Hello, and welcome to today's Emerging Topic webinar, Advances in Obesity Treatment, Medication Management for Psychiatrists. My name is Vishal Madan. I serve as the Chief of Education and Deputy Medical Director at the American Psychiatric Association. I'm honored to be your moderator for the session today. Thank you all for joining. We are delighted, we are thrilled to have Dr. Vikas Gupta as our esteemed speaker today. Dr. Gupta is the founder and CEO of Wellness Psychiatry, PC. He's a quadruple board certified in adult psychiatry, child and adolescent psychiatry, obesity medicine, and community and public psychiatry. His practice uniquely integrates mental health and weight management to provide comprehensive clinical care. Dr. Gupta's career includes serving at the MGH Massachusetts General Hospital and as a faculty member at Harvard Medical School. Currently, he holds leadership roles at the APA, including Vice Chair of the APA's Annual Meeting 2025 Scientific Program Committee, Co-Chair of the Posters Subcommittee there, and Co-Chair of the Courses Subcommittee as well. Additionally, he's an active member of the APA's Council of Research and the AA CAHPS, the American Association of Child and Adolescent Psychiatry's CME and Clinical Essentials Committees. Dr. Gupta's commitment to psychiatric education has earned him numerous accolades, including the Child Pride Fellowship, the AdPerts IMG Fellowship, and the AA CAHPS Educational Outreach Program Awards. His work focuses on empowering psychiatrists with knowledge of emerging treatments like medications related to obesity medicine and to enhance holistic and effective patient care. We are excited for what promises to be an engaging and informative session. Thank you again for joining us. And with that, let's begin. Next slide, please. A quick note, today's webinar is designated for one and a half AMA Category 1 credits for physicians. Participation credit will be available for 90 days following today's session. Next slide, please. For today's presentation, we have available closed captioning. To enable, hit show captions at the bottom of your screen. For a full transcript, click the arrow and select view full transcript to open the captions in the side window. Next slide. A quick note about Q&A instructions and how to participate. Please feel free to submit questions at any time by typing in the question area located at the lower portion of your control panel. Again, it's in the question area located in the lower portion of your control panel. We will dedicate the last 10 to 15 minutes of the presentation to answer your questions. Next slide. And without any further delay, let's get started. I'll hand it over to Dr. Vikas Gupta. Thank you so much, Dr. Madan, for a wonderful introduction. And thank you all for joining in today for a seminar on Advances in Obesity Treatment, Medication Management for Psychiatrists. My name is Vikas Gupta, and I'll be your presenter today. And I'd love to talk to you more about different aspects of obesity management as it pertains to psychiatry. I have no relevant financial disclosures with any commercial interest to disclose. In terms of my objectives, today, I'll be reviewing pharmacological treatments for obesity, especially with relevance to psychiatry. We'll understand the safety and efficacy profiles of the newly approved obesity medications. We'll look at key psychiatry considerations when prescribing these medications. We'll learn how to integrate obesity medications into comprehensive care plans, as well as enhance your clinical decision-making based on the latest in obesity medication management. Starting off, in terms of obesity prevalence, the prevalence of obesity in adults in the United States is about twice as much as in children, about 42.4% in adults versus 21.5% in children. Now, obesity is considered when the body mass index is 30 or more for BMI. And about 10% of Americans also deal with extreme obesity, which means a BMI of 40 or more. In terms of the pool prevalence for obesity in severe mental illness, the global data shows that the pool prevalence is about 26%. Remember, this is a pooled global data, so this is a little different from the US prevalence of obesity. Prevalence of obesity plus overweight is about three in five in the patients with severe mental illness. Patients based on baseline obesity, it increases risk of depression by one and a half fold. In terms of recommendations, there are several recommendations throughout the US and several guidelines. One of the major ones is the US Preventive Services Task Force's guideline, which recommends screening all adults for obesity with BMI. Overweight is diagnosed when the BMI, which is weight in kilograms divided by height in meters squared, is between 25 to 29.9. And obesity is diagnosed when the BMI is 30 or higher. If a patient has a BMI of 30 or higher, the US PSTF recommends offering or referring patients to intensive, multi-component behavioral interventions for weight management. Weight bias, as we know, is incredibly prevalent in our society, and this is also true in the medical settings. Fewer than 50% or less than half of the patients with obesity are overweight. With obesity, we see weight loss counseling from their primary care physicians. Not only that, weight bias also leads to poor rapport and engagement between physicians and patients. Clinician counseling on weight reduction has shown to cause and lead to modest weight loss. Thus, lack of counseling is a major barrier in overweight or obese patients in receiving important health recommendations. A psychiatrist, due to the nature of their practice, which heavily relies on rapport and relationship building, can thus play a major role in addressing this practice gap for obesity counseling. It can also lead to effective integrated care where psychiatrists can consider and address obesity in discussion with their patients, primary care physicians, and other specialists. There are two effective techniques shown to have demonstrated evidence and efficacy for obesity management. These communication techniques involve the 5A framework and the motivational interviewing techniques. Both these techniques are associated with increased patient confidence around making dietary changes and achieving better results for losing weight. The 5A's framework is a model that can be used to help patients manage their weight by promoting behavior change. The 5A framework starts with the ask, which is the first component of this, asking the patient about their weight and readiness to change their behavior. Next is to assess wherein patient's height and weight is assessed to calculate their BMI. Also, their medication records are reviewed and patients are assessed for comorbidities and other weight-related conditions. The next step is advice where patients are provided with education and counseling on the benefits of weight loss, as well as informed about the different treatment options for obesity. The next step is agree wherein discussion is had with the patients to set specific, measurable, attainable, relevant, and timely goals, also known as SMART goals. The next step is assist where patient is assisted with lifestyle changes and weight reduction strategies. So, obesity, as we all know, is correlated with several health conditions, including coronary heart disease, stroke, type 2 diabetes, cancers, pancreatitis, depression, anxiety, binge eating disorders, etc. Weight loss has shown to have several health benefits. Losing even a few pounds or losing 3 to 5% of body weight may result in improved blood glucose, lower triglycerides, improved glycemic index, and reduces risk of type 2 diabetes. Weight loss of 5% or around 5% lowers blood pressure and reduces LDL and increases HDL. More weight loss in the range of 5 to 10% may lead to decreased need for medications for blood pressure, diabetes, and cholesterol. Sometimes losing higher percentage of weight, 20 to 25% may be needed to improve cardiometabolic outcomes related to comorbid conditions related to obesity. We all know that several medications contribute to weight gain, of which several medications indicated for medical conditions are notorious for weight gain. These include insulin and several diabetes medications, steroids, HIV medications, including NNRTIs and protease inhibitors, contraceptives, including progesterone, beta blockers, and antidepressants and antipsychotics. As you can see in this image, many adults take one or more of these medications, which can contribute to overweight and obesity. Talking about psychiatric medications especially, we know that antidepressants can contribute to weight gain, and we know that the risk is somewhat higher with the TCAs, amitriptyline, citalopram, which is an SSRI, of course, and then clomipramine, fluvoxamine, metazapine, nartriptyline, peroxetine, and phenylzine, which are really on