PsychCase360: Balancing Psychiatric Stability and Cardiometabolic Health in Patients with Bipolar I Disorder

By: Joseph F. Goldberg, MD

Dr Goldberg takes viewers through two case profiles of patients with bipolar I disorder, including assessment, diagnosis, and treatment, with a focus on cardiometabolic safety.



Balancing Psychiatric Stability and Cardiometabolic Health in Patients With Bipolar I Disorder Video Transcript 

00:00 – Introduction 

Well, hello, everyone. Welcome to PsychCase360: Balancing Psychiatric Stability and Cardiometabolic Health in Patients With Bipolar I Disorder. I’m Dr. Joe Goldberg. I’m a clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York. Today I’m going to be walking us through a couple of clinical cases of individuals with bipolar disorder, really from the standpoint of assessment, diagnostics, differential diagnostics, and then therapeutics, with particular attention to cardiometabolic safety, a problem that is prevalent in patients with serious mental illnesses 

Such as bipolar disorder, often not talked about enough. So, our goal today is to really have a chance to fully appreciate the impact of cardiometabolic safety while treating patients with bipolar disorder.  

00:01:06 – Case 1: Vanessa 

So, let’s jump right in with our first case. Vanessa, a 26-year-old single personal trainer has a history of untreated depressive episodes that occurred during college. 

She’s brought by her mother to an outpatient crisis appointment after a recent marked change in her behavior and her mood. In particular, she exhibits an expansive, elevated, flirtatious affect, yet reports subjective feelings of depression. The history tells us she spends evening time awake, making workout videos that she’s convinced will make her rich and famous, and her grandiosity verges on delusional intensity. 

She reports having more thoughts and ideas that she can keep up with. She spends financially beyond her means on workout equipment, has ambitious plans to open a chain of fitness clubs. She has been neglectful of her personal hygiene, her eating, her self-care, she’s not paying her bills, has a basic disregard for needs and responsibilities. 

And when you talk with her, she has poor insight into the nature of her condition, but she’s open to the idea of treatments that might improve her mood, though she’s opposed to any medications that might cause weight gain. So, maybe you’ve met a Vanessa or two before. Let’s highlight some key features about Vanessa’s presentation. 

So, first her presentation, her history is certainly consistent with the diagnosis of bipolar I mania with these prior depressive episodes predating any manias from college. She certainly demonstrates the cardinal features of mania with expansive, elevated affect, grandiosity, sleeplessness, and energy. 

We’d like to be sure and find out as best we can whether or not this mania occurred despite treatments that she’s taking and represented a breaking through or whether she was just nonadherent to prior treatments. That’s an important point. We want to confirm that there’s no hint of a secondary mania in the picture. 

So, does she have a negative toxicology screen? Is she euthyroid? Are there any toxic metabolic factors to consider that might otherwise account for the presentation that we’re seeing? Given the severity of her presentation and her lack of responsiveness to treatments for depression before, we’d like to pick something that’s high efficacy in treating the current manic episode, but we also want to think about the proverbial risk-benefit analysis that goes into how we choose an efficacious treatment. 

We have many efficacious antimanic drugs, we’ll talk about those in just a moment—lithium, aripiprazole, other atypical antipsychotics—balanced against, well, her stated concerns about weight gain. So, the real goal is to effectively treat her mania while preventing or managing antipsychotic-associated weight gain. 

So, speaking of treatment options in the case of mania, we have many. Some are mood stabilizers. I never liked the term mood stabilizer. You know, it’s not a technical term. It’s almost more of a marketing colloquial term that we use to connote some intervention that can really achieve and sustain euthymia. 

4:10 – Treatment Considerations 

Some mood stabilizers mainly achieve and sustain euthymia by virtue of their antimanic properties. Lithium, divalproex, carbamazepine are probably the prime examples. Lamotrigine is not on our list because, while some people think of it as a mood stabilizer, it really lacks antimanic properties. 

