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Hello, everyone. Uh So today we are going to dive right in and talk about Red Pill versus Blue Pill. Uh For those of you matrix fans out there uh from, from that movie that might be af familiar tagline. Uh and it represents some of the uh opportunity and also dilemma when it comes to medication selection for individuals uh experiencing major depressive disorder. And so today, we're gonna talk about uh how to evaluate the effectiveness of some of the first line antidepressant treatments and select an optimal medication for your patient uh who is receiving treatment for major depressive disorder. And we're gonna start with a case of a patient I treated uh a few years ago. Uh We're gonna protect the innocent and call her Sally for the purpose of this conversation. Sally was a 44 year old female uh Haitian immigrant, first generation Haitian immigrant uh living here in the US uh very high functioning. Uh She described uh a set of values related to achievement and perfectionism and having to pull herself up by her bootstrap, so to speak, uh due to her relatively disadvantaged background. So having to make a name for herself. So she excelled academically through school, uh received AAA scholarship to college uh at a prestigious university and then subsequently received her master's degree uh and currently worked uh as an executive um for a local health healthcare company uh in the city where she was receiving treatment. And so Sally, at the same time, um had struggled with depression and anxiety over the years. Um initially with uh postpartum depression uh following uh I believe her, her first child's uh birth. Uh And so that was the um beginning of her mental health treatment experience. Uh And at the time of her treatment with me, um she had been, you know, well over 10 years into her mental health treatment journey. Um with that initial pregnancy and postpartum depressive episode, she responded well to sertraline. Uh but not surprisingly, as many of you um have experienced with your patients. Uh her response to sertraline waned over time and reached a plateau. And so she began some of the trial and error of medication selection. So, upon coming to us, um she uh had worked with her outpatient provider um and had a trial of buPROPion uh as well as um a low dose of buspirone for augmentation without much success. And so she had just discontinued those medications prior to coming to me, uh and my team for additional treatment. So we have the benefit of starting with the with a clean slate, so to speak. And in reviewing her history, the fact that she responded well to sertraline, which is an SSRI um we elected on uh another SSRI trial. Uh in this case, Escitalopram. In addition, we were um uh working with her on cognitive behavioral therapy um as well as more targeted vocational support as it relates to some of the challenges she was facing on her job and um stress points there. Uh Additionally, uh Sally received ATMs which is transcranial magnetic stimulation. So as you can see a very comprehensive and broadbased approach to the treatment of her depressive symptoms at the time of her treatment with us as far as her treatment progress. Um One of the things that we uh um like to do is what's called evidence-based treatment, both with medication selection and also with treatment response. So using clinical rating scales, uh validated tools such as the MOS in this case, the Montgomery Asperger depression rating scale and seeing that Sally started off at a 30 which is uh kind of a more moderate to severe level of depression. And then over time, it went down to a milder level and by the time of her finishing treatment with us over an eight week time frame, um her symptoms were were quite mild. She continued in uh T MS even after her treatment with me directly uh to have ongoing kind of maintenance of of her treatment response. Uh and stabilization. Sally also had a successful return to work uh upon completing our treatment program. Um and more internally, I think even uh more, more valuable than some of those things is how she felt about herself. So it improved sense of resilience, practicing more acceptance and flexibility. One of the things that kind of came with her perfectionism and high achievement was a lot of self IOD pressures, a lot of should statements and expectations that she would placed on herself, feeling like she's gotta be superwoman at work. And also super mom back at home with her three kids and with her husband and through her treatment course, realizing that that wasn't a sustainable plan and her coming to a place where she's able to take a step back, extend herself more compassion and more grace and just practice more acceptance and flexibility. Her being able to ask for help um from her husband uh and from her kids who are older and allowed her to be more, more present uh with her family and enjoy the quality time that they had. And also for her Sally, uh her, her spirituality and faith background was something that was very important to her. And not surprisingly, that had kind of waned during her depressive episode, she felt more distant from God and more kind of numb when it come uh when it came to spiritual um uh themes. And she was able to tap back into that uh through uh improvement of her depressive symptoms as well. So we're gonna zoom out now from, from Sally's case and look at a kind of a more big picture assessment on antidepressant medications that we use as first line and how to have that conversation with our patients and select, uh, um, an appropriate option, um, to help them. So, uh, what you're looking at on this slide is, um, a landmark study that came from the Lancet. It was published in the Lancet back in 2018, multiple, uh, treatment sites. Thousands, in fact, tens of thousands of patients, uh, in the study looking at individuals with major depressive disorder and not only how did they respond to medications, but what were some of the side effects or tolerability of those medications? So, on that left panel, um, what you're seeing is, um, the response or the effectiveness of medications. Uh, if you're seeing, uh, data on the right side of that column with the blue