Bipolar Disorder

Edward Kilbane, MD, addresses diagnosis of bipolar disorders and details the current treatment landscape.

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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab and psychiatry.

Glen Stevens, DO, PhD: Bipolar disorder affects approximately six million Americans, often first striking in the prime of their lives, affecting mood, energy, and activity levels. Accurate diagnosis is paramount in distinguishing bipolar disorder from other mood disorders, requiring a nuanced understanding of its unique symptoms and patterns.

In today's episode of Neuro Pathways, we're sharing practical insights for accurate and timely diagnosis and management of bipolar disorder. I'm your host, Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. And I'm very pleased to be joined by Dr. Ed Kilbane. Dr. Kilbane is a psychiatrist and the medical director of Emergency Psychiatry in Cleveland Clinic's Neurological Institute. Ed, welcome to Neuro Pathways.

Edward Kilbane, MD: Thanks, Glen.

Glen Stevens, DO, PhD: So Ed, to start, tell us a little bit about yourself, how you made your way to the Cleveland Clinic and what you do on a day-to-day basis.

Edward Kilbane, MD: Sure. So as you said, I am a psychiatrist. I am originally from Cleveland, but I worked different places over the years. Came back to Cleveland about 10 years ago, worked at University Hospitals for a couple of years and then at St. Vincent's and then came to the Clinic in January 2024. Most of my background is in psychiatric issues of cancer patients and emergency psychiatry. And as you said, I've been the medical director of Emergency Psychiatry for the past nine months or so.

Glen Stevens, DO, PhD: So let's start broad for today's conversation with what is bipolar disorder? Take us through the various types and how we figure it out.

Edward Kilbane, MD: Sure. So I think, first and foremost, bipolar disorder is a mood disorder. And so we conceptualize the different categories of psychiatric diagnostic classifications. There's a whole group of mood disorders and so bipolar disorder does fall under that heading.

According to our most recent Diagnostic and Statistical Manual 5, there are a few types of bipolar disorder, the most common being bipolar I disorder and bipolar II disorder. Much more rare, you see something called cyclothymia or also kind of bipolar disorder with just mania, which is quite rare. But, clinically, what we see, most of the time, is either bipolar I disorder or bipolar II disorder.

The big differentiating factor between those two is the presence of a manic episode versus a hypomanic episode. And so bipolar disorder has two poles of mood, depression and mania or hypomania, and so patients will experience those episodes of depression and then a different episode mania. And interestingly, most patients with bipolar disorder experience most of their mood issues as depressive issues. So they have many more depressive episodes than they do manic episodes throughout their lifetime.

Glen Stevens, DO, PhD: Well, I think TV always gives a skewed view of bipolar disorder in movies, right?

Edward Kilbane, MD: It does. I mean, one, that bipolar disorder is characterized mostly by mania, which is not the case. And also that, oftentimes, manic episodes are kind of euphoric and somewhat enjoyable, when the reality is that they can quickly become difficult to manage. A lot of irritability and kind of a scary experience to have.

Glen Stevens, DO, PhD: So define for us the difference between mania and hypomania.

Edward Kilbane, MD: So I mean, it's kind of in the words, hypo meaning below or underneath. So it's kind of just a slightly different version than mania, but mania itself is defined as mood symptoms that last for at least a week, most days of a week. And these symptoms can include an alteration in mood, usually euphoric or irritable or labile, kind of rapidly shifting mood, a decrease in a need for sleep, an increase in speech production or inability to stop speaking, an increase in motor activity, increase in different goal-directed activity, and sometimes an increase in risk-taking behaviors. Also, very rapid thoughts. 

So that constellation of symptoms happens in mania and it has to impact daily functioning, whether that be in work or in family relationships or other social functioning. But, really, the differentiator is that a manic episode will have these symptoms and those symptoms will interfere with a person's ability to function in day-to-day life. 

