Baptist HealthTalk

The Placebo Effect - Mind Over Matter

May 09, 2022 Baptist Health South Florida, Dr. Jonathan Fialkow, Frank Zamora Pharm.D,
Baptist HealthTalk
The Placebo Effect - Mind Over Matter
Show Notes Transcript

There’s a phrase we use to describe the determination it takes to get through an illness or other challenge: ‘it’s a question of mind over matter.’ That’s more than just a saying. Widespread medical evidence has demonstrated the power of the mind to affect our physical state. 

Host, Jonathan Fialkow, M.D., explores the phenomena of the placebo and nocebo effects with Baptist Health clinical pharmacist Frank Zamora, Pharm.D.


Announer:
 At Baptist Health, South Florida, it's our mission to care for you when you're injured or sick and help you stay healthy and fit. Welcome to the Baptist Health Talk podcast, where our respected experts bring you timely practical health and wellness information to improve your family's quality of life.
 
 Dr. Fialkow:
 Welcome Baptist Health Talk podcast listeners. I'm your host, Dr. Jonathan Fialkow. I'm a preventative cardiologist and lipidologist at Baptist Health's Miami Cardiac and Vascular Institute, where I'm also chief of cardiology at Baptist Hospital and chief population health officer at Baptist Health. There's a phrase we use to describe the determination it takes to get through an illness or other challenges. And that's, "It's just a question of mind over matter." But that's more than a saying, there's widespread medical evidence that demonstrates the power of the mind to affect our physical state. One example is the topic of today's episode, which is the placebo effect. Why do certain actions, like taking a tablet or a pill, make things better when there's no active component in what's taking that would otherwise affect our body? And alternatively, why do certain people feel bad effects, side effects, from things that actually have no specific ingredients that would otherwise explain those problems? Joining me today to explore this fascinating phenomena is Frank Zamora, a pharmacist who's the clinical coordinator for drug information at Baptist Health, South Florida. Welcome to the podcast, Frank.
 
 Frank Zamora:
 Thank you so much for having me, Jonathan. I appreciate it.
 
 Dr. Fialkow:
 Frank, and again, I appreciate your time and your expertise. So, let's just start with definitions. Everyone knows, "Oh, it's a placebo effect." Which means, there's nothing really happening, but you feel better. I mentioned the term nocebo, which is the official term. Could you just quickly define for the listeners, placebo and nocebo?
 
 Frank Zamora:
 Of course. And, as you said before, the time goes back to ancient Greece, where mind over matter is a very well-known phrase, where the thought process was that really the mind will affect the health of the body, if you wanted to put it that way. So in regards to concepts, I think it's important to know that placebo is just really a substance without medical benefits, which has not supposed any health effect in the studies or the scientific studies. We refer to placebo as a substance that really the control group actually take and will have no effect whatsoever in whatever it is that we're trying to measure. In contrast to that, nocebo is basically defined as a substance without any medical effect, but which worsens the health status of the patient that is taking that is taking the medication, most importantly, because of the negative belief that the patient has in regards to that specific substance.
 
 Dr. Fialkow:
 So, as you well-articulated, placebo is generally a positive response, someone feeling better, pain going away, et cetera, which we'll talk about. And nocebo might be the perceived negative response. Because again, I think, in conventional wisdom, we call them both placebo effect, but there is a scientific, or at least a well-defined term. So, I tell the story to my patients, quite frankly, and quite frequently when we talk about this, when I was in my training, which is, I say, quite frankly, it startles me, it was 35 years ago. But, I did my medical training in an inner-city hospital in New York City. And we would have a lot of substance abuses coming in and there was withdrawal from narcotics, heroin. And these were young people, and their blood pressure was 220 over 140, and their heart rate was 130. They were in distress. They were in agony.
 
 Dr. Fialkow:
 And now, again, listeners, this was close to four decades ago. We would put an IV in and we'd say, "We're giving you morphine, we're giving you morphine. But we'd be giving them saline." And it's one thing we'll say the placebo effect for them to feel better, but their heart rate came down to normal, their blood pressure came down to normal. And of course, we weren't giving them anything active. So, can you speak a little bit about, what are those conditions? Here's a case of people arriving in agony and pain, and something happened, which didn't just say, "I feel better." But physiological responses. So, where do you see the more common conditions where a placebo effect can take place maybe in a beneficial way.
 
 Frank Zamora:
 So, to that, I think that it would be important to define how this is actually looked at from the scientific perspective. There are really three thought processes here. One is the expectation model, which is really what you're describing, which is the expectation of a patient that basically getting a specific substance will have a certain effect. And this is really true in addiction medicine as you put it. There is a whole ordeal of work that goes into obtaining a legal substance, and that anticipation makes the substance more pleasurable once the patient actually takes it. Another thought process is the reflex model. And that basically goes to condition reflexes in regards to substances or things that we do that consciously or unconsciously will make us feel better or worse. And then, there is a third model, which is the placebo analgesia, which is just basically the first two models intertwined.
 
