Charles R. Marmar, MD, is the Peter H. Schub Professor of Psychiatry and Chair of the Department of Psychiatry at NYU Langone Health. He also serves as Director of the Center for Precision Medicine in Alcohol Use Disorders and Post-Traumatic Stress Disorder (PTSD) and as Executive Director of the Steven A. Cohen Military Family Center.
Topics covered:
Internationally renowned for his expertise in PTSD for over 25 years, Dr. Marmar's focus ranges from combat-related conditions in military veterans to PTSD in refugees and earthquake victims. He has served on multiple committees and scientific advisory groups at the national level for both the Department of Veterans Affairs and the National Institute of Mental Health (NIMH) and as counsel to the VA Medical Centers, fire departments, disaster response teams and police departments, including the NYPD.
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
Charles R. Marmar, MD, is the Peter H. Schub Professor of Psychiatry and Chair of the Department of Psychiatry at NYU Langone Health. He also serves as Director of the Center for Precision Medicine in Alcohol Use Disorders and Post-Traumatic Stress Disorder (PTSD) and as Executive Director of the Steven A. Cohen Military Family Center.
Topics covered:
Internationally renowned for his expertise in PTSD for over 25 years, Dr. Marmar's focus ranges from combat-related conditions in military veterans to PTSD in refugees and earthquake victims. He has served on multiple committees and scientific advisory groups at the national level for both the Department of Veterans Affairs and the National Institute of Mental Health (NIMH) and as counsel to the VA Medical Centers, fire departments, disaster response teams and police departments, including the NYPD.
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
[00:00:00] DR. THEA GALLAGHER: Welcome to NYU Langone Insights on Psychiatry, a podcast for clinicians about the latest in psychiatric research. I'm Dr. Thea Gallagher, a clinical psychologist and assistant professor at NYU Langone. This podcast is driven by a single question: What do clinicians need to know about the latest psychiatric research? I hope that by asking this question, we can help reduce the seven-year gap between research and new treatments, bringing relief to patients faster. Each of my guests is a leader in their subfield of psychiatric research. On this, the first episode of the podcast, I'll be talking with Dr. Charles Marmar. Dr. Charles Marmar is the Lucius N. Littauer Professor and Chair of the Department of Psychiatry, NYU Langone Health, and the Director of the Center for Alcohol Use Disorder and PTSD. We begin by talking about PTSD.
Your area of research, which has been around PTSD for many, many years, what have you come to understand are the challenges with the advancement and diagnosis of PTSD?
[00:01:02] DR. CHARLES MARMAR: Some of the challenges are that it's a young field compared to other disorders. As you know, the disorder was only formally incorporated into the diagnostic system of the American Psychiatric Association in 1980. I was part of that process. So compared to the understanding of schizophrenia, bipolar disorder, depression, and so on, PTSD, although historically it's been written about for thousands of years, it's relatively new as an area of formal academic discipline.
What are the problems? First, as with other psychiatric disorders, we rely for diagnosis primarily on what the patient reports to us of their experience and what we can observe of their behavior. For example, are they jumpy or easily startled if they are surprised unexpectedly? Do they report things like nightmares, flashbacks, and other symptoms? And what family members or others can tell us about the person and how they changed after they were exposed to a traumatic event. But we lack objective, laboratory-based ways of making the diagnosis. And in the case of trauma, because trauma is often very sensitive and stigmatizing, for example, childhood sexual abuse, adult sexual assault, combat in which you've taken enemy combatants lives—these are very difficult things to talk about. Patients therefore may be very reluctant actually to tell us what they're experiencing, or in a minority of cases for reasons of compensation, litigation, service connection, or otherwise, they may exaggerate or dramatize their problems. So the first thing is we can't solidly rely on self-report. We need to move beyond it to some objective ways of characterizing PTSD. Whether those are brain-imaging findings or voice quality studies or blood chemistry studies, or others, we need to move into the era of modern laboratory medicine.