the higher side of the risk for weight gain, versus some other medications which have lower risk for weight gain, which include bupropion, floxetine, zuranolone, esketamine. Talking about antipsychotics, several psychiatrists and primary care physicians worry about patients being on antipsychotics due to their weight gain potential. Now, highest on the risk of weight gain are clozapine and olanzapine, whereas some of the other medications, including the xanomeline traspium, which was the most recently approved medication, has a lower risk and is actually believed to be weight neutral. Similarly, lumatipirone, which is also a relatively newer approved antipsychotic medication, is also lower on the risk of weight gain and is believed to be somewhat neutral. Luracidone is also categorized as somewhat weight neutral, though I've had some patients who gained some weight on luracidone. Another medication that is low on this risk is thezeprasidone, which is used by a lot of psychiatrists for the weight gain risk, as the weight gain risk with this medication is certainly on the lower end. In terms of mood stabilizers, we know that they're also associated with weight gain, the highest risk being for valproate as well as lithium. Weight neutral medications include lamotrigine or topiramate. So if you have to consider a mood stabilizer for a patient with risk of weight gain or to prevent further weight gain, lamotrigine or topiramate may have a stronger buy-in with patients. So there are several predictors of significant psychotropic associated weight gain. Some of these include younger age, efficacy of the psychotropic medication, low baseline BMI, longer duration on the drug, earlier in the course of the illness, and greater than 5% weight gain during the first month of treatment. There are several treatment strategies that can be used for prevention and treatment of psychotropic drug-related weight gain. The first, it starts with measuring a patient's weight and BMI, considering the waist circumference measurement, and also recommending lifestyle behavioral modification and dietary changes. Treating psychiatry comorbidity associated with weight gain and prioritizing weight neutral or less obesogenic medications, following metabolic monitoring guidelines while on psychotropics allows for earlier detection of weight gain and earlier initiation of interventions for weight gain. Starting metformin early, if starting someone on antipsychotic is another intervention that is shown to be effective. For established psychotropic drug-related weight gain, the first line of action is to consider switching to a medication with a less weight gain potential and start adjunctive metformin. The second step would be to consider starting a GLP agonist. However, GLP agonists can be prioritized if there is a comorbid type 2 diabetes or non-alcoholic fatty liver disease as a part of shared decision-making with the primary care physician, endocrinologist, or obesity medicine physician. So, there are some limitations of strategies to limit psychotropic-associated weight gain. These include a somewhat modest magnitude of effects from most medications studied to counter drug-associated weight gain. These include metformin and topiramate. Also, adverse effects from some of these medications, for example, topiramate has been associated with worsening cognition or sedation. Metformin is somewhat associated with GI upset and diarrhea. And also, that antipsychotic weight gain can continue for more than one year, but even when some of these agents are used, there is not enough data on the long-term necessity, safety, and efficacy of those medications that have been studied so far. And also, there's one more challenge that most of the studies on GLP-1 agonists have focused on weight and glycemic control in non-psychiatric patients. Talking about weight-loss interventions in psychiatry and using medications in psychiatry, one of the key things to note is, as much as we can, we should try to use weight-neutral medications where clinically indicated, for example, for depression using medication like velbupropion, and also using weight-neutral antipsychotic medications when possible. The other thing would be to initiate metformin to prevent weight gain if an antipsychotic is prescribed. Historically, metformin has been prescribed somewhat later, but new discussions and new evidence is pointing out to starting metformin even at the very beginning after starting an antipsychotic medication to mitigate the risk of weight gain. Obesity is associated with approximately 25% increase in odds of mood and anxiety disorders. It frequently co-occurs with binge eating disorder and night eating syndrome. In case you've not heard of the night eating syndrome, it's an eating disorder characterized by excessive food intake in the evening and late evening. It's also associated with an increased risk of characterized by excessive food intake in the evening or night time. It involves consumption of at least 25% of daily calories after dinner and frequently nocturnal awakenings to eat. It's classified as other specified feeding or eating disorder under the DSM. It involves recurrent episodes of night eating after awakening from sleep or after the evening meal. Awareness and recall for eating is present, which differentiates this from sleep-related eating disorder. So this is distinguished from binge eating disorder because the amount of food consumed in the night is not necessarily objectively large, nor is there a loss of control over food intake required. This syndrome does cause a significant distress and functional impairment and is not explained by other causes. And several patients with bariatric, short bariatric surgery, about one in six individuals have noted to have NES, which is a night eating syndrome. Also, we know that SMI, including schizophrenia and bipolar illness have higher rates of obesity. And we do know that weight management does improve both physical health and psychiatric outcomes. Now, it's very important to understand that depression and obesity have a bidirectional relationship. This bidirectional nature creates a feedback loop where one condition exacerbates the other, making both harder to manage. Addressing one condition, for example, obesity without considering the other, which is depression, may lead to suboptimal outcomes, highlighting the need for integrated treatment strategies. Lifestyle interventions, psychological therapies, and possibly medications need to be tailored to both conditions simultaneously. This understanding of bidirectionality is crucial for psychiatrists when devising treatment plans for patients dealing with these conditions. This is a treatment pyramid for obesity, wherein multi-component lifestyle interventions are the first intervention attempted. These interventions target nutrition, physical activity, and behavioral change, and patients typically lose about 2% to 8% of baseline weight with these interventions. A key part of this intervention is weight management. This intervention is multidisciplinary teams with mental health and other clinicians, frequent clinician-patient contact, and accommodation of patient preferences. Next in this pyramid are anti-obesity medications, which can lead to a weight loss of 5% to 20%. This is further followed by endoscopic procedures, which also could cause weight loss between 10% to 20%. And on the top of the spectrum is surgery or surgical procedures and bariatric surgery, which could lead to 25% to 40% weight loss. Very significant and important to remember from this weight treatment pyramid is that patients who are overweight or have obesity usually prefer lifestyle interventions and anti-obesity medications rather than surgery or endoscopic procedures. However, patients with severe obesity and multiple comorbid health conditions could receive significant benefit from endoscopic procedures or surgery. In terms of candidates for drug therapy or medication management for obesity, this can be considered for patients who have a BMI equal to 30 or more or a BMI of 27 to 29.9 kilogram per meter square with weight-related comorbidities, which include diabetes, hypertension, or dyslipidemia, or in whom a weight loss goal of 5% of total body weight at 3 to 6 months of comprehensive lifestyle hasn't been met. Individuals needing to lose 10% to 20% of weight, such as those with cardiometabolic conditions, may also require anti-obesity medications. It's also important to remember that BMI is a screening tool. Therefore, base circumference should also be assessed while ascertaining candidates for obesity. This allows for confirmation of excess body fat consistent with the diagnosis of obesity, as opposed to an elevated BMI just due to a higher muscle mass. So, some important facts about anti-obesity medications. Upon initiation of anti-obesity medications, patients should be