The other differentiating factor is psychosis. So psychosis, psychotic symptoms can happen with either a depressive episode or a manic episode in bipolar disorder. You don't get psychotic symptoms in a hypomanic episode. So if someone has manic symptoms and they also have the addition of psychotic symptoms, like hallucinations or paranoia, then that, by definition, defaults to a manic episode.

Glen Stevens, DO, PhD: And genetic risk? If my parents have it, what's ...

Edward Kilbane, MD: So there is, like many mood disorders, including major depressive disorder, there is heritability. We don't understand it that well. It seems to be about the same for bipolar I and II. There's a slight difference in the incidence of those, but genetically seemed to be linked as well.

Glen Stevens, DO, PhD: Male versus female?

Edward Kilbane, MD: It's about the same for sex differences.

Glen Stevens, DO, PhD: And typical age of diagnosis? May not be presentation, but age of diagnosis? And I guess that's a question you could answer as in how long does it take from presentation until people get diagnosed and what's the average age?

Edward Kilbane, MD: Great question. So certainly does tend to present a little bit earlier, twenties and thirties, often. Probably a little bit later than the onset of psychotic symptoms in schizophrenia, that's usually late teens to early twenties. Bipolar disorder will usually manifest sometime in early adulthood. One of the issues with diagnosis is that because the mood episodes and bipolar disorder are often depressive episodes, someone might actually present with a history of depressive symptoms, not necessarily any history of manic symptoms because they haven't had that component of the illness yet. And so they would be diagnosed, misdiagnosed, unfortunately, as major depressive disorder. That's not the clinician's fault, that's not the patient's fault. It's just that the patient has not yet experienced the manic side of bipolar disorder.

Glen Stevens, DO, PhD: So how do you figure it out, then, if they are just having major depression or do they have bipolar, if they've not yet had a manic event? I guess maybe you can't.

Edward Kilbane, MD: That's a great question. It's difficult to do, for sure. I mean, certainly, we talked about the genetic risk. So if there is a strong family history of bipolar disorder, especially in first-degree relatives, then you might see a patient presenting to you with depressive symptoms as maybe more likely, potentially, having bipolar disorder, given the family history. 

They might also, just because they haven't had a diagnosed manic episode in the past, they might've had behaviors or symptoms consistent with that in the past. So really getting a detailed history to understand, historically, have there been periods of decreased need for sleep, elevated energy, increased speech production, increased thought speed? Those things might clue you into the fact that this person actually has experienced some mania before, it just hadn't been captured or diagnosed.

Glen Stevens, DO, PhD: How young can you develop bipolar?

Edward Kilbane, MD: I mean, in teenage years. Certainly, people can present that early.

Glen Stevens, DO, PhD: And is there an age you go past where you should really be thinking about something else?

Edward Kilbane, MD: You don't tend to see it much later in age. Again, I think when we see bipolar disorder diagnosed in the fifties, sixties, seventies, it's usually that it's been present for quite a while and just hadn't been appropriately diagnosed or captured.

Glen Stevens, DO, PhD: So I assume with a lot of depressive symptoms going on, which is probably the bigger trigger, there's probably an increased suicide risk. What's that look like? And is it different between the types? I would assume ...

Edward Kilbane, MD: Yeah, so certainly bipolar I disorder with the mania would be the higher suicide risk. Actually, amongst mood disorders, bipolar disorder has the highest suicide risk. And part of that is that they do spend so much of their mood episodes depressed and suicidal ideation certainly being a prominent symptom in depression.

Glen Stevens, DO, PhD: And I assume that's how some people get initially diagnosed, right, a suicide attempt or pseudo attempt?

Edward Kilbane, MD: Yeah, or someone presents as so depressed and they maybe gets admitted for that and then the history is teased out a bit more. Or maybe their symptoms start to fluctuate when they're followed as an outpatient then. And so I think one of the important things for providers, psychiatrists or otherwise, is to be mindful that we might diagnose someone with major depressive disorder and that we just need to be open that if their symptoms change, if they're presenting down the road with a different cluster of symptoms, to be open to the idea that this might actually be a bipolar disorder, and then to adjust our diagnosis accordingly.