Second problem, PTSD is very heterogeneous. People who are traumatized share in common the fact that they've been through often life-threatening and very disturbing experiences affecting themselves or others that they've observed or feel close with. But among traumatized patients, there's very wide variety in how they experience their traumatic symptoms. When you compare those who've been, who were exposed three weeks ago versus 30 years ago, it varies tremendously even among those who all shared a common experience and returned from war one year ago when we studied them. So heterogeneity is a huge problem.
And the final thing is, the way treatment guidelines have been developed, they've been fundamentally developed in terms of average expectable responses. So on average, certain forms of psychotherapy, like cognitive behavior therapy, are helpful to patients. On average certain medications like antidepressants are helpful. But the problem is the patient in the room with you or me is not average. They're a unique individual with a unique history, with unique genetic vulnerabilities and uniquely different expressions of their traumatic stress syndrome. So the major problem is we lack objective ways to diagnose and we lack criteria by which to personalize treatment. Analogy: 50 years ago, 80 years ago, somebody had an infection in their blood. We didn't have the tools to actually identify the organism, and even if we did, we wouldn't know which among the various treatments available would be the best one. Now if a patient comes into the hospital today with a blood infection, we culture their blood, we test it against a whole range of antibiotics, and we find those that are most effective against the known organism. In the diagnosis and treatment of PTSD, we're a century behind that.
[00:05:46] DR. THEA GALLAGHER: Why is this such a problem? Like you said, we know that there are treatments that work, there are some treatments that work for some people. Are you talking about a subset of people who this isn't working for? What is the difficulty with this heterogeneity with regard to ultimate treatment and intervention?
[00:06:07] DR. CHARLES MARMAR: For example, two out of three war fighters, either as active duty or as veterans, one of the largest groups of traumatized patients we care for, do not respond well to the so-called gold-standard treatment, prolonged exposure therapy. They do not remit. They either have some partial improvement or no improvement at all. So we have tremendous problems. Patients often don't respond to antidepressants. They develop side effects from them so that in fact, for any given individual, it's very difficult to develop a clear, patient-specific treatment plan that will maximize the safety and effectiveness of this treatment for this person at this time. So we lack precision. We lack understanding of the wide heterogeneity. Let me give you one example. We know from recent research that I collaborated on with a colleague at Stanford, Dr. Amit Etkin, that among both civilians with PTSD and veterans with PTSD, there's a sizable subgroup, 30-, 40-plus percent, that have significant cognitive impairment. That cognitive impairment is seen, for example, in tests of cognitive functioning, such as problems with attention, concentration, and working memory, and it's also seen in tests of brain imaging where we interrogate cognitive circuits using functional brain imaging. Among those who have significant cognitive impairment, among PTSD patients with those impairments, they showed zero benefit to prolonged exposure therapy. That's a huge problem.
[00:08:03] DR. THEA GALLAGHER: And what is your hunch as to why, and specifically veterans, are not responding well?
[00:08:09] DR. CHARLES MARMAR: Well, probably the cognitive variant subtype is more prevalent among veterans. We know there are probably higher rates of ADHD among veterans, that affects their cognitive functioning. We know that there are higher rates of traumatic brain injury among veterans. We know that veterans are often recruited from more vulnerable groups that have very difficult childhood histories, often lower educational attainment, often higher levels of adverse childhood experience, and often histories of more brain injury before they're deployed to war, and then they're at risk for further neurocognitive insults in the course of their military service. And so probably one of the reasons why CBT, which is a form of learning, is less effective with veterans than in some civilians is that they have impairments in learning.
[00:09:07] DR. THEA GALLAGHER: So understanding this, what are your thoughts or suggestions, or what are you seeing coming down the pike, or some research that you've already done, that would improve our diagnostic tools or the way that we diagnose?