Its forte is for the depressed side of the illness, especially for prevention of depression. Not so much for either treatment or prevention of mania. So, let’s say we have three antimanic mood stabilizers: lithium, divalproex, and carbamazepine. We can think about their pros and cons. Lithium certainly has efficacy in euphoric mania, tends to work especially well in a first or second or maybe third episode. 

So, that does capture Vanessa. Works especially well if there’s a positive family history of bipolar disorder, which we don’t know that much about. May work less well if there’s psychosis present. We’re not quite sure whether or not her grandiosity verges on the delusional or not. Works better when there aren’t really comorbidities present. 

So, there’s a number of things that might be attractive about lithium. On the downside, though, it’s not a fast-acting drug. It’s got a fairly slow onset. It’s probably better as a preventative than an acute drug and, well, it’s not weight neutral. Divalproex, similar to lithium and in some of the respects we talked about maybe a little faster acting in its onset with the rapid-loading strategy, but the weight gain is not so ideal as valproate, and in women of reproductive age,  

Some authorities would suggest that it’s not a great choice because of the risk of teratogenicity. Carbamazepine is fairly weight neutral, but it’s a strong metabolic inducer, and it also does have the same concerns about potential teratogenic effects in women of childbearing years. So, if we go through some of the atypical antipsychotics that have efficacy in mania and their pros and cons, such as aripiprazole, asenapine, risperidone, quetiapine, cariprazine, and so on, you know, all of these have antimanic efficacy. Some have maintenance efficacy as well, but some don’t. Some are a little better studied in mixed features or harder-to-treat forms of the illness than others are, but a lot of these compounds have weight gain and metabolic dysregulation. 

That’s a potential concern. So, we can go back and forth thinking about pros and cons. If we stop for a moment and focus just on efficacy: are all antimanic drugs created equal in terms of their magnitude of effect? I think it’s a tough question to answer because every individual is different, but if you think of this sort of in probabilistic terms, looking at population-based studies. 

6:44 – Choosing Among Agents in Bipolar Mania 

Graphic we have here talks about the magnitude of effect, the effect size across a wide range of agents. And what’s important to call out on this graphic is that the confidence intervals tend to overlap among many of these agents. So, if we look at this graphic, we could say, wow, haloperidol and risperidone and carbamazepine and olanzapine and cariprazine and aripiprazole are all among the highest efficacy drugs, but their confidence intervals overlap. 

So, it’s hard to declare differences from among them. At the top of this graphic, you see tamoxifen. Tamoxifen isn’t something we typically use to treat mania, but it was an investigational compound, really based on its mechanism of action as a protein kinase C inhibitor. And a study done at the NIMH some years ago showed it actually had a marked effect in that one study. We don’t rush out tomorrow and do it in a widespread fashion, but it was a proof-of-concept study. That’s why we see it there. And then toward the lower end of the graphic, we have agents where the confidence intervals will cross zero, and those would be nonsignificant differences compared to placebo. 

So, we have a lot of options to choose from among, and that kind of frees us up in some ways, in Vanessa’s case, to talk about pros and cons. It’s not like we have only one or two choices. So, we like to choose a fast-acting, broad spectrum, high-potency, second-generation antipsychotic. We might like to try to avert hospitalization as one of our goals. 

We’d like to potentially have something that could be in it for the long term as far as sustained remission if we’re successful in achieving initial remission. And certainly, good tolerability, both long-term and short-term.  

So, how do we position this to Vanessa? You know, there’s no crystal ball to guarantee what the outcome of any treatment is. 

We can say a few things, though. We can say it’s not going to take that long to know if something is going to work and if it’s going to have problems with tolerability. So, we might even say, yeah, we’ll know pretty soon, sooner than later, if something is working, and if it is, we can then make some decisions. 

If something is effective, but we decide the side effects are not worth it or not tolerable, we can always reevaluate that in fairly short order and move on. So, there’s a fluidity to how we think about treatment. We can also say, well, if something has a really wonderful effect, but there’s a side effect, nowadays we have ways to manage side effects. 

