Yeah. So then we come to kind of like, okay, what is it more nuanced?

view of what a placebo response is caused by. Yeah, and I think that that's a better word to use the placebo response, because that encompasses kind of everything, right? That encompasses the pill itself and whatever effect that does have, but also the meaning behind it. Sometimes I've heard it described as the meaning effect, not the placebo effect. I like that. Yeah, yeah.

Because actually the week before this one comes out is an episode on meaning. Yeah, I mean, meaning is everything. And it's the same with medication. So when you think of the placebo effect, you're talking about the doctor-patient relationship, right? You're talking about the therapeutic alliance between the patient and the provider. You're talking about the environment. You're talking about the expectations that the patient has for what this medication or placebo is going to do. all of that gets encompassed in the placebo effect.

And then there's things, even outside of that, there's regression to the mean, which basically means that sometimes you're going to measure things high, sometimes you're going to measure things low. And in general, when you have abnormally high measurements measured one time, the next time you're more likely to have a normal measurement, and all of a sudden it looks like you're having an improvement. movement. You also get the, along with regression to the mean, you get the natural course of the illness. I think that's one that people forget. Natural. Yeah. That's the one that when I was reading

about this, I was like, oh yeah. You kind of forget about that, right? So there's some people that are just naturally going to get better. Yeah. And, you know, outside of mental health, like, one of the most common places, I see placebo effect. I mean, you see it whenever you go to Walgreens or CVS, is all these medications for like the common cold, right? They're all placebos in a sense. There's not real evidence for high-dose vitamins, having a big effect on the course of the common cold. And yet when do people take it?

They start taking, you know, like airborne or these medications like day five, six of the common cold because they're like, man, this is driving me crazy. They start taking it all of a sudden they get better. They say, oh, it must be this thing that I took. When in reality, that's the natural course of a common cold. It gets better on day seven. So you start taking this medication right near the end of it, and then you get better. And you think that this thing had an effect.

I can see someone in the audience saying, wait, Margar, are you telling me that high-dose vitamins don't work? But what if you inject them? Those really, really work, Markard. Yeah. And that's the thing. I think a good place to have this discussion is what we're trying to do in evidence-based practice, is what we're trying to do in treating people

because, you know, I think the long course of helping people is a story of people trying their best and people trying to care for those that they want to get better and yet not really knowing what we're doing and not having a system for seeing if what we're doing is actually having an effect. So when we look at scientific studies, what we're really trying to tease out is,

is this thing that I think working actually working and what can I compare it to that I don't think has the same mechanism, is a placebo in a sense, to see if there is a difference, to see if the thing really works. Because the reality is we have a lot of good ideas for things at work that really just don't work. And, you know, the evidence for high-dose vitamins isn't there. The evidence for, you know, pick most of your herbal supplements.

It just isn't there. You're offending people right now, Mark. I go right to it. Yeah. And I would say also, like, procedures have a higher placebo effect than just taking a sugar pill. So, like, injecting something with someone gives a higher placebo effect than just taking something by mouth. Yeah. And any, I would say the increased ritual, whenever you have an increased ritual around something,

that will increase the placebo effect. Yeah. And that goes back to mesmer to some of the early sort of, you know, he would take people and he had this whole ritual and how to cure these people. And he would cure people, I think, with conversion disorder through very, very strong suggestion. And, you know, people really bought into this. Yeah. Yeah.

Some people. And you're right, the more outlandish or the more hands-on the intervention, the more likely it is to have strong effect. We deal with that in psychiatry. You know, we look at one of our gold standard treatments, electroconvulsive therapy. And there are studies that compare it to sham treatment, which in, you know, surgery or intervention is what we call kind of the placebo. It's getting everything set up except for doing the thing that we think is actually doing the change. So when you think of ECT and sending electricity through the brain to stimulate a seizure, we think that that's what is having the effect.

We say, okay, well, let's set everything up and just not do it. So we put the patient asleep and then they wake up, but they went through all of this rigamarole, right? They got dressed up. They came into the clinic. They got onto a hospital bed. They talked to nurses and staff members, the anesthesiologist, the psychiatrist, and then they fell asleep and then they woke back up.