[00:09:19] DR. CHARLES MARMAR: So this is very exciting. We're just at the very beginning, and I'm delighted you asked me that question. So we've been conducting a number of studies to try to address this problem. I'm fortunate to be funded by the NIH to direct a Center for Precision Medicine in Alcohol Use Disorder and PTSD. And the goal is to address these problems. First of all, it's to develop more objective tools for diagnosing PTSD, particularly for high-throughput screening for PTSD in primary care in military or civilian practice. And second, ways to reduce the heterogeneity by creating meaningful subtypes of PTSD. I'll talk about that. And finally, we're doing a whole series of studies to try to determine who will be and who will not be a likely responder to a psychological or biological treatment for alcohol use disorder alone or in combination with PTSD. And we have a lot of exciting ideas about that. We're developing blood tests for screening for PTSD. We're gonna develop next generation tests using neuronal exosomes, which are present in blood, but actually reflect the genetic activities of brain cells such as neurons. We are developing voice tests. We're on a podcast together, right? We don't have visual imagery to share, but our listeners can very rapidly detect our enthusiasm, our energy, and our interest in this topic strictly from our voice quality. And what we're doing in a collaboration between NYU and a group of biomedical engineers at Stanford Research Institute, a wonderful group in Menlo Park, California, a group of engineers that in there have a few minor accomplishments in their track records, such as developing Siri for Apple and such as, for example, writing the natural languaging software for Dragon Naturally Speaking, so we can do voice dictations. So these are among the finest speech engineers in the world, and we're working with them to develop objective ways to analyze speech segments to detect for the presence, for example, of PTSD and depression compared to healthy controls. So those are some of the examples. Looking at blood biomarkers, looking at voice biomarkers.
We're also looking at brain circuits in my collaboration with Dr. Etkin at Stanford and Dr. Moh Milad at NYU. We're looking for signature brain-circuit features, which will help us not just separate PTSD from TBI as an example, but actually partition PTSD into different subtypes: PTSD with prominent cognitive impairment, PTSD with prominent depression, PTSD with severe anxiety comorbidities such as panic disorder. We're gonna create these different subtypes of PTSD, and the reason is we believe the treatments will be quite different for these subtypes. The final thing, which is very interesting, is we're working with a group of advanced applied mathematicians at NYU and elsewhere to develop computational methods to predict who will and will not respond to a particular treatment. And I can give you some interesting examples.
[00:13:14] DR. THEA GALLAGHER: Well, let's hear the examples.
[00:13:16] DR. CHARLES MARMAR: Okay, great. So, we published a paper recently built on some work that the National Institute of Alcoholism and Alcohol Abuse (NIAAA) published a major study, which they concluded several years ago. And in that study they recruited 370 approximately participants with alcohol use disorder. Okay. And this was not a PTSD study. This was a study of heavy drinkers. People who had multiple heavy drinking days per month. These were people who met criteria for alcohol use disorder. And these patients were randomly assigned to one of two treatment conditions—a novel drug called gabapentin enacarbil, it's an anticonvulsant drug, mood-stabilizing drug, or a placebo. And the trial was completed—I believe it was a 10 site trial—and the results were somewhat disappointing. The results were that the drug did not separate from the placebo in terms of its overall effects. So, the average improvement in the gabapentin group was very similar to the average improvement in the control group. And the conclusion was, in a sense, a failed trial for a novel medication. We took the following point of view, we examined the outcomes in the gabapentin group and the placebo group, and found that while on average they were similar, that they were highly variable. Just by looking at the distributions of the scores, you could see some of the participants did extremely well on gabapentin, some didn't change much, and some got worse, as an example. So, working with professors Eugene Laska and Carole Siegel here in our Department of Psychiatry at NYU, these are mathematicians working in psychiatry, they developed some very advanced computational models that said, can we identify the subgroup of patients that respond to gabapentin? And the answer is yes. And then can we compare them with people in the placebo group that share their general characteristics and see whether gabapentin is better than placebo in the responders compared to a subset of the controls that were similar to the responders? And the answer was yes. Thea, we found an amazing result. The result was although gabapentin on average is not better than placebo, if the patients were heavier drinkers before treatment, if they had lower not higher levels of anxiety and depression, and if they had higher levels of behavioral and cognitive impulsivity, they did really well on gabapentin. Which was really very interesting when you think about it, because those are the impulsive patients who might do better with a mood regulating anticonvulsive drug.