And that’s not unique in psychiatry. Every area of medicine has medicines that can cause side effects. And so, quite often we’re balancing risks and benefits. But if something has a particularly prominent benefit, and there’s a fairly easy strategy for side effects, for instance, tremor that can be treated with beta blockers or GI upset that could be treated with proton pump inhibitors. 

Often ways to manage side effects. So again, we want to convey to Vanessa, let’s get something that’s going to work. Let’s figure out if it’s well tolerated and then we can proceed from there. I also want to consider the notion of pairing a second-generation antipsychotic with an agent such as lithium. 

Why? A few reasons. One, well, you know, people talk about lithium as the gold standard drug. In some ways, it’s the old standard drug. It’s kind of the penicillin of antimanic drugs. It got there first. It’s got a kind of a narrow spectrum of activity. It doesn’t work great for a majority of people with bipolar disorder, but it does work particularly well in people like Vanessa, who have euphoric, expansive manias, who haven’t had multiple episodes go by in time, who don’t have mixed features, who don’t have mood-incongruent psychotic symptoms. 

And so we’re thinking both in terms of short term and long term. And in the back of our minds, we might be thinking if we could bring lithium into the picture, perhaps over the course of time, it might transition even to a monotherapy if it works. This sounds like Vanessa’s in her first manic episode, and I’ll tell patients, you’ll never again have your first manic episode. 

And your first episode may be especially lithium-responsive. So, it’s at least worth bringing it up. Now, onto this question of side effects and topics. So, the best way to not have side effects is to avoid things that have side effects, but, sadly, that’s a very short list. You know, even placebos have side effects. 

That’s called the nocebo effect. And it’s a real thing, especially in psychiatry. So, I think it’s important to let patients know that we as their clinicians are being watchful for the potential emergence of side effects and that we can do things about them. We can always stop a medicine, but we might be able to mitigate a side effect, even something like weight gain, which Vanessa tells us is a high concern for her. So, there’s a growing list of not just nonpharmacological diet and exercise and lifestyle interventions that can help modulate the risk for weight gain or metabolic dysregulation but pharmacological interventions as well. 

One that’s worth making note of is the combination of a kappa-opioid receptor antagonist called samidorphan. Paired with olanzapine, that’s a proprietary combination, which has been shown in clinical trials and FDA-approved, to mitigate or minimize the potential for the gaining of weight that might otherwise occur with olanzapine. 

So, this is not a weight loss intervention. This is something that can reduce the potential for the gaining of weight. And we have a graphic that displays—this is in patients with schizophrenia over the course of about a half a year. One can see on the top line that the magnitude of weight gain that occurs with just olanzapine all by itself.  

11:58 – Olanzapine/Samidorphan 24-Week Weight Gain Data  

On average, patients can gain about six and a half percent of their body weight over the course of half a year. And that’s reduced by about a third or more even. It’s down to about 4.2 % in patients for whom olanzapine is paired with this opioid receptor antagonist, samidorphan. Notice that the impact of the samidorphan seems to occur after about a month to a month and a half. 

So, it’s important to let patients know about time frames. If they start this combination strategy on day one and they say, “I’ve seen weight gain after a week,” which is possible, the time frame for really judging the plateauing effect of weight gain is more after about a month to a month and a half. Out to 24 weeks, we might see on average a weight gain of about three kilos with the combination compared to about five kilos with the olanzapine alone. 

And if we look at significant weight gain, that can be defined either as more than 7% of starting-out body weight or more than 10% of starting-out body weight. You can see the graphic on the right that the combination of olanzapine with samidorphan shows significantly less significant weight gain than is seen with olanzapine alone. 

So, this is one example of one component of an intervention to try to mitigate weight gain in a patient where we might be thinking about a very high-potency antimanic regimen based on their severity.  

13:29 – Case 2: James 

Let’s move on to a second case now: James, a 47-year-old African American male. Divorced, professional, initially presents with a hospitalized manic episode in college, followed by three subsequent manic episodes, despite taking lithium and/or divalproex in combination with a second-generation antipsychotic, aripiprazole on one occasion, or quetiapine on another. 