made aware of some facts about them. First of all, not every drug works for every patient. Individual responses could vary significantly. Secondly, when the maximal therapeutic effect has been achieved, weight loss could plateau or further weight loss could cease to happen. This does not mean that the medication has stopped working. It just means that further weight loss will need additional steps or strategies. Also, if anti-obesity therapy is discontinued, weight regain is expected. Several factors make it difficult to achieve and maintain weight loss, and these include changes in energy expenditure and hormonal mediators of appetite, all of which favor weight regain. Given these factors and the fact that obesity is a chronic disease, the recommendation is generally to use anti-obesity medications long-term for weight loss maintenance if they are well-tolerated and have led to clinically meaningful weight loss, which is believed to be more than 5% weight loss. So several medications are considered for weight gain and obesity. These include metformin and topiramate, especially in psychiatry. Some other medications have been FDA-approved in this domain, and some have been studied in conjunction with psychiatric medications like semidorphin with olanzapine. Now, important to remember that there are several categories of anti-obesity medications. They are categorized firstly into centrally acting medications, which primarily reduce appetite. These include phentermine that increases the release of norepinephrine in the hypothalamus, could lead to side effects like dry mouth, headache, constipation, and insomnia. Next in this line of centrally acting medications is phentermine topiramate that also increases norepinephrine and augments GABA. Main side effects of this medication include paresthesias, constipation, dry mouth, and dysgeusia. Third centrally acting medication is naltrexone bupropion that stimulates the pro-opioid melanocortin neurons. It inhibits opioids in the mesolimbic dopamine system. The naltrexone part inhibits opioids in the mesolimbic dopamine system, and bupropion blocks the reuptake of dopamine and norepinephrine in the various brain regions. The side effects of the naltrexone-bupropion combo include nausea, constipation, headache, insomnia, dizziness, vomiting, and dry mouth. The next category of anti-obesity medications, these include the nutrient-stimulated hormone-based medications. These are the more popular medications, which include the GLP-1 agonists, including liraglutide and semaglutide. The GLP-1 agonists, they act centrally in the brainstem, hypothalamus, and reward centers of the brain to increase glucose-dependent insulin secretion, inhibit glucagon secretion, and delay gastric emptying. Tirzapatide is also part of this group of medications, with the difference being that it is a dual GLP-1 and a GIP agonist. These medications stimulate the metabolic effects of the enteropancreatic hormones via the gut-brain axis. The side effects of these group of medications are primarily nausea, vomiting, diarrhea, abdominal pain, and constipation. The next category of anti-obesity medications include intragastrointestinal medications, first of which is Worlistat, which blocks digestion and absorption of up to 30% of fat. It deactivates pancreatic and gastric lipases that facilitate fat absorption in the small intestine, and thus results in a caloric deficit but has no effect on appetite. Contrast this with the centrally acting medications and GLP-1 agonists, which both cause appetite reduction. Main side effects of Worlistat are oily fecal spotting, fecal urgency, and steatorrhea. The next group of intragastrointestinal medication is an oral cellulose citric acid hydrogel, which expands and fills the stomach. Taken before a meal, it expands to occupy 25% of stomach volume. It creates a sensation of fullness and enhances satiety. Side effects do include diarrhea, abdominal distention, constipation, and abdominal pain. Now, first-line medication for weight loss management include the glucose-dependent insulinotropic polypeptide. It's also called GIP, slash GLP-1 agonist, terzapatide. Terzapatide, this dual-receptor mechanism, has shown to have the most efficacy of most medications that have been approved for weight loss or obesity management. Research studies have shown that patients on terzapatide have lost more weight than those taking semaglutide. The starting dose is usually around 2.5 mg subcutaneous once weekly, and the dose is titrated gradually by 2.5 mg every four weeks. And the maintenance dose for terzapatide is 5 to 15 mg once weekly. It's available in brand names called Munjaro and ZepBound. Munjaro is approved for type 2 diabetes. However, ZepBound is the one which is approved for weight management in adults with a BMI of 30 or more. It's also approved if you're overweight and have another health condition, including high blood pressure, high cholesterol, or type 2 diabetes, or obstructive sleep apnea. Sometimes the insurance may not cover Munjaro or ZepBound depending on the coverage and whether they are being prescribed as indicated or as off-label. Next is GLP-1 agonists, which are actually the most popular and most commonly prescribed medications for obesity. These comprise semaglutide. Semaglutide is started at a dose of 0.5 mg subcutaneously once weekly and gradually titrated every four weeks to 0.5 mg, 1 mg, 1.7 mg, and eventually 2.4 mg weekly if needed. These titrations happen after every four weeks. Studies have shown similar efficacy for oral semaglutide as well for weight loss. However, oral semaglutide is not approved by FDA yet for obesity. It is marketed, though, as ribelsis, which is FDA approved solely for managing type 2 diabetes. Semaglutide is marketed under Wigovi for adults with obesity or overweight with at least one weight-related condition, such as hypertension or type 2 diabetes, and is also marketed as ozempic primarily for type 2 diabetes. Both are available for subcutaneous injections. Important to remember that semaglutide, when marketed as ozempic, is not FDA approved for obesity management. Wigovi is also approved in pediatric patients 12 and older for obesity and weight loss if they meet the criteria. Maintenance dose recommended for semaglutide is 2.4 mg once weekly or 1.7 mg. If one dose is missed and the next scheduled dose is more than two days away, administer Wigovi as soon as possible. If one dose is missed and the next scheduled dose is more than two days away, 48 hours later, do not administer the dose. This is sometimes seen in clinical practice when patients will call you and they will inform you that, hey, I missed to administer my subcutaneous injection, and what do I do now? So repeat for semaglutide if a patient misses injections. If one dose is missed and the next scheduled dose is more than two days away, administer the medication as soon as possible. If one dose is missed and the next scheduled dose is less than two days away, do not administer the dose. And resume dosing on the regularly scheduled day of the week. If two or more consecutive doses are missed, resume doses as scheduled, or if needed, reinitiate from the lowest dose. Next up is liraglutide, which is also known as sexenda and is approved for chronic weight management in patients with obesity or who are overweight with a BMI equal to greater than 27 kg per m2 and have a weight-related comorbid condition, which could be hypertension, type 2 diabetes, or dyslipidemia. Some patients may not tolerate the GLP-1 agonists or trizepatide and prefer oral medications. This may also happen when the insurance refuses to cover those medications for off-label indications or other reasons, or if the patients are unable to pay for these medications themselves. These medications include phentermine topiramate or listed phentermine and naltrexone bupropion. Coming up to metformin. Metformin and antipsychotic weight gain. Metformin has been the most frequently studied and used medication in antipsychotic-associated weight gain. It has shown to be actually more effective to plateau than reverse the antipsychotic weight gain clinically. Studies, however, have shown a decreased weight of 3.27 kg compared to placebo for antipsychotic-associated weight gain. Dosing typically starts at 500 mg twice a day with gradual upwards titration up to a maximum of 2,000 mg per day. This is overall well-tolerated. Some patients may report diarrhea, stomachache, or bloating. It's important to monitor renal function while someone is on metformin. A risk of lactic acidosis is about 4.3 per 100,000 patients. There are some considerations before starting metformin. It should not be prescribed to elderly above the age of 80 or to medically ill patients with renal failure, heart failure, etc. A baseline medical assessment including weight, comprehensive metabolic panel, lipid profile, vitamin B12 