[00:16:36] DR. THEA GALLAGHER: And so, taking that information, and if we were gonna synergize that or think about that from a clinical perspective, how would that be helpful for someone who is, who is a psychiatrist practicing today?
[00:16:49] DR. CHARLES MARMAR: Well, for example, if you refer me a patient with alcohol use disorder, and they're very heavy drinkers, they have relatively low levels of anxiety and depression, and they're very impulsive in their decision making, I would be inclined to start them on an anticonvulsant drug rather than an antidepressant drug.
[00:17:12] DR. THEA GALLAGHER: So this is something that people can take this data and use it today.
[00:17:18] DR. CHARLES MARMAR: Right today! Let me give you another example, which I think you'll find very interesting. There is preliminary data to suggest that among men and women who are depressed, we're shifting now from PTSD to clinical depression, among a diverse group of men and women who are depressed, in general, women as a group will tend to do somewhat better on the commonest class of antidepressant drugs, selective serotonin reuptake inhibitors, drugs like Prozac and Zoloft, Paxil, Celexa, and Lexapro, compared to the men on average. And the men do a little better on drugs that have a mixed-receptor characteristic, drugs like Wellbutrin and Effexor, which affect more than just the serotonin system, they affect other brain transmitters, with the caveat that that holds true mostly for women from the onset of puberty to menopause, and is not true for women after menopause, in which case the women after menopause tend to respond better to the same antidepressants that men respond to, drugs like Wellbutrin and Venlafaxine. And even more interesting, if at the time of menopause women are placed on estrogen replacement therapy, that's controversial, has some risks and benefits, but if they are, they continue to respond well to SSRIs. So clearly the and Dr. Moh Milad and our department has been studying this issue of estrogen levels and their effects on brain circuitry and on stress and depression. And there are major differences, obviously, between men and women in this area. And there may even be differences in women across the menstrual cycle. So it's very, very interesting. But the point is, again, this is an opportunity to personalize treatment. So that not to assume one size fits all. So if you refer me a 40-year-old man who's depressed, I'm going to start that person on a drug like Wellbutrin or Venlafaxine. If you refer me a 40-year-old woman, I'll probably start on an SSRI and then move from that point.
[00:19:42] DR. THEA GALLAGHER: Yeah and it seems like we're moving away from, I think in some ways there's a lot of great benefits to manualized treatments or interventions, medications that work for a large group of people. But what you're saying is that there's still a large group of people for which these gold-standard treatments do not work, and we need to be doing research and implementing the findings in a more personalized medicine approach.
[00:20:06] DR. CHARLES MARMAR: Correct. The problem with the so-called gold-standard treatments, or to put it more broadly, the problem with treatment guidelines, which are published for every psychiatric disorder, is that they tend to recommend first-line, second-line, and third-line treatments based on average responses in the population. But a given patient that you refer to me for care might respond much better to a third line treatment given their particular characteristics. Let me give you for our listeners, let's use a different analogy. Let's for a moment, step outside of psychiatry and step into the world of cancer therapeutics. When I was in training in medical school, we fundamentally had, it was like psychiatry, treating cancer. We had several so-called gold-standard treatments. You probably remember what they were, surgery, chemotherapy, and radiation. We had treatment guidelines that said, for this tumor, start with surgery, and if needed, move to radiation. And if the patient still continues to have difficulty, add chemotherapy or the reverse of that depending. Those were the guidelines, right? Now, if you practice, if you treat a man with prostate cancer or a woman with breast cancer following those guidelines, you will be involved in malpractice now. Why?
[00:21:39] DR. THEA GALLAGHER: Well, because they need something that more applies to their specific cancer.