So, a lot more pharmacological history for James than was the case with Vanessa. He had a prior response to olanzapine, but he stopped after about a 15-pound weight gain. That’s important, we’ll come back to it. He’s now brought to the emergency department by his brother. He’s irritable, he’s sleepless, he’s provocative and argumentative with his co-workers. 

He’s spending lots of money at strip clubs. He’s claiming he’s had ideas to invent new phone apps he’s convinced that will revolutionize the tech industry and make him rich. So, he’s admitted to the hospital, and the decision is made to begin him on olanzapine. Per the package insert, one might start at 15 mg and go up rather quicthat hkly to 20 mg/day. 

Combination with divalproex 1500 mg/day that gives him a serum valproic acid level in the therapeutic range, right at the sweet spot, about 84 mcg/dL. And as one might expect and hope, with this regimen, he’s stabilized fairly quickly, and then he transitions to a step-down program. 

James has a personal history of hypertension. He’s on losartan. He also has hypercholesterolemia. He’s on a statin, simvastatin, and there’s a family history of heart disease, in fact, a heart attack at the fairly young age of 52, in his father. And he’s got familial hypercholesterolemia.  

So, let’s talk about some of the key features for James. 

So, his presentation certainly is consistent with bipolar I mania. And, similar to Vanessa, we want to be sure that this is an episode that is not merely an artifact of nonadherence to prior treatments. It’s always a conundrum, you know, was someone on an efficacious treatment, did they just stop taking, in which case adherence becomes the variable, or was it true lack of efficacy? 

In James’ case, we have a history pointing to multiple treatments he’s taken that were not efficacious. As was the case with Vanessa, we want to be sure this is not a secondary mania, a negative toxicology screen. If there are substances in the picture, we’d like to try to clarify chronology. Did the mania precede any substances? And the substance use, if it occurs, came as a consequence of the mania as opposed to a substance-induced mania. 

Here we have a very severe presentation of psychotic mania that hasn’t gotten better with prior treatment. So, even more so perhaps than was the case with Vanessa, we really want to make sure that we’re picking high efficacy treatments that have a very high likelihood of resolving this episode quickly, safely, and effectively. But also, similar to Vanessa, we’re doing our risk-benefit analysis. 

Now, it’s a little bit different for James. When prior things haven’t worked, what do we think about? I mean, what are big gun options in hard-to treat mania? Olanzapine, clozapine, ECT are all things we might want to consider, especially for swift intervention and also for thinking about relapse prevention. 

ECT is a little bit harder for relapse prevention. It’ll knock down a mania, but then we still need some intervention to prevent the next phase of illness from occurring. And then again, as was the case with Vanessa, how do we balance the potential for weight gain against the high severity of James’ condition, particularly given his personal and family history of cardiovascular metabolic liability? 

So, let’s dig a little bit deeper. We know that James has some cardiovascular risk factors and a family history of cardiovascular disease at a fairly young age. We can quantify James’ cardiovascular risk in a little more detail. In the old days, we calculated a Framingham Risk Score for people like James. 

17:23 – Pooled Cohort Risk Equation for Cv Risk 

And nowadays, we have a snazzier incarnation of the same concept to predict the risk of a heart attack, something called the pooled cohort risk equation, and that’s depicted for you on the slide. It’s easily downloaded on the web. This was developed by the American Academy of Cardiology. It takes into account some specific factors, some demographics, age, sex, race, blood pressure, treatment for blood pressure, diabetes status, smoking status, and this will calculate for you someone’s 10-year risk for atherosclerotic cardiovascular disease. 

And we like to see this number under 7.5. Why is that a magic number? With the best of risk factors, that’s about what the 10-year risk for someone that James’s age might be for a cardiovascular event. So, James comes out with a 10-year risk of 9.4%. That is higher than the 7.5% that would make us feel much more confident, which is to say that, you know, James’ risk for cardiovascular disease is not trivial. 

At the same time, his functioning is impaired. His symptoms are prominent. He’s in the hospital. So, what do you want to do if we construe James not just as a manic episode but as a severe psychotic manic episode that’s seriously jeopardizing his fundamental wellbeing and hasn’t gotten better with other things? 