That right there has a huge. effect. And yet ECT has a little bit more of an effect on top of that. And that difference is what we think of the therapeutic effect of everything else that goes into it, you know, the whole environment and the attitude of ECT. That's the placebo part. Right. And if you're listening to this, and this is disorienting to you, the point of studying this

and of understanding it is there's a couple points. One of them is to be able to read studies critically and to be able to read them with an eye for placebo, okay? Because when we read studies, we want to look at them and we want to say, what are we controlling the treatment group two? And are there parts of the treatment that we're not controlling for by the placebo? Right.

So for example, a lot of strength training, which I've read a lot of these articles, the effect size is much higher than antidepressants. The effect size is the effectiveness of it compared to the placebo. But the placebo is doing nothing. Right. And so when you do nothing, you're not meeting in a group of people. You're not having a coach in a group of people that you're doing exercise with. and that sort of community is not sort of separated from the effectiveness of the exercise.

Right. So you could be critical of, well, how much is it just meeting with a group of people? And so you have to design studies with that in mind. And there are good studies for strength training where they look at that kind of thing. So I think that's one important reason to study and to understand how placebo influences something. And I think it starts with identifying what you think is actually making the change and really naming it and putting the boundaries around, you know, this is the thing that I think has the effect. Okay, so how can I simulate everything up until that point? You deal with the same placebo issues in therapy, right?

It's kind of hard to have a sham therapy. You know, you imagine a trained psychotherapist that has a model for doing therapy, whether it's, you know, cognitive behavioral. therapy or psychodynamic therapy or whatnot. And that's their model that they go in. Well, how could you, what would be the sham intervention, you know, just, you know, letting some some college student just try their best. But what we use for most studies for psychotherapy is waiting lists as the placebo. It's the ones that didn't get into treating, talking to a therapist. Well, of course, like they're not going to have anywhere near the improvement as somebody going to their therapist because there's not only the therapeutic intervention and the different techniques used, but there's also the office,

the environment, the smiles of the staff members, you know, the warm smell of cookies, if that's how you set up your office. I mean, all of these things affect the outcome, irrespective of the actual intervention done. For medications, you know, you look at medications versus concebos. I want to say something about the therapist effect. And I think, first of all, I agree with everything you said, but I might add, I think that's why I'm very interested when they look at in-between therapist effectiveness and what is going on differently from the most successful versus the least successful therapists. Those are the studies that are very, very interesting to me. And specifically, like, that's where, like, the therapeutic alliance shows up, like, the people

who are rated as having a higher therapeutic alliance, their patients have better outcome. and the people who have higher empathy in a series of studies have better outcomes. And the people with higher interpersonal skills have better outcomes. And so to some degree when I'm thinking about beyond the model of therapy, right? Because I think that there is some importance of the model of therapy for a given patient population. Like there's some patients that are just going to respond better to certain types of therapy. But beyond that, it's okay, how does this therapist connect with the patients? And as a psychiatrist, how can I facilitate that occurring even better as a, you know,

the medical director of a program where I'm overseeing and seeing patients as they go through therapy really intensely? So those are things I think about. Okay, go on to the next one, medications. Well, and so, Ray, I think all of that that matters. And you see it not only in mental health. I remember being a medical student and rotating with a surgeon who, you know, he was telling me all the things he does in his outpatient practice, like in between doing the surgeries,

he's telling me all the things he does to make the patient feel better. And in a sense, this is part of that placebo effect, right? Like, you know, even though his visits were like, you know, five to ten minutes max, he always made sure to sit down, right? He always put a hand on the patient, even if it was just on his shoulder. or your patients really respond to that. These are all things that you're adding to the experience beyond the actual medical intervention you're doing.

But when we talk about medication, so you think about an antidepressant and you're trying to get FDA approval for prescribing this antidepressant, you have to prove its efficacy. So you have to put it up against placebos. But one of the things that most of these studies don't do is they don't put it up against the waiting list. So really there's two types of inactive arms of these studies. There's getting the inert pill, the sugar pill, and everything that goes with you thinking that that is the real medication.

But then there's this group of people that never made it into the study. There's this group of people that are depressed and they didn't get any intervention at all. If you track those three groups, basically the waiting list group, the placebo group, and the intervention group, what you see is, you know, like, 30% of the people in the waiting list group get better. But then above that, there's a percentage of people that get better on the placebo. And your hope when you're making this drug is like, is there a group above that that gets better? And yet we call the effect size of comparison to placebo.

