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NP Institute Online Learning Hub: Can you share the key unmet needs associated with MDD, particularly regarding partial response and treatment-resistant depression?
Brooke Kempf, PMHNP-BC: Rakesh, when it comes to treating major depressive disorder, our current treatments have kind of left us with a lot of unmet needs. So, some of the things that I think about when I think of the ways that we've been treating depression for a long time, I just think about true lack of efficacy. We're sometimes getting patients better, but not necessarily getting them 'well.' I feel like there's a lot more that we could be done. What do you feel like some of the unmet needs are?
Rakesh Jain, MD: Yeah, it's the best of times. It's the worst of times for our patients. We have more and more treatments, but so many patients are left partially treated. And the truth of the matter is some people just don't get what they're looking for. And Brooke, it's not just depression that bothers me. It's the suffering that they endure as human beings and as family members. And here's the other dangerous thing, Brooke, which is the longer a depression has gone on, the harder it is to eradicate. You've seen that in clinical practice? Yes.
Kempf: Oh, absolutely. Yeah.
Jain: So the unmet need we have is our treatments aren't all that effective. The side effect burden can be quite substantial and I think we are too monogamous with monoamines. We have to break up that relationship.
Kempf: Yeah. We're doing a lot of the same.
Jain: We're doing a lot. That's a nice way to put it. We're doing a lot of the same and getting frustrated in the process. So it's time to reconceptualize depression, maybe not reject what we already knew. But to bring in new thinking.
Kempf: Yeah, I like that.
NP Institute Online Learning Hub: What are the current limitations of traditional monoaminergic therapies in treating TRD?
Kempf: Rakesh, when it comes to our current treatment options, we know we've been treating antide- or sorry, major depressive disorder, the same for a long time with antidepressants that work on monoamines. When you think of that approach, some things come to mind for me in how we could do better. I think the number one thing that I think about is the time it takes for these to be effective when you have a patient in front of you, they're suffering, they're not functioning, they're dealing with depression. By the time they get to you, they've been dealing with it for a while, and then you tell them the treatment is going to take so much time to begin working. I don't know that that gives them much hope when it comes. I know there are many other things with that monoamine approach that we could do better. Can you give us some suggestions?
Jain: Yeah. The very fact that you're dissatisfied and I'm dissatisfied is quite important. Because status quo is damaging to our field. And more than half the patients who receive monoamine-based treatments are not where they need to be. The side effect burden is just profound. So why think differently? I think you articulated beautifully because patients aren't doing well. They want rapid onset of antidepressant activity. I will add one more thing to it, Brooke, which is in addition to rapid, they want a greater degree of improvement and they want it to come with less of a price tag, particularly sexual dysfunction and weight gain. So for all the reasons you have articulated, I'm also adding to it. We are desperately in need of not rejecting the monoaminergic approaches, but expanding above and beyond it.
Kempf: Above and beyond. I like that.
Rakesh Jain, MD, MPH, attended medical school at the University of Calcutta in India. He then attended graduate school at the University of Texas School of Public Health in Houston, where he was awarded a “National Institute/Center for Disease Control Competitive Traineeship.” He graduated from the School of Public Health in 1987 with a Masters of Public Health (MPH) degree. Dr Jain served a 3-year residency at the University of Texas Medical School at Houston. In addition, Dr Jain completed a postdoctoral fellowship in research psychiatry at the University of Texas Mental Sciences Institute, in Houston.
Brooke Kempf, MSN, PMHNP-BC, has worked as a psychiatric nurse at Hamilton Center in Terre Haute, Indiana, since she graduated from Indiana State University with an associate degree in 1994. Her passion for mental health was sparked as she worked as a charge nurse on the Inpatient Unit and continued to grow as she served in their outpatient setting while obtaining her bachelor’s degree from ISU in 1996. She was awarded the 2008 Hamilton Award for Outstanding Staff Member. Kempf was then able to obtain her master’s degree from the State University at Stony Brook of New York and is board-certified by the ANCC as a psychiatric mental health nurse practitioner. She currently practices as the Hospitalist for the Inpatient Psychiatric Unit of Hamilton Center Community Mental Health Center in Terre Haute, Indiana and is an adjunct lecturer for IUPUI’s PMHNP program, teaching and was awarded the 2022 Daisy Award for Extraordinary Nursing Faculty.
Dr Rakesh Jain: My name is Dr Rakesh Jain, and today we're going to discuss how REXULTI is thought to work. REXULTI and antidepressants both interact with some of the same neurotransmitter systems implicated in depression, but in different ways.
Some antidepressants, such as SSRIs, SNRIs, and NDRIs, are reuptake inhibitors that are thought to work on 1 or 2 types of neurotransmitter receptors. SSRIs inhibit the reuptake of serotonin. SNRIs inhibit the reuptake of both serotonin and norepinephrine, while NDRIs inhibit the reuptake of norepinephrine and dopamine. Reuptake inhibitors, such as SSRIs, work by blocking the presynaptic reabsorption of serotonin. SNRIs and NDRIs function in similar ways for other neurotransmitter transporters.