So, I showed you a slide a bit earlier saying that many antimanic drugs have comparable efficacy. I lied to you because, while that’s true on an overall basis, that doesn’t take into account somebody who’s been unresponsive to multiple other treatments. And in this next graphic, we have a fairly nice summary of some data with olanzapine, 

Specifically in the setting of patients who did not get better with multiple previous, otherwise effective antimanic drugs, including multiple atypical antipsychotics. So, this is important information, and we often don’t take into account this variable of previous treatment responsivity—or lack thereof. 

19:04 – Olanzapine Treatment-Resistant Mania Data 

We sometimes just sort of randomly try this, try that, like throwing darts at the target, rather than saying, what’s been studied and shown to work when other things don’t? And as you can see on this graphic in this study of patients for whom multiple other antimanic drugs didn’t work, we see significant reductions down the line in mania symptoms, depression symptoms, global improvement, positive symptoms, negative symptoms. So, nothing’s perfect. It’s not the be all and end all. But that risk-benefit analysis has to take into account the significance of James’ cardiovascular disease and the significance of his hard-to-treat mania.  

20:08 – Discontinuing Olanzapine Before 6 Months 

How long do you stay on an atypical antipsychotic if you’re on one and you start getting better? 

It’s an important question. It’s empirically answerable by randomized discontinuation trials. Here’s one which compared manic patients who were on olanzapine or risperidone plus an antimanic mood stabilizer, lithium or valproate, and asked how long should you stay on it? If you’re randomized to the combo, or if you just stay on lithium or valproate alone, and it turned out, the highest risk for relapse was the first half year, the first 24 weeks. 

If someone jettisoned your atypical antipsychotic, you had a much greater likelihood of relapsing in the first six months than if you were taking the combination. Whereas after six months, the lines kind of got a little more even. The risk for metabolic adversity continued, but the chance of relapse prevention started to become more similar. 

So, from this important randomized discontinuation study, we might say to someone, let’s get you better and keep you well for six months. And after six months, we can reevaluate things and decide if it is or isn’t worth retaining the atypical antipsychotic, particularly, as I said, if this is a severe presentation, if other things haven’t worked, and if we have some weight gain mitigation strategies. 

We have to think about mitigation strategies because the potential for weight gain with olanzapine is not transient. Here’s a study that was done some years ago, which showed that the risk for plateauing eventually with weight gain happens after about 39 weeks. No patient wants to be told that. When will this weight gain stop? 

21:26 – Olanzapine Weight Gain Plateau Data 

Almost a year from now is no way to really engage someone. So, we really want to make it clear on the front end. We want to intervene and do things to minimize the risk. One thing we can do to anticipate risk is to look at the amount of weight gain, if it occurs, early on.  

Here’s a handy little algorithm that showed empirically, some years ago, how much weight gain, if any, occurs in the first few weeks. 

And it turns out if you gain more than about four to five pounds in the first three weeks, the probability of seeing significant weight gain, right (that can mean more than 7% of your initial body weight or more than five kilos from your starting-out weight) is substantially higher than if you don’t gain four to five pounds in the first two to three weeks.  

So, this metric is pretty useful because in the first two to three weeks, you’re going to know if the treatment you’re giving is working, and if it’s not, move on to something else. Maybe ECT, maybe who knows what? But if it is working, let’s get you out of the woods, get things more stable. 

And then let’s talk about mitigation strategies and then try to keep you well for at least six months, at which point we could jettison what might otherwise be a more high liability drug that could be life saving.  

So, what are some other mitigation strategies? Metformin is widely talked about as a useful strategy to either prevent or reverse weight gain. 

22:49 – Metformin with Antipsychotics 

It does speak to the mechanism by which weight gain occurs with atypical antipsychotics, at least one of the mechanisms. Many atypical antipsychotics cause weight gain because they increase appetite. They can stimulate 5-HT2C receptors, which in turn can stimulate the satiety center in the brain, and so, you don’t feel full after you eat. 