 Frank Zamora:
 And, the scientific community really believes that there is just not one model over another, that these two or three models, they just basically compliment each other. One experience that I have was, after my residency years, I went to practice at Yale New Haven Hospital. I'm originally from Philadelphia, so I stayed in the Northeast. And, part of my purview was sickle cell anemia, which as you know, is just very complicated patients with extreme pain. And, to talk about the expectations of those patients, looking at the flip side of that, when you tell a patient that is in such distress that you're going to start titrating down opioids because the patient is actually getting better. You will see an uptick on the patient's desire of getting more opioids. And, this is measurable when you have patients for example on PCAs, and you can take a look at the EMR and see how many times they actually click the button. And it's just basically, because there is a level of anxiety that, that communication generates with the patient.
 
 Frank Zamora:
 The same will be truth, if you're talking... That's why communication is so important between clinicians and patients. That level of anxiety going down, based on what the physician or the clinician is telling the patient.
 
 Dr. Fialkow:
 So, it's a fascinating situation that you just articulated. But, I appreciate the original comment. The anticipation of effect can actually help the actual effect be achieved, is what we're saying. And that does come into why pain conditions, depression, you mentioned, sleep. Other medical conditions tend to lend themselves better for a placebo effect, because people wanted to feel better. And then, maybe we can talk a little bit about how that could be abused also. And I say abused, which is certain substances get sold with no active ingredients saying, "Oh, you'll feel better. You'll sleep better. You'll forget less." And the patient wants it to happen. And they actually say, "Yeah, it's really working." But the reality is, there's nothing in it and if we gave them even a sugar pill or something simple, they might feel better.
 
 Dr. Fialkow:
 How much of the anticipation of thinking the substance or the intervention, let's say, makes them better is important? So specifically, if someone knows they've been given a placebo, "Listen, I'm giving you a placebo..." And actually, I remember this ad, I forgot where it was, but there was this new wonder drug that cures everything called placebo. And it was also a drug that caused every problem on the planet, which was placebo. But, if someone's told... For example, the anecdote I gave, if we say, "Listen, we're giving you saline, but you're going to feel better." Would it have the same effect as if they think they're getting something that would actually explain them feeling better? In other words, if they know they're getting a placebo, would it affect the benefit and efficacy of the placebo function?
 
 Frank Zamora:
 In my clinical experience, I think it's important to stratify those patients, because there are certain conditions where that expectation is more pronounced than others. So, anything that is actually related to subjective matters, like pain, for example, or depression, you will see in those cases that the expectation of the placebo effect would be more pronounced. But when you start looking at other conditions, for example, an infection, it would be really hard for me to say that you can just take a placebo and get rid of... I don't know, pseudomonas [inaudible 00:09:11].
 
 Dr. Fialkow:
 A bacteria, sure.
 
 Frank Zamora:
 Right. So, I mean, you really need the antibiotic. The placebo is not going to do anything. So, I think that it's important to basically box in that conditions that are basically measure in subjective items, just per se, pain, depression, things like that, are more prone to the placebo and placebo effect than other conditions. You're a cardiologist, I'll think that you will agree with me that, if you don't give a patient an ACE inhibitor, a patient that has heart failure, that [inaudible 00:09:49] will continue.
 
 Dr. Fialkow:
 I appreciate that. And we've seen that in other areas, it's been established. And a lot of times, even in my practice, when I have a person with a condition and I get them on board as to why we're using the medication, what it's benefits are, and that it's been shown to be effective, I think we're more likely to get a good response, but not necessarily in blood pressure or a blocked artery, but in more perceptions of symptoms and things like that. So I think that's something we can use.
 
 Dr. Fialkow:
 And that comes back a little bit, Frank. And, this is just you and me spit-balling here. It's an ethical issue, because on the one hand, if the goal is to make someone feel better, if the goal is to make someone's pain get better, and we can use something that's safe and cheap and has no functionality, but they get better, isn't that the goal? On the other hand, we don't want to trick the patients. We can't be so patronizing to make decisions for people. So, it does become something that I think our medical ethicists have to define a little further, which would be going back to the original premise, the role of placebos intentionally.
 
 Dr. Fialkow:
 Now, if I give someone that's harmless something and I say, "Listen, people feel really better with this." And I know it's harmless and I know it's cheap, and they feel better, is that wrong? I personally don't do that. I feel I really have to let the patients know what we know and what we don't know about things and they can make their own decisions. But, do you have any thoughts on that? I mean, you are in the clinical support role, do you have any thoughts on that?
 