levels, and hemoglobin A1c should be done. Counseling should be done about the need to take it with food. Heavy alcohol use should be avoided and recommended. A multivitamin should be taken daily while taking metformin. Some psychiatrists or physicians prefer to use the extended release version, daily with the largest meal for one week and then go up to 1,000 mg a year daily for one week. This can sometimes be helpful for patients who do not like the BID dosing. Also important to remember, diarrhea is one of the more common side effects with metformin. If a patient reports diarrhea and is on immediate release formulation, they could be switched to the extended release formulation. Also remember that metformin can decrease B12 levels in the body. Therefore, it's important to check vitamin B12 levels at least once a year. Coming up to topiramide. Six RCT studies demonstrated a weight decrease in the topiramide group by 5.3 kg. Metformin in 14 RCT studies showed a weight decrease of 3.36 mg per this paper by Hillier et al. Thus, more research has been conducted in metformin. However, the weight loss data that we see is stronger for topiramide with more meaningful weight loss reported in patients treated with topiramide. So thus, topiramide should also be strongly considered where and when indicated. Clinical trials have also looked at adding semidorphone to olanzapine, and this is actually approved as a medication for management of SMI and schizophrenia. Olanzapine, as we know, is notorious for weight gain. Semidorphone, an opioid receptor antagonist, has been combined with olanzapine to address some of these concerns. And it has shown to lead to lesser weight gain in studies, including the ENLIGHTEN2 study, wherein also the cardiometabolic risk factors were noted to be decreased. However, we need more evidence as more studies need to be conducted. One thing to remember with the semidorphone is that some patients with semidorphone will report of increased somnolence, so that's an important side effect to remember. However, some patients who have found olanzapine efficacious for the management of their mental health conditions and really need to stay on that, the current evidence points towards using the olanzapine-semidorphone combination to mitigate weight gain as well as the cardiometabolic risk factors. Coming up with GLP-1 receptor agonists, they are primarily secreted by the GLP-1 peptide is secreted by the L cells in the intestinal mucosa. It leads to reduced blood sugar by insulin secretion in the presence of elevated blood glucose. It reduces appetite by stimulating the satiety center. It also slows down gastric emptying and GI motility. These are some of the more commonly available GLP-1 agonists. These include liraglutide, which are branded as Victoza, and FDA-approved for glycemic control in type 2 diabetes. The next one version is Saxenda, which is essentially the same as Victoza. However, the FDA approval for this one is for chronic weight management in adults with BMI over 30 or with comorbidities with BMI over 27. The next one is semaglutide, which is marketed under three names. The first one, which I spoke about earlier, is an oral version, which is Ribelsis, which is FDA-approved for glycemic control in type 2 diabetes. It's available as oral tablets, 3 milligrams, 7, and 14 milligrams. There is some push and studies to show that oral version of semaglutide has shown to be efficacious for weight loss and obesity management. However, this is yet to get FDA approval. The next version of semaglutide is Ozempic, which is FDA-approved for glycemic control and to reduce the cardiac risk in type 2 diabetes. Third version is Vigovi, which is FDA-approved for obesity. The most recent of these medications is the tirzapatide group or Manjaro, which is approved for glycemic control in type 2 diabetes. The GLP agonists are sometimes associated with adverse effects, just like any other medication. The most common side effects that are noted to be with these medications include nausea, constipation, pancreatitis, gastroparesis, hypoglycemia, cholelithiasis, cholecystitis. It's also important to remember that these agents are contraindicated in a personal or family history of medullary thyroid cancer. Next up is phentermine and diethylpropion. These are both approved for short-term for weight loss, usually less than 12 weeks. These are appetite suppressants that can help with weight loss when combined with diet and exercise. These are both controlled medications and have a potential for abuse. In terms of phentermine, its mechanism of action is that it's a sympathomimetic amine. Side effects can include nervousness, increased heart rate, elevated blood pressure, dry mouth, and constipation, as well as dizziness. Mean weight change with phentermine per studies has been 6.1%. In terms of topiramate, it causes appetite suppression by several mechanisms. Side effects include brain fog, dizziness, fatigue, weight loss. It's important to remember it's contraindicated in pregnancy because of teratogenicity. The mean weight change for phentermine-topiramate combination was 10.9% in a 12-month study, which is substantive and I think should be considered when needed. Also important to remember that this is a class 4 controlled medication due to the phentermine component. Also important to remember that these could have drug interactions with alcohol, oral contraceptives, amitriptyline, anti-epileptic medications, MAO inhibitors, and potassium-sparing diuretics. Also for phentermine-topiramate, the FDA does include a warning and precaution for suicidal behavior and ideation and recommends to monitor patients for depression and suicidal thoughts and to stop the drug in case of symptom development. Regarding dosing of phentermine-topiramate, the initial dose is 3.7 mg for phentermine and 23 mg for topiramate administered as once daily for two weeks. This could be increased to 7.5 mg for phentermine and 46 mg for topiramate once daily from weeks 3 to 13. At that point, there is an assessment for weight loss. If greater than or equal to 3% of baseline weight loss has been met, then the recommendation is to continue at the same dose. If greater than or equal to 3% weight loss has not been achieved, the recommendation is to either discontinue gradually or to escalate dose. In terms of escalation, the next dosing is 11.25 mg and 69 mg once daily for two weeks. Thereafter, there is again a reassessment. If greater than 3% or more baseline weight loss has not been achieved, the dose could be titrated upwards. In terms of tapering, this medication could be switched to every other day dosing for at least one week and gradually go down from there. Next up is Orlistat, which is a different class of medications that has been approved. Meta-analysis of 52 randomized controlled trials showed that it's associated with a 3.1% greater weight loss than placebo. Studies in SMI patients have also demonstrated very modest weight loss for this medication. The mechanism of action of Orlistat is that it's an intestinal lipase inhibitor. The dosing is 125 mg with fat-containing meals three times a day, which can be somewhat of a limitation for some patients who have difficulty with medication compliance and remembering to take a medication three times a day. Several interactions are possible with Orlistat, including with levothyroxine, warfarin, and amiodarone and some other medications. In terms of side effects, the major side effects that are seen with Orlistat include oily fecal spotting, platelets with discharge, fecal urgency, steatorrhea, or increased defecation. It's also important to counsel patients about a balanced diet while on these medications and taking multivitamins like fats which contains fat-soluble vitamins like ADKE and beta carotene to avoid any deficiencies. Also regarding the GI side effects from early start, a low calorie diet with less than 30% calories from fat would lead to mitigation of some of those side effects. Next up is naltrexone bupropion, which is a second-line pharmacotherapy for weight loss given its lower efficacy compared with GLP-1 receptor agonists and phentermine topiramate. And the second reason would be that it's also required to be administered twice a day. So that is a limitation for some patients. However, this can be an effective intervention who also require concurrent mood stabilization and have familiarity with bupropion and naltrexone. The mean weight change with these medications was shown to be a weight loss of 6% over one year. RCT studies in schizophrenia patients did not demonstrate any weight changes or cardiometabolic benefits. In terms of other studies, systematic reviews have shown mixed evidence for antipsychotic associated weight gain. The mechanism of action for naltrexone bupropion is through POMC neuron stimulation and side effects do include nausea, constipation, headache, vomiting, and