 They can also disrupt signaling from brain-gut hormones, like adiponectin and leptin and ghrelin, which are supposed to tell you, “Stop eating, we’re done, we’re full.” Disruption of that signaling pathway can be a potential complication.  

And last but not least, and arguably the biggest complication, is insulin resistance. 

Some, not all, but some atypical antipsychotics cause insulin resistance. That means you can’t use sugar. You can’t burn it efficiently. So, remember insulin is like a chaperone. It pulls glucose out of your bloodstream and into your organs. People with insulin resistance can’t effectively use glucose. It stays in their bloodstream. 

So, insulin is not able to facilitate its transport into organs. Sugar stays in your bloodstream, and then it finds its way to your liver. And in your liver, it decides to convert itself to fatty acids and glycerol and make cholesterol and foie gras out of your liver. And then it’s exported out to the periphery, and you get adipose tissue. 

So, this is really the nasty process by which weight gain can occur from insulin resistance. Metformin helps to overcome insulin resistance. So, in that sense, it’s a really good idea. It’s not a random idea. It doesn’t specifically suppress appetite, but it can help with insulin resistance. The bad news is it doesn’t translate to a necessarily dramatic weight-loss effect. 

This meta-analysis said about a three and a third kilogram weight decrease over short term. So, that’s certainly better than nothing, but it ain’t astounding. Another strategy is topiramate. So, this is an off-label use. Topiramate is a migraine drug. It’s an anticonvulsant drug. At one time, it was looked at for potential antimanic effects. 

It really didn’t have any, but boy, it caused weight loss in people, mostly through appetite suppression. Not so clearly through insulin resistance. And here, the number is a little bit better. So, an average weight decrease of about five kilos, it’s a little more than 10 pounds, about 12 pounds, over the course of time in clinical trials to reverse second-generation antipsychotic weight gain. 

25:04 – Topiramate Weight Mitigation Data 

Your wheels are turning now, you’re thinking, what would happen if I was going to use olanzapine for James, pair it with samidorphan to mitigate the potential gaining of further weight, and then throw on some metformin and some topiramate, da da da da da da? This sounds really good and very scientific, and it actually makes a lot of sense. 

The thing is, I’ve got to say to James, you know, the gravity of your illness really requires that we take a very serious approach and not a random approach. We don’t want you in and out and in and out and into the hospital, but we have things that we can do. Here’s three examples. Here’s the fourth example: the breakthrough pharmacology, so called glucagon-like peptide 1 agonists, or GLP-1 agonists. 

25:52 – GLP-1 Receptor Agonists 

So, these molecules have been widely celebrated in the popular media because of their profound potential for weight loss. They’re kind of like metformin on steroids in that they really are insulin mimetics. They make insulin do more things to help overcome insulin resistance in the periphery. And you know, that’s the whole mechanism of type 2 diabetes, which can happen with some atypical antipsychotics. 

Don’t confuse that with type 1 diabetes, where your pancreas doesn’t make insulin, that’s not an issue with atypical antipsychotics. It’s type 2 diabetes risk or peripheral insulin resistance. So, the very compelling thing about GLP-1 agonists, it’s as if to say they were made for overcoming weight gain caused by atypical antipsychotics because their mechanism largely is as an insulin mimetic to help overcome insulin resistance in the periphery, to reduce glucagon release that increases blood sugar. 

There’s also some degree of appetite suppression and a pro satiety effect with these drugs. They’ve just begun to get looked at to treat iatrogenic weight gain. They’re popularly used, well, certainly to treat diabetes, and then at least two compounds, there’s tirzepatide and semaglutide in proprietary forms, are also FDA-approved for just weight loss. 

If your body mass index is over 27, with at least one health-related consequence like hypertension or hyperlipidemia or if your BMI is over 30. But what if you’re taking olanzapine or clozapine or any of the atypicals and you’ve had significant weight gain? Does this theory hold that you can overcome insulin resistance with a GLP-1 agonist? 