I mean, this is where I would say you have to read the study carefully. Right. Because they'll use effect size to compare it to, the wait list group in some studies. Right, and they have big numbers. And they have big numbers. And in other studies, they'll compare it to an active placebo. Right.

So on the trajectory of it, so you have the wait list, and these people are the people who are spontaneously getting better. Right. It's the natural course of the illness, right? So if you have more severe disease, less people in this group are going to get better. Right. And if you have more severe disease, actually like the effectiveness of antidepressants goes up.

So the higher the Ham D score, if the Ham D score is really, really high, then the effect size is the highest for the active medication. That's what I've seen. If you have a randomized control trial, and instead of doing 50% of the people on the active medication, you do 75% of the people on the active medication. Have you read what happens there?

So the efficacy of the placebo goes up. Why? And the wild thing about placebo is it's all about expectation and meaning. And if you start from expectation and meaning, you can almost guess how all of these crazy scenarios go. So in the case that you made, there's one study design where half the people get placebo and half the people get the medication.

But instead, if you give three quarters of the people the medication and only a quarter of the people, the placebo, then more people, and of course when you get their consent to do this, you have to tell them that their chances of getting the medication is 75%. They think they're going to get the medication. So their response goes up even if they get the placebo. Not only does the placebo response go up in that group, but the effectiveness of the medication goes up as well.

And again, it's expectation, it's meaning. They think they're getting the active drug, so the response goes up. And vice versa happens, right? If you have a two-to-one placebo to intervention, I don't know why you just design a study like this, but you gave more people the placebo, their response is going to go down because they think they're getting the placebo. Yeah. Well, and then, you know, we're talking to us. other mental health professionals and aspiring mental health professionals.

And you could talk about the mechanism here. I kind of break it down into three different mechanisms for the placebo effect. One of them, we don't deal with as much in mental health, but it's probably the most common one. So the first one being like the opioid system, and that's where a lot of the evidence for the placebo effect comes from, pain relievers. And, I mean, it's just wild what some of these studies show, you know, You have more of an effect if you know you're getting the medication versus if it's kind of snuck in in an IV. You already mentioned if you get a shot, it has more of an effect than if it's a pill.

And the thought is that the opioid system in the brain is basically telling you that you're getting a pain reliever and therefore I'm going to relieve the pain. The other pathway that we deal with a lot in psychiatry is the dopamine pathway. and really that's built around expectations. There's studies showing that the brain lights up to a placebo just almost as well as it does an active intervention because the brain is expecting to get the active intervention. So it starts responding that way anyways. One important study there is on Parkinson's. And so Parkinson's disease is a dopamine deficiency.

And what they found is that with a placebo, the people with Parkinson's actually had, increased dopamine. Right. With both the placebo and the active medication. Well, and with Parkinson's such a great model because it's, you're right, it's directly a lack of dopamine. So I remember reading studies where they would give people an injection of medications that help with Parkinson disease and help with the movement disorder part of it.

And they randomized them to two groups and they told one group, you're getting, a really expensive shot of medication, another group that you're getting a discounted shot of medication. Both groups are placebo's. And yet the group that gets the expensive one has a better response than the group that gets the cheap one. Again, because you have this expectation that the more expensive medication must be more effective and your brain primes you for it and then it acts along this dopamine pathway to increase your response, whether it's real or placebo. And therefore, you respond appropriately. And in the case of Parkinson's, and in the case of Parkinson's, since your movement disorder gets better.

Yeah, not only does the cost of medicine, but the, I think the color of medicine. The color of the medicine, yeah. The color of medicine changes the experience of the placebo. The brand name. So there's kind of expanding both of these, the dopamine and the opioid pathway. There's evidence that brand name aspirin.

So they took four groups, right? They looked at brand name aspirin, generic aspirin, placebo brand name aspirin and placebo generic aspirin. And it went right down the line. If you got brand name aspirin, you had good pain relief. If you had generic aspirin, you had okay pain relief. But if you had brand name placebo, you had a better pain relief than if you got generic placebo. Again, it's just what you think is going to happen with it.