[00:21:43] DR. CHARLES MARMAR: Correct. And those are mostly, now, it's not that we don't use these other treatments as adjunctive. We do, and they're helpful. I'm not disparaging those treatments, but what I'm saying is we, what the real interest and the real progress is in genomically specific monoclonal antibodies. So that if someone is struggling with let's say prostate cancer, the drug recommended for them might actually end up being a drug that was developed for lung cancer. It's not important. The organ's not important. It's the genomics that are important. If that person's prostate cancer expresses certain genomic features, they're going to do better with a completely different class of drugs. That's precision medicine. In the same way, if a patient is experiencing, let's say, gets COVID and then develops a severe secondary pneumonia, which can be life threatening, you don't want to treat them on some first-line, second-line, third-line treatment algorithm of so-called gold-standard treatments. You want to grow out the organism and you want to test it for culture and sensitivity, and you want to give that person the combination of antibiotics that are specifically directed at their infection in the right dose, at the right time to save their life. That's moving from general medicine to precision medicine, and psychiatry and psychology as fields are about 50 years behind. And this isn't just a problem in psychiatry. Think about it in the field of psychology. Think how many so-called evidence-based treatments there are for depression or anxiety or PTSD, which one to start with? How to personalize treatment? Who's going to do better, for PTSD for example, with prolonged exposure therapy versus cognitive therapy, versus psychodynamic therapy versus supportive therapy? They will do differently based on their psychology.
[00:23:58] DR. THEA GALLAGHER: And with these subtypes that you're talking about too, what's the next step there? Is it understanding maybe the relationship between the PTSD and the panic, or which one is primary or how to treat them with adjunctive treatments to the gold standard. What's the thought about, once we have these subtypes or can identify them, then what is the implication for the treatment intervention?
[00:24:21] DR. CHARLES MARMAR: So the first thing is we want to validate the subtypes and we want to use, how will we do that? We recently received a very large grant from the Department of Defense to do that in 13,000 subjects, both veterans and civilians, in a seven site collaboration. So we're in the, we're just launching that project now, and I hope you'll invite me back to give our results in a few years when we have them. But the first thing we want to do is we want to see, can we validate the subtypes? What does that mean? It means can we identify them and are those subtypes relatively stable in different patient populations? So if we study male war fighters and women sexual assault survivors, we should find the same subtypes. They might be in different proportions, however. That's the first thing. Second, can we show that for any given subtype that its clinical features, cognitive functioning, neurocognitive testing, molecular features in their blood or urine or elsewhere, and their brain imaging features form a coherent pattern for that subtype, which is different for another subtype. Let's say we accomplish that and let's say we end up with three subtypes, PTSD with prominent cognitive impairment, PTSD with prominent depression, and PTSD with a severe comorbid anxiety and alcohol use disorder. Say those come out as the, those are just hypotheticals, chances or maybe PTSD with prominent dissociation, those are likely candidate subtypes. Let's say we validate them. The next thing we would do is we would use those subtypes as stratifiers in clinical trials, and we would determine how to match treatment against the subtype. So, the treatment for those with neurocognitive impairment will probably be different from those with comorbid panic disorder.
[00:26:32] DR. THEA GALLAGHER: I think for people listening who are clinicians, some of this can sound overwhelming, right? It's easier or it feels nice when you know, okay, this patient is presenting symptoms of PTSD, we can treat them with the gold-standard treatment, give them the confidence, we have the confidence. And at the same time, what you're talking about I think is also probably attractive to providers—giving the patient exactly what they need. And so, how can we like, and obviously a lot of research needs to be done before we can take some of this into clinical practice, but what can people do or adjust or think about if they are in practice today, thinking of people in a precision medicine way?
[00:27:16] DR. CHARLES MARMAR: Wonderful. Well, the first thing is, I am a great believer in hard conversations. What do I mean by a hard conversations? I mean an open, honest, and direct acknowledgement of what's true and what we don't know. Okay. You have to start by being willing to give up our position of authority. Because the problem is the field like psychiatry and psychology has been dominated by charismatic figures with great confidence and passion in their approaches. The only problem is they're not well-validated. Okay? So the first thing we have to do is we have to recognize the limitations we have in fields like psychology and psychiatry. First limitation is how effective are we on average? And if you look across most of the psychiatric disorders, stress, traumatic stress, anxiety, depression, schizophrenia, bipolar disorder, ADHD, and other treatments, the rule of one thirds applies pretty well. What do I mean by that? On average, without personalizing treatment, about one out of three of the patients we're referred does well or very well with one of the first or second line treatments. About one in three struggles and does somewhat well only after multiple attempts to treat and combinations of treatment that can take months or years. And about one in three is largely treatment refractory and struggles with chronic illness for a long period of time. So that's on average across our treatments. So the first thing we have to recognize is using one size fits all treatment and treatment guidelines, it's very difficult to get past the rule of thirds. That means that there's huge room to help the two out of three patients that we care for that don't quickly and efficiently respond to a first-line treatment. That's the first thing to say.