27:35 – Liraglutide for Antipsychotic-Assoc. Weight Gain 

The preliminary data look pretty favorable. Liraglutide, that’s another GLP-1 agonist. It’s a daily injection. These medicines don’t have such great bioavailability when given orally. So, this once-daily injection had a significant reduction over the course of 16 weeks, about a 12-, 13- pound weight loss with reduction in a lot of the parameters that we care about. 

Total cholesterol came down nearly 20 points, bad cholesterol came down 15 points, fasting sugar went down, blood pressure got better, so, you know, semaglutide and other of these  GLP-1 agonists even recently received its FDA indication to reduce the risk for heart disease. So, wow, there’s a lot of reasons to be very optimistic about these drugs. 

The two that we think of mostly in nondiabetic patients, a formulation of semaglutide and a formulation of tirzepatide. And both of these have also been looked at, at least preliminarily, to counteract iatrogenic weight gain. 

28:20 – GLP-1 RA in Non-Diabetic Obese Patients 

I mentioned just a moment ago, there was the recent FDA relabeling of semaglutide to reduce the risk of cardiovascular disease. There was a nice meta-analysis demonstrated here that shows a 14% relative risk reduction in major adverse cardiovascular events. 

This is in diabetic patients. But, so, when someone is not simply looking to lose weight, but maybe hyperglycemic and has peripheral insulin resistance, and maybe some of the cardiovascular sequelae, and you do your pooled cohort risk equation like you did for James, and it’s meaningfully over 7.5,  

We finally have some strategies that we can implement to make life-saving treatments more efficacious. Clozapine, for example, is the only psychiatric drug that’s label says it can reduce the risk of suicide completions in schizophrenia patients. As a psychiatrist, I would hate to withhold a medicine like that from a patient who could benefit from it because I’d feel helpless about the metabolic liability. Well, the GLP-1 agonists provide us with a whole new way of thinking about this risk-benefit analysis. 

All right, so we’ve covered a lot of ground. Let’s summarize some key points. First, bipolar I disorder presents complex challenges for managing psychiatric stability while minimizing cardiometabolic risks. Effective treatments really involve a nuanced understanding of each patient’s history, past treatment response, current health status, a very integrative approach. 

29:48 – Summary and Conclusions  

We have many pharmacological options that exist now, all of which have their unique pros and cons with regards to efficacy, speed of onset, side effects such as weight gain, patient preference. Shared decision making really invites, if not demands, a shared dialogue about what the treatment goals really are. 

In Vanessa’s case, we saw the importance of addressing the manic symptoms without exacerbating weight gain or metabolic concerns. And in James’ scenario, we saw the difficulty of trying to treat a hard-to-treat recurrent form of bipolar disorder that prior treatments were not effective for, balanced against non-trivial cardiometabolic health concerns. 

So, what can we take away from these presentations? Well, again, we want to think about high efficacy treatments, the fact that side effects may be an inevitability with almost anything we prescribe. But to the extent that we have strategies to manage side effects, we’re much more equipped to engage in this shared decision-making process. 

In early presentation, first-episode patients in particular, think about the role of lithium. You know, atypical antipsychotics are in many ways cornerstone treatments for bipolar mania. Some even treat bipolar depression, but let’s not forget about the role of mood stabilizing compounds, especially for long-term care. 

If a patient finds themselves in that enviable minority of patients with bipolar disorder that are responsive to lithium, we’d like to know that. We want to think about the growing array of options that we can use to treat adverse effects around weight gain or metabolic dysregulation. We’ve talked about ways to try to manage insulin resistance from metformin to the emerging database with GLP-1 agonists. More and more we’ll hear about that in times ahead. 

A great need for ongoing research to explore these integrative approaches, to give us more information about using compounds such as GLP-1 agonists specifically to counter iatrogenic weight gain caused by psychotropic medications. 

And lastly, really, mental health providers, prescribers of all stripes in mental health really want to be mindful of this holistic approach to treating the patient, not skimping on high efficacy treatment and being mindful and aware of the potential ways to mitigate side effects and balance efficacy with tolerability. 

Let’s stop here for now. I hope this was a helpful overview for you. I want to thank you for taking the time to join us today and hope to see you again soon.