If you like certain colors or shapes, you're going to have a better response to colors and shapes of medications. The other one, I'll mention the other pathway too that I think is really important, the kind of like frontal lobe pathway, right? The executive pathway. And this has been shown to be helpful in anxiety disorders. You give an anti-anxiety medication and, you know, the frontal lobe mediates that response. And placebo or medication, people have an anti-anxiety response to you giving them something you tell them will help with their anxiety. Absolutely. And this is what we deal with in practice too,

is some element of both the actual intervention, the medication that we're prescribing, but also the expectation of how people are going to respond to it is I think just as important when we prescribe. And to that, just a sort of cross-corollary with that, is if you talk to alcoholics about the moment they decided to relapse, okay? Not when they had the beer,

or drink. But the moment they made the decision to have the beer, that is the moment that their anxiety went down. Right. That is the moment that like the calm of the storm, right?

And a lot of times what preceded that was a feeling of being out of control and like chaos. And so it's like the decision to drink takes that away instantaneously. Yeah, and I mean, I think a sense of control would fit into that category of, you know, things that we call the placebo effect, a sense of control. And, you know, in the case of an alcoholic relapsing, as bad as that is, them feeling like they have some power over themselves and can go back to something that they know and has given them relief in the past.

I mean, that mediates a lot of temporary relief. Yeah, and feeling control, when you're feeling incredibly out of control is very dopamine surging. It's a move in the right direction physiologically to feel in control. It can really stabilize someone psychologically. So, I mean, I think the interesting thing about all this, I mean, I love to read the studies on these interventions and the sham interventions and the study designs and really pick it apart to poke holes in all these studies. But I think the interesting thing is like, what do you do with that? What do you do with that in practice? How do you take your knowledge of the placebo effect and really

all the things that go into it, all the biopsychosocial aspects, how do you translate that into to being a good doctor and how you prescribe medications and how you counsel patients on what to expect, both good and bad about medications, because there's a host of literature on this. And I think it shows that the conversation that we have with patients is very important in their eventual outcomes. So one thing that you may not know about Mark Ard, but he also did a master's in ethics. So tell me, Mark, what is it an ethical way? of thinking about this. You know, if only we weren't so driven by our ethics,

we would have such cool studies. It would be terrible. You better, like, you better give the subtitles to what that statement means. Yeah, I mean, again, like, we, the placebo, right? Placebo, like the word placebo means, I will please. And really what this was is, like, before we had good interventions, doctors would just prescribe things to make people feel better. And I think with the best intentions, but they also knew that the thing they were prescribing

didn't actually solve the problem. If somebody has intractable pain from cancer, if we don't have something strong enough, I'll prescribe you something and tell you that it's strong enough. This is how, like, medicine used to be. And now, you know, with respect to patient's autonomy, we don't do that. You know, we let them know if they're going to be in a placebo group. We don't prescribe with the intention of giving them something inert or giving them something useless so that they don't come back so that they feel some relief that you know is the placebo effect.

But yeah, I think that we've changed a lot in how we think about the placebo. And the reality is we probably do prescribe a lot of things that most of the effect is driven by the placebo effect, not necessarily the medication itself. I would say it depends on the severity, right? Because as the mental health diseases get worse, we know that the effect size increases. And I would also say that, you know, like if you look at studies like Katie's study,

a lot of it is just not following up. You know, like, what is it, like 70% of the patients like had non-compliance issues. So there's more than just the placebo complications for why a successful treatment isn't occurring all the time. But that being said, we are well aware that there's a number of patients that we will treat that will get spontaneously better that will respond to a medication or a placebo. I think one of the things that I think about when I'm seeing patients is I'm not just prescribing a medication. I am always doing psychotherapy to some degree. And a lot of the times I'm not even talking about medications with patients.

I'm talking about their life, what's going on, their stressors, even when I'm doing medication management. And I'm doing that because I think that the value. of the therapeutic alliance will give better outcomes. I think connection in and of itself is what it means to be human and it's enjoyable. And so there's an innate pleasure that will come both for me and from the patient when that occurs. And it will change the outcomes beyond the medications. Because I think that's one of the main sort of aspects of the placebo is the therapeutic alliance. Right. And I think, you know, I mean it in good faith. Like we prescribe things because we honestly think that they will work and, you know, the medications that we choose, you know, we hope that there's evidence behind them for the reason that we're prescribing them. If we're giving a medication for anxiety, you know, we're telling the patient that this is for your anxiety. The reality is I don't know if this medication that I'm giving you, if the effect, your anti-anxiety effect,

comes from the actual medication itself, something about the medication working on the chemicals in your brain, or if it comes from everything that you just mentioned, the interaction with the patient. But I'm doing it in good faith. I really do think that it will. And the evidence at least backs me up on this and my personal experience, the experience of those that I consult with. But you're right, like everything else goes into it too. And I think that that stuff is just as important, you know, whether or not the dose that you're giving or the medication you're giving actually Um, you know, has that beneficial effect or honestly anything would have had a good effect on them if you gave it with the, the, the council that you just mentioned and the care and empathy and connection. Um, because all that has, has a huge effect, um, you know, separate from the medication itself.