dizziness. Looking at this interesting image from a recent paper published in August in JAMA, this shows the titration schedule for this medication, wherein you start with one tablet, which is 8 milligram naltrexone and 90 milligram bupropion for one week. You start daily with one tablet a day, and then after one week, you increase to one tablet twice a day. Thereafter, after the second week, you increase to two tablets in the morning and one tablet at bedtime for one week, and subsequently increase to two tablets twice a day, totaling a dose of 32 milligram of naltrexone and 60 milligram of bupropion for a maximum dose. Also, important to remember that the FDA does include suicidal behavior and ideation under the warning and precautions for this medication and recommends to monitor patients for depression and suicidal thoughts and to stop the medication in case of symptom development. Also, the interactions do include with opioids, antipsychotics, SSRIs, TCAs, beta blockers, and several other medications. So, important to be cognizant of some of these medications if a patient is currently taking, if you're considering prescribing naltrexone bupropion. Next up is liraglutide. This is a drug that is used in the treatment of diabetes. Next up is liraglutide. In terms of research studies, data has shown that liraglutide has led to weight loss of 8% over one year's time span. This is, again, a GLP-1 receptor agonist. Obviously, the drug interactions could include with other GLP-1 agonists and other diabetes medications like insulin and sulfonylureas. Side effects include nausea, diarrhea, constipation, vomiting, headache, and dyspepsia. Research studies have demonstrated efficacy in patients with schizophrenia, schizoaffective disorder, or first-episode psychosis for weight loss. So, this is for liraglutide also. The FDA does have a package insert. There is a package insert for the FDA recommendation to monitor for suicidal behavior and ideation under warning and precautions. Other important fact to remember is increased heart rate can be a consideration and should be monitored with this medication. This is also listed under warning and precautions, as well as if patients complain of injection site problems, then injection sites can be rotated. Several other strategies can be tried to make the medication more tolerable, including water and dietary intake to limit constipation, as well as the last meal to be administered or taken more than two hours before bedtime to reduce heartburn. Next up is semaglutide. In terms of research studies, semaglutide has shown weight loss of about 15% over 16 months. This is, again, a GLP-1 receptor agonist, and side effects are very common with the same side effects noted with other GLP-1 agonists, including nausea, diarrhea, constipation, abdominal pain, headache, and fatigue. There is a small retrospective study on patients who failed metformin use in managing antipsychotic-associated induced weight gain, and that study showed results positive for semaglutide, and most patients on semaglutide had weight loss. Again, with the semaglutide, there is a FDA warning for suicidal behavior and ideation under warnings and precautions. FDA warning for suicidal behavior and ideation under warnings and precautions, and recommendation to monitor patients. Also important to, again, important to avoid use in patients who've had history of suicide attempts, and not to use in patients with personal family history of medullary thyroid carcinoma. Also important to monitor heart rate. Tizapatite, as I noted before, has shown to have the most kind of evidence for weight loss, including studies have demonstrated about 21% weight loss over 17 months. The mechanism of action for tizapatite is GLP-1 receptor agonist and GIP agonist. The side effects include nausea, diarrhea, vomiting, and dyspepsia. An important consideration for tizapatite would be to avoid use in patients with suicide attempts. Our most recent data on GLP-1 has failed to demonstrate any major correlation between suicidal attempts and GLP-1 agonist. In terms of psychiatric considerations in obesity pharmacotherapy, patient selection and tailoring treatment based on comorbidities is important. Also important to remember the potential impact of the medications on mood and anxiety, as well as addressing the weight gains associated with the medication. Also important to remember the potential impact of the medications on mood and anxiety, as well as addressing the weight gains associated with different psychiatric medications, for example, antipsychotics and mood stabilizers. Several times this comes up, and this is something you may be dealing with as well in your practice, is caring about compounded semaglutide alternatives. These become common in practice, especially around the country, due to shortage of anti-obesity medications, cost issues, as well as lack of insurance coverage of anti-obesity medications. Practitioners of patients have resorted sometimes to using compounded semaglutide alternatives. And these are some of the important things to remember when using or thinking about these alternatives. The FDA does warn about these alternatives, saying non-approved semaglutide products may use unverified salt formulations and lacking proven safety and efficacy. There's only two pharmaceutical companies authorized to produce weight loss FDA-approved medications, including semaglutide and terzapetide. And these, sorry, FDA-approved medications are approved only for Novo Nordisk and Elilelai. And these are the only options. Semaglutide, Bigovian, Azempic, and terzapetide, Monjaro, and Zepwong, these are the only FDA-approved medications that are approved. So compounded semaglutide alternatives can be an issue because it's unclear what salts are being used and their clarity. And there is a possibility that they may contain impurities or harmful additives that are also not reviewed by the FDA. Some of the versions could be counterfeit and could induce major safety concerns. And overall, the recommendation is to avoid using compounded alternatives to ensure safety and regulatory compliance. These are some of the major contraindications to anti-obesity medications. For example, medullary thyroid cancer or pregnancy for the GLP-1 agonist and terzapetide. For bupropion, the seizure disorder, bulimia, and myoinhibitor use are contraindications to use of bupropion. With naltrexone, the chronic use of opioids is a contraindication. Tantamine, the major contraindications include myoinhibitor use, substance misuse, and pregnancy. Topiramate and early start, the contraindications include pregnancy. Important to remember that none of the anti-obesity medications are approved in pregnancy. These are some of the FDA-approved medications for obesity. These include liraglutide, naltrexone, bupropion, early start, tantamine topiramate, and GLP-1 agonist. When used with lifestyle interventions, these medications result in an average of 5 to 15% weight loss. Setmelanotide emsevery is for use only in patients with obesity due to Bardet-Beetle syndrome or due to pro-opioid melanocortin convertase PCSK1 or leptin receptor deficiency, which is confirmed by genetic testing. These are some of the sites of action for these FDA-approved PCT medications in the brain, as well as the gut and intestines. This slide shows the efficacy compared to placebo for different medications. As we see, early start, 120 milligram three times a day led to weight loss of – average weight loss of minus 2.6 kilograms. Naltrexone-bupropion combo about 5 kilograms. Liraglutide slightly over 5 kilograms. And semaglutide and phentamine were noted to be more efficacious. Semaglutide noted to be most efficacious of this group comparison at 11.19 kilograms. And phentamine topiramate was followed. Semaglutide with an 8.8 kilogram weight loss. This slide shows the weight loss with subcutaneous semaglutide 2.4 milligram once weekly, over 68 weeks in adults with obesity or overweight. This is, again, percentage change in body weight with subcutaneous semaglutide in adults with overweight or obesity. Regarding terzapatite for the treatment of obesity, this shows a percentage change in body weight over 72 weeks. As we see, the 15 milligram dosing was the most effective and led to about 21 percent weight loss over 72 weeks. This slide shows the percentage change in body weight by a week for terzapatite. Again, the 15 milligram dosing showing to be most effective, but significant weight loss with the 5 and 10 milligrams as well. With the 5 milligram, there was 15 percent, and 10 milligram about 19.5 percent, and 15 milligram, there was 21 percent, versus placebo, which also incidentally showed some weight loss. This slide, an image from Chartour et al.'s paper, kind of compares the percentage weight loss or weight change on these different medications. These were the