squares and the lines, those are saying that, uh, those medications were more effective than placebo when it came to, um, treating depressive symptoms. And in a reassuring way, you'll see all of the medications that are on that list on the right side of that line demonstrating effectiveness, uh, better than, than, than placebo. Uh, and so that's, that is reassuring in many ways that, uh, in some sense, there's not a quote unquote wrong option to choose when it comes to first line antidepressant treatment. Um, I know one of the uh beauties of treating depression is that there are a lot of medication options. One of the challenges in treating depression is that there are a lot of medication options. Uh but hopefully, this adds some reassurance that um many uh uh of the treatments that are on the market now have proven to be effective uh in the treatment of major depressive disorder. Now, in the right side of that slide, uh we're looking at uh our ability or also known as acceptability in this case where we're looking at the dropout rate. So, uh, in which, in which cases did patient stop the medication due to side effects or other difficulties tolerating the medications. Um, again, uh, on the right side of that, uh, midline, those medications, uh, are better tolerated, meaning fewer side effects, fewer drop out rates. Uh, and then those on the left side indicating less tolerated or more side effects, more likely to discontinue the medications. Now, of note, uh, even though you see most of those things cross the midline and even some to the left, um, those were not a statistically significant result, meaning it didn't kind of meet the, um, research threshold of statistical significance. However, we can still say on a case by case basis, there's some clinical significance in terms of as we go down the list and more to the left, those medications, those antidepressants being, uh, less tolerable or more prone to having side effects So again, using that to kind of guide decision making for medication selection for our patients uh who are receiving treatment. Uh And as I referenced in Sally's case, uh one of the things that is helpful for tracking uh symptom uh severity as well as response to medication is using some form of a validated tool or screening tool or rating scale for depressive symptoms. I've selected a few for the purpose of this conversation today um that I use in my practice and that my colleagues use that are pretty user-friendly uh and easy to do and give some objective measurement related to depressive symptoms and also as a surrogate to response to medication. So what you see on the screen is called the P HQ nine, the patient health questionnaire nine. And as its name indicates, it's a series of nine questions uh ranging from not at all to nearly every day. And you're asking your patients on uh about how they've experienced each of these symptoms over the past couple of weeks. So very easy to use, very accessible um free of copyright. So you're able to use it in your practices even now to help assess initial severity of depressive symptoms as well as tracking their response to medications or treatment over time. Another example of that is the Hamilton Depression rating scale, as you'll see here, this one a little bit more involved. And in Sally's case, what we use was the Madras uh the Montgomery Asberg rating scale, again, even more involved in the screen, you're just seeing a snapshot of this one. But I believe this one has 15 questions um uh for a total score of uh uh 60 then assessing the, the severity. So again, uh not a strong preference in terms of which scale to use. Um try each of them out figure out which one fits best with your practice and with your patient population, which one feels, you know, the most user-friendly to you, uh each of them are reliable and well established uh in the literature. So now talking a little bit more about patient specific factors for medication selection. So you're in the office, the patients there in front of you, you've taken a history and now you're having a conversation about what to do as far as medication treatment for major depressive disorder. So a few things that um I listed here on the slide to help guide that decision making and the, the context that I really wanna emphasize is that this is not a transactional experience, you know, II know we live in a digital age where with, with, with A I and other things, it's easy to kind of plug into an algorithm and, and get a response. But I think part of the art of medicine is the human connection and the emphasis on the doctor, patient relationship or the provider, patient relationship. And uh one of the things I remember hearing during my residency training was love me, love my medicine, right? So in, in the sense that uh patients trusting you, feeling safe with you, feeling like you have their best interest at heart and that you really wanna see them thrive, that will make them more likely number one to take the medication and to kind of trust in its benefits. Um We know that the placebo effect, meaning someone's belief about something influences their influences their experience of it. And so in this case, we wanna leverage the positive aspects about the therapeutic relationship to so secure more buy in into the treatment. And so again, at the level of the medication decision itself, you wanna think about side effect profile, right? Are there some dealbreakers for the patient? You know, you may have some patients that say doc I just, you know, I cannot gain weight. I've struggled with body image or with um you know, issues related to my weight over the years. So any medication that has a higher risk of weight gain, that is a nonstarter for me. So again, you wanna, you know, consider that or other similar side effects that could be dealbreakers for your patient. Next, uh we wanna consider drug drug interactions, particularly for um patients uh who have mental health disorders. We know that those patients are at increased risk of medical disorders as well. So many times our patients have comorbidities, whether it's heart disease or diabetes or thyroid conditions or chronic pain. Uh, we know that these things come in packages. So, uh, antidepressant