I also think sometimes we don't know if the medication is going to work. And I think this is why as an outpatient psychiatrist, I like to start one medication at a time. And to mindfully think about how and when the changes occur and what are the differences. And who sees the differences? Does the patient see the differences? or does the patient's spouse say, whoa, something happened and don't change a thing? Right. You know?

I mean, this is a question that I have in practice a lot, and I don't know if, you know, the evidence in literature is very clear on this. You know, if a patient has a response to a medication you prescribe, what do you do with that knowledge? I think one, a common medication we prescribe, something like Prazosin for nightmares. You know, I tell them this is for your nightmares. I expect your nightmares to go down and taking this medication. In the back of my head, I know that there's studies that show improvement in nightmares in large groups of patients. And that improvement is better than the placebo that was given in those studies.

And yet, even for Presden, there's controversy of whether that's true or not, because there's lots of studies that some of them tend to contradict each other. But at the end of the day, I think prescribing prescison is going to help your nightmares. And so I give you the starting dose, one milligram. And yet the evidence is for higher doses. All of these studies are five plus milligrams. I give you one milligram. You come to me next visit and say, Doc, I haven't had a nightmare since. Is it the one milligram?

Is it something about that medication that's getting rid of the nightmares? Or is it the priming of our conversation? Is it the expectation that taking this medication is going to improve your mind? nightmares. It doesn't even matter. Should that change what I do next? Should I say, yeah, I know you're on one milligram, but let's keep going up because the evidence shows, you know, it works at higher doses. I wouldn't do that in the outpatient study and I keep an eye on it and keep them at one milligram. Well, you wouldn't do that for a number of reasons. One is because you don't know how they're metabolizing that medication. You know, some people are going to metabolize medications and it's

going to be a higher dose than other people. Right. So there would be other reasons not to go up just but you know like don't mess of success that's one of my sort of lines of like okay once you have something that works like why change it yeah yeah okay maybe because you're trying to reduce some side effect um and that kind of goes into a different topic of do you tell people the side effects or how do you talk about the side effects in a way to not cause a belief oriented side effect Well, and you know, talk about ethics, right? Like, what do you put into the informed consent process for patients? And that's a difficult answer.

I think, you know, some of the standards we use are circular. It's like what a, the reasonable disclosure of another professional would be. Okay, well, you know, then I'm setting my standard on everybody else's practice, and they're doing the same, and it's kind of regressive there. For some places, I believe the British system, the legal system, the standard is the patient side, what a reasonable patient would expect. And that's a little bit of nuance between what the disclosure would actually be. But in reality, you're right, like all these medications, you watch an ad for a medication. They list like 50 different side effects with headache, nausea, dizziness, upset stomach, diarrhea, and constipation, you know, chest pain, arm pain, numbness, tingling.

I mean, 90 different things that you could have. and it's also associated with death, but we don't know why, so we give it a black box warning. Do you say all that stuff? I've heard some suggestions, which I've started to do, and I think makes sense. I just have a printout for common medications that I prescribe, and it's everything that is above 1% in the studies, and then also the deadly side effects or big dangerous side effects. So it has a list of these common side effects and also, even though they're very rare, the ones that would need medical emergencies. And it's like a sheet and I give them and I say this is what you could expect.

And yet just by doing that, just by listing all these things, they're more likely to have all of those side effects. Right. And what happens if you have like someone who's a hypochondriac who like their fear of having these things will then prevent them from taking a medication, which could otherwise be very, you know, life-giving. Right. Well, and the solution is the stuff that you just mentioned, right? So we actually share a patient who has, he, you know, he's a young guy and he has a lot of fear of medications.