changes reported in the main phase 3 and extension trials of FDA-approved medications. The greatest change was in the weight loss medications. The gray color represents the placebo arms, and the red color represents the intervention arms. As we see in this, there is a certain gradient with the efficacies ranging from 5.8 all the way to 21 percent with terzapatite. As we see, as you move towards the right, terzapatite at different dosages, 5, 10, and 15, was the most efficacious of the lot, followed by semaglutide, which led to about 15 percent weight loss, and then followed by phentermine to pyramid extension, which led to about 10.5 percent weight loss. This can be used to calibrate the kind of weight loss your patients are needing based on their comorbidities and the efficacy. You can look at some of this comparison to decide how much weight loss you are aiming for and what is reasonable when starting a certain medication. This comparative analysis is helpful for setting patient expectations, as well as creating treatment planning which is suitable for your patients. Next up are dietary supplements. There is often a question that a patient might bring up in your clinical practice asking about a dietary supplement, whether they are taking green tea or some other over-the-counter medication supplement for weight loss. Overall, the recommendation is that we should caution our patients against the use of these weight loss supplements. They have no evidence for weight loss to support their efficacy, and the data is unsafeguarded. Green tea, carcinia, and conjugated linoleic acid have shown to be ineffective for weight loss for most studies. Some studies have discordant data, but the overwhelming evidence is not strong in favor of these medications. Randomized control trials have also shown that the HCG diet is also not more effective than placebo for weight loss. In terms of individualized selection, this slide is actually adapted for primary care use and says that this is a recommendation mostly for primary care settings. There is a recommendation to use Orlistat for depression and anxiety, Phentamine to use with caution, and Phentamine to Pyramid again to use with caution. I would add a caveat that psychiatric settings may involve the use of these supplements, I would add a caveat that psychiatric settings may involve a more nuanced background assessment for diagnosis and pathophysiology of psychiatric conditions and the medication mechanisms that your patients are currently taking, as well as the medication mechanisms of anti-obesity medications for you to decide on the most suitable option for your patient. So, this slide, while it's adapted for this presentation, is primarily for primary care and may not exactly fit the needs of your patients and may need to be customized. Your choices of medication selection need to be customized by efficacy, mechanisms, and side effects, as well as patient preference. This is, again, another algorithm from Chakthur et al. regarding weight-loss medication selection. In this algorithm for depression, Liraglutide, Naltrexone bupropion, Orlistat, and Phentamine to Pyramid have been highlighted. These are based on some of the studies that have been conducted in this group in depression. So, this is again an algorithm for depression and overall safety shown for some of these medications. So, these could be considered, but then again, I would again repeat that we should consider all options based on the patient comorbidities, and sometimes we need to discuss with other specialists about what is the best optimum option for your individual patient. There are some special considerations to remember when prescribing some of these medications. For example, Phentamine to Pyramid and Naltrexone bupropion should not be considered in patients if they have high blood pressure or tachycardia. For Liraglutide and Semaglutide, I pointed out that increased heart rate is considered under warning and precautions. So, patients prescribing the GLP-1 agonist should be monitored for increased heart rate. For Phentamine to Pyramid and Naltrexone bupropion and Liraglutide, the FDA does include warning and precaution label for suicidal behavior and ideation and recommends monitoring of patients. Arrhythmias are a contraindication for use of Phentamine, and tachycardia is also listed as an adverse effect for Naltrexone bupropion. Important to remember is that Lisdexamphetamine, also known as Vyvanse, is FDA approved for moderate and severe binge eating disorder. It can cause weight loss as a side effect, but it's not approved for weight loss or obesity treatment. Also, another important consideration to remember is after starting anti-obesity medications, responders are those who lose at least 5% of their baseline weight after three months of therapy, and the recommendation is generally to continue their treatment. Patients who have not lost 5% of their baseline weight after three months of therapy are considered non-responders and should be switched to another medication. A lot of talk was generated earlier this year and previous years based on some studies and some data wherein some side effects of some of the GLP-1 agonists were reported. So, there was a UTRA vigilance database that was created to look at the pharmacovigilance analysis of individual safety analysis of individual safety reports submitted to this database. A number of adverse effects were reported. Total adverse effects events that were reported were more than 31,000, out of which psychiatric side effects were about 372. Most important psychiatric events that were reported were depression, anxiety, and suicidal ideation, and that prompted a lot of the discussion whether GLP-1 agonists were safe in patients with psychiatric conditions or safe for patients in general. There were some deaths and adverse events reported with eight deaths were reported with liraglutide, one with semaglutide, and predominantly in men eight of nine due to completed suicide and depression. Psychiatric events overall, as you see from this database, are rare, 1.2%, but severe in some cases. There was a retrospective cohort study which found lower suicide risk among patients taking semaglutide compared to non-GLP-1 RA anti-obesity medications with a hazard ratio of 0.27. Let's talk a little bit more about the concern for the suicidality or suicidal thoughts or actions in patients with GLP-1 agonists. The FDA has been monitoring the condition and they released an update earlier this year. Their update states that preliminary evaluation does not suggest a causal link between these medications and suicidal thoughts or actions. FDA stated, we determined that the information in these reports did not demonstrate a clear relationship with the use of GLP-1 receptor agonists. Reviews of these clinical trials, including large outcome studies and observational studies, did not find an association between use of GLP-1 agonists and occurrence of suicidal thoughts or actions. Regardless, healthcare professionals should monitor and advise patients using these medications to monitor for worsening depression, suicidal thoughts, or unusual changes in mood or behavior. At this point, the FDA recommends monitoring for these medications and has not seen a causal link between GLP-1 agonists and suicidal thoughts and actions. This is another interesting slide based on some work by several researchers in the field comparing several of these medications and this meta-analysis comparing looking at different medications approved. So the relative potency of anti-obesity medications has been studied in meta-analysis and compared with placebo. As you see here in this slide, Arlestat was associated with about a 3% greater weight loss based on 52 randomized controlled trials out of about 17,000 patients. Phentamine to Pyramate was associated with about 8% greater weight loss. This is based on five RCTs with 3,400 plus participants. Naltrexone bupropion was associated with about 4.1% greater weight loss. Six RCTs, about 10,000 participants. And liraglutide associated with 4.7, semaglutide 11.4, and tirzapatide most with 12.4 based on six RCTs with about 2,000 participants. So you can categorize these studies alongside one of the previous slides we went through to look at some of the efficacy of these medications. There can also be a discussion with the patient's primary care doctor as well as looking at their other cardiometabolic states as well as the effects of some of these medications on cardiometabolic parameters while discussing and deciding and choosing a medication for these patients. Also important to remember that patients may have a preference for an oral agent. Some patients may have preference for or may not have a preference for TID dosing, for example with Orlistat. Some medications are not approved or recommended to be monitored with reproductive age women and none