The second thing I would ask our clinicians to think about and those listening is that our field is often—the care plans we give our patients is often influenced more by the training we received and the mentors we have than anything objective about the characteristics of the patients and their treatment response. So, if I'm trained as a cognitive behavior therapist and a patient is referred to me with stress, anxiety, or depression, I will attempt to give them a mainstream CBT treatment. If I'm trained as a psychoanalyst, I will be inclined to give them a psychoanalytic treatment. If I'm trained as a psychopharmacologist, I'm likely to go through whatever medications. If I'm trained as a neural interventionist, I might start with transcranial magnetic stimulation or something else. Now, we actually had some fun one time earlier, and we actually did a randomized test of this. We created a hypothetical patient, presented this patient to our trainees, and had the trainees consult with five different people that were supervising them to see what the recommended treatment would be. And as you would guess, the treatment plan was driven heavily by the experience, professional training, professional identity, passion, and interest of that particular supervisor. And so with five different supervisors, we got five different treatment plans. Now that's remarkable.
Let me create an analogy. Imagine that you're a cardiologist and I refer you a patient with an arrhythmia, atrial fibrillation, and you shop around the treatment plan with five different prominent cardiologists. You do not get five treatment plans. You get one treatment plan in a certain sequence based on the b—but first what you, well, the first thing you get is they will say, well, that patient has to go through a series of tests. They have to have EKG, they have to have stress echoes, they have to have other tests. And after we look at all the biomarkers, we will come up with an optimized treatment plan, but it won't be based on the fact that when they were in training, their supervisor thought beta blockers were really cool. That is not how arrhythmias are treated. Okay. But unfortunately in our field, that's often how the care plan evolves based on the style, taste, history, and identity of the clinician. And obviously that is not responsive to the individual. In fact, that treatment is being organized around, in some ways, the comfort of the clinician, not the needs of the patient.
[00:32:29] DR. THEA GALLAGHER: And it sounds like what you're saying is from a diagnostic perspective and a treatment perspective, it's too subjective and it needs to be more objective, more measured outside of the self-report of the patient, and outside of the training of the clinician.
[00:32:46] DR. CHARLES MARMAR: Correct. First thing is we need objective ways to make the diagnosis. Second thing is we need ways to, to, um, decode the enormous complexity and heterogeneity of our conditions. They're probably 10 kinds of depression, not one. And third, we need ways to be able to predict who will and will not respond to any given treatment. Prolonged exposure therapy is a valuable treatment for a subset of patients with PTSD. The question is, who are they, and more importantly, who are they not? Because if we impose a one-size-fits-all care plan on our patients, we will end up with a patient treatment mismatch more commonly than not. And what's the cost of that? Prolonging the suffering of the patient, or maybe exposing them to unnecessary side effects. Can I give you a very dramatic example?
[00:33:57] DR. THEA GALLAGHER: Mm-hmm.