He took an antidepressant in the past, and he was more suicidal during that time. He will tell you that it's the medication. I honestly don't know, and I tend to not speak in that terms. I don't like to connect things, even if, right when I started the medication, you became more suicidal. I don't know if that's the medication doing it or the opposite of the placebo, this nocebo effect. But anyways, he fears medication. And yet, you know, we see him get sick and we see him struggle, very anxious and a lot of obsessive thoughts. And despite, you know, our attempt with therapy, there's this thought in the back of your head that like, man, medication would

really help this kid. And like, how do you convince him to take it when he carries all this trauma around it. And the reality is the first time we talked with him, there was no chance he was going to take a medication. And then multiple visits into it when he's built that therapeutic alliance and trust and belief that what we're saying works. And he's seen it work in therapy, like being able to use some of the techniques that we've given to him. He's like, okay, I think they're on to something here. And also they keep suggesting a medication. I think I'll try it. And, you know, it's huge to see him, you know, reluctantly, but, you know, choose to give it another try and put a lot of faith into us. And I hope for the best with it.

But I'm also expecting for him a lot more side effects and a lot tougher road as far as response to the medication. Yeah. And if he comes back and he has side effects and he has concerns, then we'll say, you know, I'm really glad. you told us and those are things that we take seriously and we listen to them and we try to make sense of them in our own minds are these things we should worry about are these things we should push through um and i think also part of the practice of psychiatry is once you treat you know several hundred people on a certain medication it's like you kind of have an expectation of what are the side effects that concern you and what are the side effects that don't concern you um and so the things

that I highlight for patients, usually when I'm talking about side effects, are the side effects that concern me that I want to be called about. And I also want them to call me if they're thinking about stopping the medication for any reason. Because if they're thinking about stopping it, usually there's some sort of side effect that's bothering them enough that they want to stop it. And usually for good reason. And so I would like to have that conversation with the patient and they have ways of getting a hold of me. And I think that that is valuable in and of itself. If there is some issue that comes up, you can reach out to me and talk with me.

That right there is a placebo effect. In a sense, like what we're talking about, though, the fact that you make yourself available and you have this connection with them that they can trust you, they're less likely to have an adverse. effect and they're more likely to have a better response to the medication because you're there for them, that that bond means something in outcomes. Well, I mean, and the bond means something because they're not just coming in and talking about the medication.

Right. People come in and talk about their sexual dysfunction. They talk about their trauma. They talk about, you know, the biggest, most stressful things. that they've ever experienced in life. And I think it helps, like, when I have heard, you know, many, many stories, and it's like it doesn't cause the same level of fear in me that it might cause someone else if they were to tell the story to.

It doesn't cause dissociation in me. Like, it probably would cause in someone else. And it doesn't cause anger or judgment in me. like it may in someone else because I may have a way of understanding it and making sense of it that other people don't have. So when those moments happen, you know, that's therapy. That's change is occurring. And I would say you could make an argument that part of that is placebo,

but then I would say our definition of placebo needs to be a little bit more nuanced to the whole aspect of the treatment of the treatment. treatment that's not the act of treatment. Right. The meaning response. The meaning response. Right. And the meaning response extends to, uh, the effectiveness of your ability to connect with clients and build a therapeutic alliance and walk with them through tough things that they've gone through. And some of that's just being a normal person who, uh, has good boundaries and is professional and has, and that in and of itself, I think has value. Um, and, and I think

that's not something everybody either does naturally or even strives to do better. I mean, I think that this is one of the joys of working in mental health is that this is something that's on our mind. We do think about doing this for patients' thinking in this sense. But, I mean, really, this would work in every specialty and other professions. Somebody comes in and they're saying, you know, having the side effect of a medication, well, you're like, okay, that's kind of a common side effect.

So what do you say to them? it goes so far to empathize with their distress, right? To notice that they are fearful, upset, in pain, and for you to say, man, that seems like it would be really difficult. I'm sorry that you're going through this. And also normalizing it and saying this is something that a lot of people do deal with. And maybe we talked about this or not. But just that both sides of it is not overreacting, like you said,

not dissociating, not freaking out when they're having a side effect because it's something you've dealt with and you've seen. So they have some assurance and the look on your face is assuring right there because you have this authority and experience with this and they feel relief there, but also the connection with them makes them feel like they're heard and understood and you're going to help them through it. That right there has a big meaning effect and it potentialates the next treatment you're going to do and the fix you're going to make and builds that trust there. Anybody can do that. A cardiologist, a family doctor, a surgeon. That's just something that we try to focus on in mental health. Yeah. And I think also this sort of comes into where I think

sometimes as psychiatrists, we need to stop and consider other modalities of treatment and not just psychopharmacologic treatments. So with patients, I'm thinking about, you know, do this. they have obstructive sleep apnea? Are they exercising? What's their diet like? What's their connection with their family like? What's their connection with their friends like? What's their connection with their spirituality like?