medications are not the only medications that our patients, uh, are usually taking. So we wanna be mindful of what other medicines are they taking and what are the potential, uh, potential interactions of those medications with the ones that we're prescribing? Also taking a history. What's worked in the past, what meds have they been on in the past that worked well that they're interested in retrying or which ones have they tried that did not work well or were terrible and they just keep them off the list. So, taking a good history, uh, and understanding the previous medication trials that our patients have had can also be helpful. Uh, next, there's some good literature that indicates that a first-degree family member who's been on a certain medication, their response to that medication, uh, is informative to what your patient's response could be to that same medication. So, understanding the genetics and kind of, uh, uh, um, heredity around not only mental illness but treatment response as well. And so if they have a parent, a sibling who, um, is on a medication and having a good response that would be reasonable to consider. And conversely if they have a parent or sibling or relative, uh, who's on a medication and had a very poor response, something to consider as well. Um, one of the things that is available nowadays is pharmacogenetic testing um for patients to kind of understand um what their genetics are and how they may respond to certain medications. Again, I don't promote that as the end all be all for how to prescribe, but it can be a tool. It can be useful information in certain cases to help guide medication selection. Next, we wanna know about uh the level of adherence as well as cost or financial factors. So, uh if a patient has a history of stopping medications, um then sometimes considering uh long-acting injectables or uh even trans transdermal patches or other other things, if someone has significant nausea and can't tolerate pills, that's, you know, considering other routes of administration and then, uh particularly here in the US, really thinking about cost and affordability. So, depending on health insurance coverage, uh and um what their allowances are for certain medications, we want to at least factor that into the conversation when it comes to medication selection. And the next, once you started the medication and we're in, you're in the followup phase. Here are some things to consider to assess someone's response to that antidepressant. And again, using this in the context of a healthy therapeutic treatment relationship, the more that they trust you, the more that you built a good rapport with them, the more likely they are are to come to that follow up appointment. And also to be honest with you, uh with your experience on that medication. Sometimes uh patients experience some level of shame or guilt when they stopped the medication or they aren't taking it exactly as prescribed, but they may tell you something different out of fear of not wanting to disappoint you or have you be upset with them. So the more you can create a safe space to allow for an honest uh communication, both ways that leads to better outcomes for our patients. And so really leveraging the doctor patient relationship, clarifying expectations on the medication and the timeline for response. One of the, you know, somewhat unfortunate things is that many of our antidepressants don't necessarily work immediately. Um You know, there's some uh you know, great data and research around treatments such as ketamine that have a, you know, more kind of rapid onset. But for your typical uh uh oral antidepressant medication, you're looking at somewhere between 2 to 4 weeks to assess an initial response and sometimes upwards of 6 to 8 weeks for uh for an adequate trial. So setting that expectation on the front end that, that, hey, you know, this is gonna take time. I know you wanna feel better yesterday, but I need you to be patient with this process in the same way that the depressive symptoms probably have been lingering for months or not years by the time that they come to us for treatment. Framing that expectation that yes, 2 to 4 weeks can feel like a long time, but it's relatively small in comparison to the months or years of suffering that they've been dealing with. So just being clear, uh and being honest with that expectation on the front end that it's not a quick fix, but it's worth sticking it through to have the possibility of that relief and that benefit in the weeks ahead. Also looking at uh scores on some of those evidence-based tools, whether it's the Madras or uh the Hamilton D or the P HQ nine collateral from family members is huge. Uh We know that our patients do not live on islands by themselves, right? They are in, in community and in relationship with other people. So if they can bring a spouse or a loved one to their appointments or family members, um to offer that additional perspective of how they're doing that can really be valuable uh and enhance the the outcome and the treatment experience. And then secondly, you know, looking at some other secondary sources of information, whether it's calling the pharmacies to check on refills, uh or looking at the attendance log to the appointments if the patient has missed 2 to 3 appointments in a row and you haven't heard from them, that may be a sign that they're not doing well or they're, they're not, you know, following up with the treatment uh as prescribed. And so reaching out uh and just being proactive as much as you can to reengage them uh, in that process and offering reassurance that because there are so many antidepressant options, we're usually not stuck on whatever we pick first. Right. They're not locked in forever on that medication if it's not working for them. So, being, um, open on the front end, letting them know that medication changes are common and can happen throughout the course of treatment. It's not, um, a sign of their failure or that they've done something wrong. It's sometimes a part of the process. So just being clear with those expectations as well. All right. I hope this has been helpful and informative and thank you for your time and attention today.