[00:33:57] DR. CHARLES MARMAR: Okay. We published a single fascinating, "we" meaning members of my department, not me, and members of our depart—Faculty of Neurology, published a fascinating, in 2013, single-case study of a patient with severe persistent treatment-resistant or treatment-refractory depression. The patient had been ill with severe clinical depression for many years. Now, in the course of that treatment, they receive—in the course of their illness depending on who they consulted with, they received treatments that were recommended to them, so they saw psychotherapists, psychologists who recommended psychological treatments. They all failed. They saw psychopharmacologists who recommended multiple medications alone and in combination. They all failed and they even were hospitalized at a point and received electroconvulsive therapy because they were so ill. And this is over a period of many years, the patient was exposed to multiple different treatments, and did not respond to treatment. And given all the so-called gold-standard first, second, and third line psychological and biological therapies for depression. Now, at a certain point, the patient came to us and we did a high level consultation, and a concern was raised that this patient might have a form of a brain inflammation called encephalitis, caused usually by the body's own antibodies attacking part of their brain, a condition called autoimmune encephalitis. And there was sufficient concern in this particular case that something very un—the patient had brain imaging, they had other tests, but in the end it was unclear what the nature of the problem was. And it was felt that the illness was so severe that it was warranted to do a fine needle biopsy of this person's brain. Something that's not done in psychiatry but is done in neurology in selected cases to rule out certain neurological disorders. This was done, a small sample of brain tissue was taken from a safe area in the right front part of the person's brain. It was sent to pathology and the pathology specimen came back, massive inflammation of the brain. That patient was placed on a novel anti-inflammatory medication that crosses the blood-brain barrier, and for the first time in several decades, they had significant clinical relief from their depression.
[00:36:53] DR. THEA GALLAGHER: Yeah. And I think it's not, I think the moral of this story, and one that I think we're seeing across many different arenas of medicine is that the patients that aren't improving with the gold-standard treatments deserve the investigation of what's actually going on and what they need to get better.
[00:37:13] DR. CHARLES MARMAR: I would be more radical. We should have looked for an inflammatory source for this patient's depression from day one, because we do know a subset of patients with depression have an inflammatory disorder. Sometimes you can even detect that from some simple peripheral blood tests. For example, C-reactive protein and several others where you can see a general marker of inflammation in the blood. Sometimes you need to go further than that, but my point is different. My point is we need to get to a point. We, we don't want to go through all the first- and second- and third-line so-called gold-standard treatments and expose this patient to a whole series of treatments that are A ineffective for that individual and B have side effects and complications when we could have ways to understand that there is a subtype of depression, which is inflammatory, determine what it is and start with an anti-inflammatory, not end with it years later.
[00:38:23] DR. THEA GALLAGHER: Yeah it reminds me of the phrase, ‘When all you have is a hammer, everything looks like a nail.’ And that's what we're trying to move away from because it's a little caveman-like.
[00:38:33] DR. CHARLES MARMAR: To a cognitive behaviorist, everything looks like PE. To a psychoanalyst, everything looks like an unconscious conflict. We have to be very careful in our field, because our field is very compartmentalized, it has very strong histories and theories, and it has devoted practitioners.
[00:38:55] DR. THEA GALLAGHER: Yeah. And I think one of the larger themes that would be helpful for people practicing as clinicians, too, and providers is that, like you started off this conversation with having the hard conversation, and I think many people, many providers wanna feel confident in the treatments they're disseminating or in the treatment program or the path that they have, that they're collaborating with their patient on, and I think in some ways you're asking people to feel a little bit less confident. Which might make their patients feel less confident. And how can this be a positive thing though, or what's a healthy way for a clinician to take what you're saying and see it as something maybe positive for both them and the patient in the future? Because I think we're talking about—we have alliances to maybe what we've been trained in, and I think sometimes for good reason, I think all of us wanna help people. We want them to feel better. I don't think anyone would do that—
[00:39:54] DR. CHARLES MARMAR: Well, let me give you an example. Fifty years ago, 60 years ago, the predominant paradigm in psychiatry in America was psychoanalysis. Psychoanalysts in their training at that time were very reluctant to use medication. Even though they were doctors and trained to use them in general medicine, they went to medical school. But if they became analysts, they would analyze patients. And those patients, some of them struggled. They might be in an analysis for five, six, seven years or longer. They might gain some greater understanding of their own character and the interactions with their family, their family dynamics. They might have some deeper understanding of their personal conflicts, but their level of anxiety and depression may be exactly the same or greater than it was when they started the treatment seven years earlier. And over time, the analysts had to step back, be less confident that that's the primary major approach and learn to combine psychotherapy with psychopharmacology as needed. I think, Thea, these are all deep lessons in humility. We have tools, but they're tools. They're not—I think we have to step away from tools as a form of professional identity. Cognitive behavior therapy is not a professional identity, it's a tool in the approach to caring for patients with stress, anxiety, and depression. And if that tool is applied to the right person at the right time with the right problem, it will be very effective. If it's the wrong person at the wrong time, we may be condemning that person to years of unnecessary suffering. Let me give you another example. A patient is depressed and is, I remember having this conversation with Don Klein, who was one of the fathers of psychopharmacology in this country, brilliant psychopharmacologist, also trained as an analyst. And, it happens I was trained both in psychopharmacology and psychoanalysis, so we were, we were having this conversation. Somebody refers a patient who's depressed, and they have conflicts. Now, the question then becomes ethically, would you start a course of five, six, seven years of psychoanalysis, or would you start three weeks of an antidepressant and see if their depression clears, and then decide what to do next?