 Frank Zamora:
 Sure. And, there is very heated debate in regards to health [inaudible 00:11:40], for example, when the patient gives you permission to do a study, whether that's actually enough from the ethical perspective. And I think that I will agree with you, in the sense that, I would not be the type of clinician that would treat the patient with placebo, even if the patient gave me the consent, just for ethical purposes, right? But, there is good information also there to say that, that should not branch out into bizarre treatments or supporting things that we know for a fact that from the medical evidence perspective really have no effect on people and support those treatments, I think that, that's misleading.
 
 Dr. Fialkow:
 So, let's take that to the next component, which is, the nocebo effect, or the side effects, or perceived side effects. And, for the listeners, I think, most people may understand this, but when clinical trials are done, usually there's an intervention, let's say, a new medication, and we're looking to achieve something lower your sugar, give you better sleep, et cetera, et cetera. And the trials are done by taking populations of people and half of them generally get the medication and half get a placebo. Which means they get a pill, but they don't... And the patient, the subject, doesn't know if they're getting the placebo or the active medication, nor does the doctor who's doing the research.
 
 Dr. Fialkow:
 So, if people complain of things, then later on, it's like, "Were you on the placebo or not?" The reason I bring that up is twofold. The main thing is, when you look at the side effects of placebos, and I use that as euphemism, people who are taking nothing, it's a little talc palp tablet, little sugar pill, the complaints they have, "I had diarrhea. I couldn't sleep. I gained weight." They were taking nothing. So again, it shows to that nocebo effect. So, can you speak a little bit in the true clinical scenarios, how that can impact our ability to treat people and manage people?
 
 Frank Zamora:
 Absolutely. And I have two great examples. I was talking to some of my colleagues yesterday, just in preparation for the podcast today and whatnot. And, some of my colleagues actually do medication reconciliation for patients that are getting discharged from the hospital after surgery, whatever have you. And about 30 plus percent of those patients, when the department is about to counsel them in regards to side effects, they say, "No, no. I don't want to hear any type of side effects, because I know for a fact that if you tell me that I'm going to develop something, I will have that in a week, and I'm going to go back to the doctor's office and tell them that I have hallucinations, that I have high blood pressure, that I have syncope, that I have this, and that I have that." That's one. And, that is actually very real. That happens in our practice all the time.
 
 Frank Zamora:
 The other example that I want to bring is, something that goes back to my residency year. So, my second year of residency, we did a study that was a small study open label. There was no blinding or anything like that about drug X. And drug X was supposed to decrease the amount of opioids that the patient will consume after orthopedic surgery on the back end, after 72 hours post-surgery. A very small but significant percentage of the patients that we looked at, we actually saw an uptick in opioid consumption on the back end. And we couldn't understand exactly why that was. And these patients were really away from [inaudible 00:15:13], they were two or three standard deviations away from [inaudible 00:15:17].
 
 Frank Zamora:
 And the only that I can think of is that, there was actually a nocebo effect in there. The patients heard that they were going to be treated with a drug that will decrease opioids in the back end. And what they probably heard was that we were not going to give them opioids to control their pain, which in fact, that was not the case. And that generated a type of anxiety and predisposition, where the perception of the pain was much, much higher in that subset of patients. And therefore, had a clinical impact in an increase in opioid consumption on the back end. So, those are two good examples of what comes to mind when it comes to nocebo effect.
 
 Dr. Fialkow:
 I'm thinking on a, not less important, but much more frequent basis is the use of statins and the medications we use to prevent heart attacks and strokes in high-risk people. And, studies show that, one is 25 times more likely to complain of muscle pain on a statin if they know that statins cause muscle pain, then if they're not aware. So again, it goes back to that anticipation predisposition. Last thing I just want to comment on. And again, I think it's just something that I discuss a lot with my patients, and I want to bring up, and get your opinion, the package insert... And maybe an extrapolation of that, but we go online and look for information. When a package insert lists reported side effects on a medication, it should be noted, that's anything anyone ever complained of on the medication. Half the people in the trials are on placebo. And if they complain of something, it still gets put in the package insert.
 
 Frank Zamora:
 Correct.
 
 Dr. Fialkow:
 So the package insert doesn't say, "That medication causes that." It just says, "Someone in the trial complained of it." And, what I always challenge people is, look at it like a horoscope, because when you read the package inserts, everything will be in there. It'll say, "It causes insomnia." And you'll say, "Yeah, I can't sleep." And right next to it'll say, "Sleepiness." But you don't look at that because you can't sleep. It'll say, "It may cause weight gain." And right next to it, "Anorexia." So, even these things that don't make even sense, but people see what they want to see. The package insert ideally would say, "People on drug, 10% complaint of this. 1% on placebo." Then you can say, "Oh yeah, 10% more likely..." It doesn't show that. So, do you get involved with questions that people have, or having to talk people through what they read on those package inserts, which like I said, it's an FDA regulation, but it really, to me, as a doctor, provides no real value towards disseminating appropriate information. Do you have any thoughts on that?
 