What is there, you know, all these different facets of what it means to be a human. And not just reducing things to like the only way is to take this medication. That's the only thing that's going to help you. You have a serotonin deficiency. And so you need an SSRI to increase your serotonin. You're not just a bag of chemicals. Which is, by the way, the effectiveness of psychiatric medications and placebos has gone up over time. Right.

And one of the arguments for that is the pervasiveness of very simple models for why depression takes place. Right. Depression is a serotonin deficiency, which, by the way, that's not true. Like most of medicine, it's nuanced. Right. It's very complex. Like depression is, I'll do an episode in the future on what causes depression. And it'll be, you know, a bunch of stuff.

It'll be like 10, 20 different theories. Some with different amounts of evidence that's persuasive and different amounts of treatment that are persuasive on what causes depression. So it's so complex that it would take, you know, digging into it for several weeks from someone who's trained in it to present it in a way that's meaningful. So it's going to be very, very hard to relay that. And in the complexity of it, it might actually make the placebo response go down.

So that's where like very, very simple solutions actually are more believable. Right. Well, I mean, this kind of, you know, segues into another issue that we deal with is just convincing people to take a medication because you're trying to balance this complex clinical knowledge you have. I mean, you know, you can give hours and hours and write whole books on different theories about depression.

And yet, in a 15-minute visit, you know, what do you say to somebody to convince them that they should take it? And I think that it depends on the person. And that's, I think, what makes a lot of this exciting and fun. And the reason why I think we went into medicine in the first place is to really connect with people to help them. Because the reality is the evidence for these medications, as good or bad as it is, doesn't show a lot of difference between medications within a class. So you have somebody come in for depression and, you know, we have some studies, you know, showing this medication works, that medication works, you know, to use placebo, I mean,

placebo, Prozac or Zoloft or Lexopro. Well, the evidence is, like, they all work and only to a certain extent. So like, how do you convince somebody to take it? And then the conversation starts. And there's a lot of different ways you could take that. Yeah. I mean, I had a patient today who was concerned because we switched from Lexapro to Simbalta. And her concern was that she took Lexapro 10 and she was going to start on Symbolta 30.

And it was a big number change, which scared her because I think the exact phrase was, is it to be too powerful for my brain. And like, how do you, you know, convince somebody that this change is further in their best interest? And a lot of her symptoms made more sense to switch and her lack of response to a few different antidepressants. I mean, the algorithm was there to make the switch. And yet, her big concern was the number. And I get that. I get, you know, the pill size and all this type of stuff. People are trying to attach meaning to things. They're trying to understand how this works. And it's very complex. It's very,

It's very complex. And so with someone like that, you know, you would say, oh, thank you so much for, you know, wow. I hear you're concerned about that. You know, let me just give you a little bit of education on the dose range of these different medications. You know, Lexa Pro, we usually start at around five. Max dose is around 20. Sometimes we go higher, but usually it's around 20. For Simbalta, you know, usually we starting doses around 30.

max dose is around 120. So. And that's the conversation you have to have. And then the meaning, you mentioned meaning, like, how do you ascribe meaning to the reasons you're doing treatment? And everybody's, I remember one of our professors, you know, broke people down by their Myers-Briggs type. And that's just how he approached people. And you got to put people in some sort of system for you to even begin to interact with them. you know you talk to me if you want to convince me to take a medication to show me the evidence

make a good convincing argument you know you want to convince my wife to take a medication you know tell her that it's for the kids and it's different how we respond to the incentives to do treatment and and I think that that's part of the conversation part of the joy of mental health and I would I would say to that like of course in our like sort of intuitiveness we may decide what we will say to one person and say to a different person, I would say we should, I would never not tell the truth. Right. So if, if I thought that this person's depression was severe enough to cause issues with how they raise their children, it's because I've read, you know, edronic and his studies, the still face experiment with depressed mothers. And that's the evidence that

I would be drawing out, maybe more in a narrative way, in a way that could be understood by her. I mean, for me, just cite Star D. For you, I would take you through, I would take you through the data on, you know, and like, yeah, we'd have a, we would have a debate. You would want a good debate. You would present all the counter arguments, and I would continue to firmly argue my position, or I would change my position. or I would change my position. And I've done that a couple times and you've done that a couple times.