Glen Stevens, DO, PhD: So I'm following a patient, their mood seems a little down, that type of thing. What do I look for them to actually be bipolar? I guess they would have some type of manic or hypomanic event to be that simple, would it?

Edward Kilbane, MD: Yeah, I mean, in some ways it really is. It's trying to understand do they have an episode where, for hypomania it's at least four days for mania, it's at least a week. Do they have that stretch of consecutive days where they're having symptoms that are more consistent with a manic episode?

Glen Stevens, DO, PhD: And substance abuse, I imagine, unfortunately, it's probably too high, people self-medicating on both ends?

Edward Kilbane, MD: Yeah, it's a really difficult thing to tease apart because, oftentimes, part of bipolar disorder is, as you just said, trying to self-medicate. If someone's depressed, maybe they want to use stimulants to try to feel more energy and more engaged. If someone's manic, maybe they're drinking alcohol or using a lot of cannabis to try to help them slow down and maybe get some sleep. And they might be doing this without even knowing that they're kind of self-medicating. 

But there's a flip side to it, too, which is that some of the symptoms of bipolar disorder, specifically mania, are kind of impulsivity and increased risk-taking behavior and drug use certainly falls into that category. So sometimes, to what extent is the individual trying to medicate their symptoms, as opposed to acting in a way because they're decompensated? And then, unfortunately, the end result is that most substances really do not have good long-term impacts on mood. And so it really just exacerbates the issue overall.

Glen Stevens, DO, PhD: So as a brain tumor guy, I'm a little concerned about a patient maybe having bipolar disorder, and of course it's out of my comfort area, so I'm going to send them right over to see you. You diagnose bipolar disorder. How do you treat them? What's the plan?

Edward Kilbane, MD: So I think, most importantly, is actually arriving at an accurate diagnosis because that's going to drive what the associated treatment is. So really trying to get a history and understand is this truly a bipolar disorder? And then if it is bipolar disorder, is it bipolar I versus bipolar II? And is there even a subcategory, say, of bipolar I? Are they having psychotic features? Are they, what we call, rapid cycling? Meaning they're having at least four episodes, mood episodes a year? Are they catatonic? So really understanding the nuances of the diagnosis will help guide some of the pharmacological interventions. 

But once a diagnosis of bipolar disorder is arrived at, we really have some pretty good guidelines as to what pharmacological agents we should use. And the mainstay of treatment would be mood stabilizers. You would think that an antidepressant would be a good idea, and someone who has a mood disorder, and a lot of their episodes are depressive episodes. But the evidence isn't actually really that great for antidepressants in bipolar disorder. And there's actually some concern that the serotonergic activity of a lot of our antidepressants can actually push someone into a manic episode. There's some pretty decent evidence for that. So a lot of the mood stabilizers we used actually are FDA approved, not just for bipolar disorder, but bipolar disorder in a depressed episode, they have some inherent kind of antidepressant effects to them.

Glen Stevens, DO, PhD: What about psychotherapy?

Edward Kilbane, MD: So certainly psychotherapy can be very effective, and probably the most standard psychotherapy that we use in mood disorders is cognitive behavioral therapy. That's a type of therapy that's been around for quite a long time, has a lot of evidence to support it in mood disorders. Kind of looks at how is someone actually cognitively looking at a situation. Is it accurate? If it's not accurate, how do they change the way they think about it, so they have an associated mood that is appropriate? And that certainly can be used in the depressive phases of bipolar disorder, maybe a little bit harder in the manic phases, where someone's ability to think is not as coherent as it might normally be. 

There's family-focused therapy. Has been quite useful over the past couple decades, and that really aims at two things or three things. One is how does the family of a patient, specifically if the patient lives with the family, how do they help manage this on a day-to-day basis? How do they help ensure things like good sleep hygiene and kind of normal routines? Another thing is that family members or those close to a patient are, oftentimes, able to pick up on some subtle signs or symptoms of mania. So maybe see some of the decreased sleep pattern happening a couple of weeks in advance or see some increase in impulsivity or certain behaviors that might clue them in.