of these are recommended to be used in pregnancy. In terms of obesity treatment model, there is a multidisciplinary management of obesity model that is very popular in the obesity medicine sphere wherein a patient with obesity sees their primary care physician as well as interacts with several other specialists. This is applicable especially to a patient with psychiatric needs wherein they come to see you and they either have a nutritionist through a referral from a primary care physician and they may also be seeing an endocrinologist or an obesity medicine physician, but several specialists sometimes interact to provide the best care for obesity management. Multicomponent programs tailored to patients with SMI have shown significant weight loss and improvements in cardiometabolic health, therefore this model should be encouraged as much as possible. There was a study called an achieved trial wherein this was adapted for delivery by mental health center staff and demonstrated similar weight losses as well. So this model could also be used in mental health settings with some adaptations. Talking about considerations for medications as it applies to psychiatry, there are some medications that are noted to be more risky in terms of the weight gain spectrum. For example, SNRIs, TCAs, and SSRIs. They may increase appetite and trigger food cravings. We do know that there are some better alternatives available like propion, desfenilifaxine, vilazodone, vortioxetine, and floxetine. Some of these medications like floxetine, vilazodone, and vortioxetine, I've seen some patients gain some weight on these as well, however, they're less risky compared to some of the other medications who have a higher risk of weight gain. Similarly, talking about atypical antipsychotics, this could increase appetite and trigger binge eating. There could be better alternatives which are already present in the terms of xenomelane and traspium, which is one of the recently approved medications for patients. And the other options could be zeprasidone, lumatipirone. Luracidone and arepiprazole are other alternatives as well, though I've seen weight gains happen with patients who are taking luracidone as well as arepiprazole. Also important to remember, typically metformin has been added a lot late after an antipsychotic has started and patient has begun to gain weight. The current suggestions and recommendations from most data suggest to start metformin as soon as possible, especially if you're starting an antipsychotic. A lot of psychiatrists are beginning to start metformin in conjunction with an antipsychotic rather than waiting later on. So this preemptive strategy might mitigate weight gain with some of the atypicals. In terms of mood stabilizers and anticonvulsants, some of the agents like carbamazepine, lithium alphaate associated with higher weight gain risk, as we've seen, lamotrigine and topiramate are better alternatives. One question that often comes up between physicians as well as it's a dilemma for psychiatrists, I'm not certified in obesity management or I don't prescribe these medications. Should a psychiatrist really be prescribing anti-obesity medications? Important to remember that a lot of these medications that we prescribe for our patients, the psychotropics, many of them lead to weight gain. It's a common side effect, it's not rare. If unmanaged, it can lead to obesity as you may have noticed in several of your patients. Now in terms of our role in weight management, we can certainly consider anti-obesity medications to address weight gain. We do, however, need to look at individualized evaluation of benefits and risks for each individual patient and that assessment no one else can do that you can do because you know your patients the best. You can talk to your patients, look at their preferences, discuss their medical histories, talk to their primary care physicians, talk to other specialists that the patients are seeing and help patients make an informed decision if you're not making that decision yourself. However, there is some concern that if psychiatrists start prescribing some of these obesity medications, there could be an increased focus on weight gain and body weight and losing body weight, promoting disordered patients and disordered eating in some of our patients as we see. There is also this noted risk for increased risk of anorexia in vulnerable individuals and also psychological dependency in some of the controlled weight loss medications. However, one takeaway from this discussion would be that a careful patient-specific approach is crucial when prescribing medications to patients with psychiatric conditions. Important to remember that collaboration is a very significant part of obesity treatment. It's a shared responsibility. Psychiatrists do not have to manage this management alone. You can consult with PCPs, other specialists, and endocrinologists before prescribing weight loss medications. As we discussed before, a multidisciplinary approach provides the best care for patients with obesity. When needed, referrals to other specialists, including dietitians and exercise specialists, can be helpful. Involving therapists and support groups can be judicious and helpful in managing the psychological aspects of obesity. In terms of, you know, talking about medical legal considerations in prescribing anti-obesity medications, one of the considerations is that some anti-obesity medicines are not FDA-approved for weight gain in patients with psychiatric conditions and will likely be prescribed off-label. So if you were to prescribe such a medication, it does require a very clear documentation and an informed consent. The informed consent should discuss, as before, risks, benefits, and side effects of patients. It should discuss understanding and agreement, and that documentation should be thorough and appropriate. Also important that side effects, effectiveness, and psychiatric impact of these medications are monitored and treatment is adjusted as necessary. One of the things that comes up is scope of practice. So psychiatrists can prescribe obesity medications within their professional scope. However, sometimes additional training, like obesity medicine certification, can enhance competence. There is also importance of looking at the state laws and regulations as compliance with them is what defines scope of practice. In terms of collaboration and certification, as we discussed before, collaboration with other specialists can be helpful, and state laws and regulations should be looked at. Most states do allow psychiatrists to prescribe any FDA-approved medications with adequate training and clinical judgment for their use. Confirming scope of practice based on state-specific guidelines can be a judicious way to approach this prescribing dilemma. In summary, obesity is prevalent among patients with psychiatric disorders, and addressing it is critical to improving both physical and mental health outcomes. Several medications, including GLP-1 agonists, phentermine topiramate, naltrexone bupropion topiramate, metformin topiramate, sorry, that's a repetition, and Olistat can be considered. Certain medications offer synergistic benefits for mood and weight, like naltrexone bupropion. Tailoring medications based on patient diagnosis, risk factors, and patient preference is critical to a robust anti-obesity treatment, considering comorbid conditions is also significant in terms of creating a comprehensive treatment plan in discussion with other specialists. Investing in a motivational interviewing and five days model can help improve engagement and help patients attain a better weight loss outcome. Prescribing the least obesogenic medications can be helpful to prevent weight gain as well as limit and mitigate the cardiometabolic side effects that can be a concurrent effect of obesity. Combining medications with behavioral strategies, dietary modifications, and physical activity is beneficial. It's important to avoid missed opportunities by building better rapport with obese patients to enhance engagement. And as we discussed, working with other specialists can help provide the best optimum care to your patients who struggle with this debilitating chronic progressive condition. With that, I would like to end and take it over to Dr. Madan for any possible questions. Thank you so much. Thank you, Dr. Gupta. That was, oh my God, you covered a lot of ground. Thank you so much for walking us through demographics, through the different treatment approaches. And thank you for our audience who have been very engaging with a bunch of questions. So if you're ready or if you need a second to catch your breath, I can hang on. But I think we have around seven, eight minutes, so I'll try and go over some of those questions with you. So, so I think the first one talks about is metformin as effective when used with sodium