[00:42:29] DR. THEA GALLAGHER: And the answer is?
[00:42:31] DR. CHARLES MARMAR: And the answer is you will do the right thing for the patient if you don't form your identity as I'm an analyst and I have to cure illness through psychoanalysis, or I'm a cognitive behavior therapist and I cure PTSD by prolonged exposure therapy. No, I'm a clinician and my job is to release suffering, and I will do what is important for that patient if it's in my repertoire and if it's not, I'll refer that patient.
[00:42:59] DR. THEA GALLAGHER: Yeah. And it's simplified in this statement, but moving away from clinician-centered or clinician-focused to patient-focused precision medicine, better diagnostic tools, which can inform better treatment protocols, which can help people as unique as they are. That, like you said, they are not as homogenized as maybe we would like for treatments to be effective. But I think it can be exciting to think that there will be new ways to both diagnose and treat that look a little bit closer and a little deeper and a little more nuanced at the individual.
[00:43:35] DR. CHARLES MARMAR: I think so, and I think in 20 years you and I will be practicing our art the way cardiologists treat arrhythmias.
DR. THEA GALLAGHER: Which would be great.
DR. CHARLES MARMAR: Which would be fantastic for our patients and good for you and I too because as clinicians working together, we will learn to more deeply understand other approaches and embrace a collaborative team approach to healing as opposed to staking out our turf.
[00:44:03] DR. THEA GALLAGHER: Yeah. And that could be a whole other podcast on how we can move away from that culture in this field. But we're starting here. So it's promising and it's exciting and you’re obviously very connected to the cutting edge research that's happening that's gonna inform this next wave.
[00:44:24] DR. CHARLES MARMAR: Well, just to conclude, one of the reasons I'm so interested in when I was in training, I was almost the only person I knew who was simultaneously training in neuropharmacology and psychoanalysis. At the time it seemed an anathema, you were supposed to decide, are you an analyst or are you a biological psychiatrist? I was equally interested in both and agnostic about them. I thought they're both fascinating and both potentially helpful. So from day one, it was my idea to try to personalize the treatments.
[00:44:57] DR. THEA GALLAGHER: And day one, it sounds like it forced you to be probably more open-minded because of doing something that was that other people weren't doing.
[00:45:04] DR. CHARLES MARMAR: One thing for sure, the human mind and the human brain don't care about our guilds at all.
DR. THEA GALLAGHER: So continuing to be curious and figure people out on that individual level. All right, well this has been a great conversation, and thank you so much.
DR. CHARLES MARMAR: Okay. It's been a pleasure.
[00:45:19] DR. THEA GALLAGHER: Thanks so much again to Dr. Marmar for that conversation. On the next episode of NYU Langone Insights on Psychiatry, I'll be speaking with Dr. Dan Iosifescu about the treatment of severe mood and anxiety, including novel treatments such as ketamine and other glutamatergic drugs and magnetic stimulation.
If you enjoyed this episode, be sure to rate and subscribe to NYU Langone Insights on Psychiatry on your podcast app. For the Department of Psychiatry at NYU, I'm Dr. Thea Gallagher, see you then.