REXULTI is thought to work differently than reuptake inhibitors as a partial agonist and antagonist. REXULTI has high binding affinity to 3 types of neurotransmitter receptors—norepinephrine, serotonin, and dopamine. REXULTI binds directly to the receptor and acts as a partial agonist across some dopamine and serotonin receptors and as an antagonist across some norepinephrine and serotonin receptors. REXULTI acts as an antagonist at norepinephrine ɑ1B, ɑ2C, ɑ1D, and ɑ1A receptors. REXULTI acts as a partial agonist at serotonin 5-HT1A receptors but also as an antagonist at serotonin 5-HT2A, 5-HT2B, and 5-HT7 receptors. REXULTI acts as a partial agonist at both dopamine D2 and D3 receptors. These neurotransmitters exert their effects not only individually, but also by modulating each other's activity.
REXULTI and antidepressants may work together, but in different ways, on some of the same neurotransmitter receptors implicated in depression. Most antidepressants work through reuptake inhibition, while REXULTI is both a direct partial agonist and antagonist of these systems. Please continue listening for additional important safety information.
Transcript:
Dr Jennifer Payne: Welcome to Great Debates and Updates in Psychiatry. The great debates are brought to you by the Psych Congress Network. I'm Dr Jennifer Payne, and I'm here with my colleague, Dr Melanie Barrett. Today, we'll be exploring the connection between major depressive disorder, or MDD, and postpartum depression, also known as PPD, and vice versa. Dr Barrett, why don't you introduce yourself?
Dr Melanie Barrett: Yeah, hi. Thank you for the welcome, and I'm excited to be here today. Again, my name is Dr Melanie Barrett. I am an outpatient psychiatrist in Oklahoma. I work for a behavioral health company, and in my practice, I focus on women's mental health, interventional treatment options, treatment-resistant depression, and education. So, I'm really excited to be here to talk about this important topic of postpartum depression.
Dr Jennifer Payne: Great. Well, thank you for doing this. I'm Dr. Jennifer Payne. I'm a professor and vice-chair of research in the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia. I'm a reproductive psychiatrist, and I specialize in the management of psychiatric disorders during and after pregnancy. I also conduct research and have been focused on biomarkers of postpartum depression. So, thank you for joining us. Before we begin, we have a quick poll we'd like you to respond to. You'll see some questions on your screen. Please go ahead and respond to those questions now.
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Hello, I'm Dr Charles DeBattista, a professor of psychiatry and behavioral Sciences at Stanford University. I'm also the director of the Depression Research Clinic and Director of Medical Student Education in Psychiatry at Stanford.
Question: What are some of the unmet needs that persist for patients with major depressive disorder?
Dr Charles DeBattista: Despite the fact that we have lots of treatments that help patients, there's still an important subset of patients that don't respond to or necessarily tolerate the treatments that we do have. Many patients have significant side effects with the available treatments, and many others don't respond, even though we've tried multiple medications and various devices and so forth. In addition, access is still a problem for some patients. New branded medications tend to be expensive. Many insurance companies don't allow those kinds of branded medications.
In addition, technologies like transcranial magnetic stimulation, so forth, are sometimes not available to many patients, particularly in rural communities. Medications, especially oral medications, take a long time to work if they're going to work. If they don't work, it means trying an additional medication, which also takes time, and maybe trying multiple medications in a series. We don't have great biomarkers as of yet that help us predict response to treatment. These are all things, though, that progress is being made on as we speak.
Q: What are some signs of treatment-resistant depression that clinicians should be on the lookout for? Which tools are available to make screening more consistent and effective?
Dr DeBattista: There isn't a consensus definition about treatment resistance. Investigators have used different criteria for treatment resistance. One common criteria is the failure of 2 or more adequate medication trials. That means adequate dose and adequate duration. Now, the way we monitor patients typically is with a number of standard depression scales. These can include things like the Montgomery-Asberg Depression Scale or the Hamilton Depression Scale. None of them are perfect, but at the same time, they do quantify the level of response or lack of response, and so it's what we tend to use in the clinic as well as our investigations.
Charles DeBattista, DMH, MD, is currently professor of psychiatry and Behavioral Sciences at Stanford University School of Medicine. In addition to serving as director of medical student education in psychiatry at Stanford, he also is the director the Depression Research Clinic and Co-Section Chief of the Mood Disorder Clinics.
Dr. Stephen Chan and Dr. Madhukar Trivedi explore the role of neuroplasticity in MDD and how neuroplasticity can be impacted by emerging digital therapeutics for the treatment of major depressive disorder.
Saundra Jain, MA, PsyD, LPC discusses evolving perspectives on depression.
Watch Drs. Chepke, Jain, and Shirikjian as they delve into the current treatment landscape for major depressive disorder, including a look at newer and emerging treatments.