valproate or lithium as it is with a use of antipsychotics? Dr. Madan, could you repeat the question again? Sorry. Yeah, no problem. So this question is about, is metformin as effective when it's used with sodium valproate or lithium as it is with the antipsychotics? Great question. As far as I know, I don't know any comparative analysis looking at mood stabilizers versus antipsychotics for metformin. That said, there is beneficial effects from metformin for weight gain, which is noted for several antipsychotics, whether that efficacy is comparative to antipsychotics is hard to determine because I am not aware of any data, but regardless, I would definitely recommend considering metformin if your patient is gaining weight on valproate or any other mood stabilizer. Yeah. And definitely metformin has been used with lithium, right? There's a bunch of anecdotal data on that. The next one about metformin talks about, is there any difference or can you comment on any difference between the efficacy between metformin and metformin extended release? Great question. So in terms of efficacy data, I'm not really aware of the efficacy data, but there is tolerability data. For example, patients with extended release, they have less GI side effects. Patients with immediate release have more upper GI side effects like nausea. In terms of efficacy, I have seen one thing though, that many patients would prefer a medication which is once a day versus twice a day. So just from a clinical standpoint, I do think that the extended release is a better bet given one, it has lower side effects for the GI system, less diarrhea, two, it's once a day dosing versus BID dosing. So personally, I prefer using the extended release version given that it's easier for the patients as well as it's kind of easier for patients to remember to take. And the GI side effects are primarily the major ones with metformin. So get more buy-in with the patients with the extended version. Yeah, no, I think that's a great point of clinical use. And if I could add, I think there is some literature in the diabetes world, right, about efficacy between the two being somewhat similar. I think there was a small study that talked about some decrease in LDL cholesterol with the extended collegiate, which wasn't, but again, how much do you take that into the clinical domain is questionable. I think you answered some of the questions about appropriate for psychiatrists to prescribe the anti-obesity medicines. I think you covered those at length. The next one is about olanzapine and semidorphin combination. So our audience asks, you know, this combination comes only with a maximum dose of 20 milligram to 10 milligram. Do you have a recommendation on how to manage someone who has been stable on olanzapine 30 milligrams? And when you're trying to switch to the combination, so they're already on 30, when you're switching, how do you work about that? So I think that's a gradual calibration that you can do. I've been there on 30, obviously, you want to be careful that you don't want to increase the risk of relapse. And you could consider adding 10 milligram to the 20, kind of keep the olanzapine kind of stable, because I think that would be a major risk for a patient who's stable on 30, if there is concern. You could also trial out the 20 first to see if the patient is responding okay. If there is slight concern, you could give it a week or five days and add the 10 back to kind of get the patient back to their therapeutic dose. But yes, that's a limitation with the dosing. Sounds good. The next one asks about any data availability on using the combination of naltrexone and bupropion for adults with ADHD. That's a great question. As far as I know, I'm not aware of any clinical data on adults with ADHD for that combination. Yeah, again, you know, not necessarily with a combination, right, obviously, bupropion has been used forever, but nothing that I'm aware of either. A couple of user, I guess, experiences, one, you know, one of the audience member talks about how they actually prescribe GLP-1 agonists almost daily as a psychiatrist and they talk about their favorite. And then another member talks about how obesity is a big problem in their patients who are on clozapine and most of them live in the adult foster homes. And they obviously don't have a choice when it comes to food selection that is served there and as it tends to be carb heavy and light on salad, very practical issue as well. The next question asks about, is there a preference regarding who should be prescribing metformin prophylactically? This is talking about inpatient versus outpatient. So many inpatient psychiatrists, they note, they say that it's the outpatient psychiatrist's role to handle this. And obviously, you know, there's a bit passing the buck on that. So any studies or any clinical pearls of wisdom on that? I'm not aware of any studies, but that's a great question. I do think that whosoever sees the patient should take that as an opportunity to prescribe then passing the buck on to the next person. If it is started in a timely way, it can, you know, lead to kind of mitigating weight gain. We do know that patients when started inpatient on medication can begin to gain weight. So the logistical reasoning says that this is something that should be addressed as soon as possible. And this is an intervention that should happen right away. There is also a possibility that sometimes these patients are discharged and it is a while before they actually see a psychiatrist in the outpatient community. And that period is a lost opportunity in terms of an intervention. That could have been done inpatient. So my suggestion is to do it as soon as possible, wherever possible. We have about one minute, so I'm going to rush through, maybe take two quick ones. One is on any data that talks about GLP-1s impacting absorption of medications, especially psychotropics. So again, I am assuming like with gastric slowing, is there any recommendation related to that? So gastric slowing is a known kind of side effect from the GLP-1 agonist. So I think you had to kind of look at the patient's medical state and the medications that you are prescribing. I don't know about any kind of research studies, but I think that's a, it's a parameter that needs to be assessed when prescribing our medications. So for example, pro-kinetic medications might be okay, but you know, other constipation causing medications, and then, you know, that can be augmented. And the last one is about insurance approvals. And I know that's probably a whole 30 minute talk in itself. Any quick pulls of wisdom there on what works, insurance, you know, still denies it. How do you go about it? So I think speaking to the primary care physicians and remembering the comorbidities and the criteria for approval are critical. Oftentimes a patient could be approved based on the comorbidities, but their BMI may not meet the 30 kilogram, 30 criteria. So I think remembering those and making a robust argument for your patient is critical. And sometimes soliciting PCP and specialist help is helpful to get that going as well. Thank you so much. I just want to applaud you for, you know, working so hard on, on this presentation. It's a lot of information and also want to thank you all for joining today's webinar. If you go to the next slide, please. Next slide. So two things, one, be sure to claim credit for your participation in the learning center. I think the, there was some instructions in the chat that were posted. I also wanted to share that at the upcoming APA annual meeting in Los Angeles, we have a four hour course on this talk as well. And we will be joined by the chief medical officer of the American board of obesity medicine. And she'll be doing a four hour course on that. So as you register, I know it's not online. The course is not online yet when you register. So it'll go online I'd say in a week or so. So please keep an eye for that. Also be sure to join our next emerging topic webinar, which is titled unseen consequences research linking childhood trauma and epigenetics. This is going to be by Dr. Stacey Drury, who's a professor and chair of psychiatry and psychiatrist in chief at the Boston children's hospital and famous for her work with the telomeric research and childhood trauma. And that's going to be on Wednesday, January 29th, 1 p.m. to 2.30 p.m. Eastern registration will be open soon for that. I just want to thank you all for your patience and hope this was worth your time. Thank you again, Dr. Gupta and have a wonderful holiday season. See you next time. Take care. Thank you, Dr. Madan. And thank you everyone.

obesity treatment

psychiatry

mental health

Dr. Vikas Gupta

5A framework

motivational interviewing

GLP-1 agonists

semaglutide

terzapatide

pharmacological treatments

weight management

multidisciplinary approach

metformin