So I think there's some people who need a good argument and a good polemic and there's other people that need a story and a reason and a parable of sorts. So, yeah, where do you want to go from here? Well, I mean, I think that this all comes back around to the placebo effect, right? This is what we started with.

But really we're talking about the meaning effect and we're getting away from, you know, the sugar pill and what that means. Really, there's an effect outside of the medication itself that is, you know, at least as meaningful. And it encompasses all the stuff that we focus on here, the setting and the context and the story. And ultimately, I think the thing to take away is for you to be effective. And there's really good evidence for this, too, right? There's evidence that if you are more warm, empathetic, caring, you listen to what the patient says. You're not typing on a computer.

All the time. Yeah. I mean, even just how the computer is set up in the room, your staff is more warm and inviting. You're thinking about all of this stuff because not only do you want to prescribe the right medication, you want to treat the patient. You want them to get better. And you think about all of the stuff that goes into the quote unquote placebo effect. and you think about them consciously and apply them diligently,

you can create great outcomes for people because you care about all this other stuff as well. And also you decrease the likelihood that they stop taking a medication, that they have bad side effects. You get all of this benefit by focusing on this stuff. Ultimately, that's what I want people to take away. Yeah, ultimately, along similar lines,

I would say, you know, we spend a lot of time in medical school and in residency, focusing on the medications, the side effects, the, you know, all of the studies, the details, the psychopharmacology. And I see that in medical education at large, there is a loss of the interest of the science and the humanity of connection

and the therapeutic alliance. And how do we connect with the people that we're with? And seeing that as part of our, our sort of role and expertise, you know, is that we can continue to learn and we can continue to grow and our ability to connect with people. And, you know, part of that's being open to feedback and part of that's continuing to listen to a podcast like this where we talk about it. And part of that's, you know, reading books or articles or, you know, I don't know, videotaping yourself even like we do in residency here and watching yourself interact with people so that you

don't just believe something that isn't true about yourself and how you interact. And part of that is, you know, valuing it as important as the psychopharmacology and seeing it as part of what is going to always be, you know, pivotal in mental health. Because mental health is not just a disease of, you know, gout, which, you know, you could argue that gout is increased by stress as well, I guess. But mental health is, it's, it's part of our like, our human experience. Right. Yeah, I mean, there's an existential side to it too, right?

And that's what we're ministering to. And I think the thing to add to what you just said too is have a community of people that you challenge and engage on these topics with. I think, you know, the private practice world can get lonely. The solo practitioner world can get lonely. The hierarchical nature means you don't get a lot of people questioning what you're doing. Having colleagues and mentors both above and below and where they are in life and experience. It goes a long way and you can look to people for guidance and also give guidance to others

and to challenge you along the way. I think that you'll add to the meaning effect that you're having on people. Perfect. Well, thank you, Mark Ard, for coming on. Glad to be here. Mark Ard is a close friend of mine, so I imagine I'll have them back in the future. If you have any questions, I'll put up my social media profiles, a link to the website, and places you can post comments. You're always free to jump on the website and shoot me a question through the forms or your thoughts. I get a couple of lows a day, which is greatly gratifying. And, uh, yeah, Mark, any, any ways they can reach you

if they want to? Are you going to remain anonymous at this point? I'm going to remain anonymous in my training and, uh, I'll be available one day. He'll be available one day. All right. We'll leave it there. As we end, if you find this podcast helpful and need continued medical education and want to support the podcast growth, please sign up for the podcast. continued medical education yearly membership. For each episode, you can take a short quiz to get CETG1 CME and self-assessment CME. The podcast receives accreditation through a joint providerhip with UCI, who is accredited through the ACME, meaning these CME are good for physicians, physician assistants, physician assistants,

and nurse practitioners. Further, each episode can apply to the MOC Part 2 self-assessment for family medicine, neurology and psychiatry. Other professions like psychologists and nurses can get a healthcare provider certificate to submit to their credentialing board to receive CEUs. I have a link in the show notes and also at psychiatrypodcast.com backslash CME. If you have any questions, shoot me an email at DR atpsychiatrypodcast.com.