 Frank Zamora:
 For the most part, you don't go too much into the nitty gritty with the patient, unless the patient that I'm treating has a doctor's degree or a higher level of education, mostly because these things are actually reported in the packaging in very high level statistics. But, I think that it is important to also address that, this effect is not discussed enough in our package inserts. As you said, the package insert only just basically gives you a review of the side effects, but it doesn't really focus, or at least, bring into consideration that, there is a placebo effect in here. And there is a set of side effects that perhaps are not related to the actual active principle.
 
 Frank Zamora:
 And I'll give you a great example about this. And I hope this is not two too high level. If you're taking antidepressant X, and you have a number to treat to be 10, that means that I have to treat 10 patients for one to basically benefit from that particular antidepressant. What that means on the flip side is that 9 patients out of those 10 will benefit from a placebo medication that really have no clinical effect whatsoever. And, I don't think, in my opinion, me being a person that reads package inserts for a living, that those things are very well-defined in package inserts. And I think that's important when we actually talk to our patients. As you said that, just to bring about that, yes, there's a multitude of side effects in the package insert description, but perhaps some of these side effects really are not related to the active drug.
 
 Dr. Fialkow:
 I really appreciate, as I said, your ability to articulate these concepts, bring us up to speed a little bit on what's going on and the science behind placebos and nocebos. And I think that's the key takeaway. It's a science, it's real, it happens. There's neurochemical and other components, which make it happen. So, where we go with it as medical practitioners, the use of placebos, the recognition placebos, as well as perceived but not really specific to an intervention, side effects. It's the art of the practice of medicine, in a lot of ways. So again, I really appreciate your time. I enjoyed the conversation. I always love when I learned from our guests. And I learned a bit from you. Any final thoughts? Any final comments? Maybe, in the final comment, I know your title is the clinical coordinator for drug information. Maybe spend a minute at the end just letting folks know what that role entails.
 
 Frank Zamora:
 Okay. And, actually I have a question for you as well.
 
 Dr. Fialkow:
 Sure.
 
 Frank Zamora:
 So, the question is, what do you think the role of teaching placebos and nocebos is in medical school, or any type of graduate school? I don't think that we emphasize that enough. At least I don't remember anything like that on my doctor school years.
 
 Dr. Fialkow:
 So I mean, you're asking a dinosaur here, because it's been some time. But certainly, in speaking to the young doctors that I've recruited and worked with and stuff, it's not in the wheelhouse. I don't think we actually do a good job of teaching real-world discussions with patients. We do a lot on the science and we do an appropriate on empathy, but the real-world conversations you have, pushbacks one we'll get... So, we could do a better job of that. Because again, the understanding and conversations of placebo and nocebo, help you be more patient-centric in your approach. And, if a patient is very like, "I hate medications. I don't want medications. I don't want..." And they may need a medication. I might approach it a little bit differently, give them reassurance, expect a complaint to being on the medication. So, I think, the short answer is, I am sure we could do a better job of it, along with some other things. But I can tell you, practitioners will get exposed to it pretty quickly when they enter practice. And, will start putting it into their thoughts when they start dealing with patients.
 
 Frank Zamora:
 I agree. And for our viewers, the clinical coordinator of drug information, really what it does is, provide clinical information and preferences to any type of internal medicine project. Internal medicine basically means anything. So, I'm here to provide clinical support all the way from the optimization of power plans to research that we actually do in-house, or just basically to identify areas of opportunity for improvement in our clinical practices. That's really my job at Baptist Health.
 
 Dr. Fialkow:
 Great. And it's a great resource to have folks like yourself when we're taking care of patients. So again, I think, we both use the term viewers instead of listeners as a podcast. You don't know, but Frank and I are looking at each other on a Zoom. So I think that's why we get confused, but it's to our listeners. But, again, great stuff to the listeners. Nothing wrong with placebo facts. But when someone's trying to sell you something, that'll make you feel better, or has these miraculous benefits, it's your money, it's probably not dangerous, but it may be a placebo effect, if in fact, you think it's helping you. And again, to our listeners, if you have any comments or suggestions for future topics, please email us at baptisthealthtalk@baptisthealth.net. That's baptisthealthtalk@baptisthealth.net. We'd love to hear from you. Thanks for listening. Stay safe. And thank you very much, Frank.
 
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