And a third thing is that there's some pretty good evidence that in family structures, there's a concept called expressed emotion, where if family members express a certain degree of hostility, criticism or over-involvement, that patients actually do a lot worse and they get hospitalized more often. Part of that is that when people are telling you to take your medications all the time and do what you're supposed to do, one of the normal human reactions is to do the opposite. And so really helping families understand that they can approach these problems, but in a way that doesn't actually make the person worse.

Glen Stevens, DO, PhD: And I assume if they have substance abuse, that has to be worked on as well, right?

Edward Kilbane, MD: Absolutely. Absolutely. And a lot of, certainly, inpatient psychiatric units and outpatient psychiatric providers can do that to a certain extent. There are quite a few dual diagnosis programs, both outpatient and inpatient, where really the focus is equally on the psychiatric issue, as well as the substance-use disorder issue.

Glen Stevens, DO, PhD: And what's the buy-in with cognitive behavioral therapy for patients or some type of psychotherapy? 10% of them will buy into it? 50%, 70? Do we have any knowledge?

Edward Kilbane, MD: Yeah, that's a great question. I actually don't know the percentage just off the top of my head, but I think informing patients that there are tools to address their symptoms and pharmacological tools are one of them. In bipolar disorder, there's several – psychotherapy, pharmacologically, also lifestyle management. Again, making sure that you have a consistent routine, a consistent sleep, things like that. So I think, sometimes, when you present a patient with the idea that there are multiple ways to address this and it puts them in control, there seems to be some more buy-in there.

Glen Stevens, DO, PhD: So I come to see you, you diagnose me, you say, "Yes, you have bipolar disorder." I'm doing my therapy. I've gotten off the substances that I shouldn't be on. My family's being supportive of me. You start me on a mood-stabilizing medication. Your flavor of choice didn't work. You switched me to a few different ones, helping a little bit, but still not working. What's the next step? How many drugs do we try before we do some type of other intervention?

Edward Kilbane, MD: Yeah, it's a great question. There is a group of studies called the STEP-BD, which is the Systemic Treatment Enhancement Program for Bipolar Disorder. And this basically looked at various studies over the years to come up with what are our guidelines for approaching treatment? And, certainly, there is actually a lot of polypharmacy involved at times. So we tend to start with mood-stabilizers. Those might be something like the salt lithium or some of the anti-seizure medications.

So we tend to start with those. But there's also a whole, another category of medications, which are the atypical antipsychotics. These were medications that were developed or came to market in the nineties, mostly, and have continued to do so since then. And these were, initially, for a different way to treat schizophrenia. They have a different approach, but they got FDA approval over the past 20 plus years also for bipolar disorder, some for bipolar depression, some for bipolar mania.

So, oftentimes, it is a scenario where you might have a combination of a mood-stabilizer and an atypical antipsychotic, especially if the patient's presenting with psychotic symptoms as part of their mood disorder. So I think there is a lot of room to try different agents simultaneously. 

But it sounds like, at some point, you're asking the question, what happens when these don't work? Most patients are treated in the outpatient setting. If that's not working and they're still having worsening symptoms, then there's a couple other options. One, before we get to inpatient psychiatry would be intensive outpatient programs. And those are kind of time-limited, sometimes several weeks or months, where a patient actually comes to an outpatient appointment, that's pretty much an all-day appointment. And they do that usually Monday through Friday for several weeks and get pharmacological management and also therapy management. So that's a more intense treatment, but not to the point yet where someone's at the inpatient psychiatric level.

If a patient needs to come into the inpatient psychiatric unit, there's two ways they can do that. So some patients will say that, "Hey, I'm not doing well. I'm depressed," or, "I'm not sleeping. I'm concerned I'm getting more manic. I need some medication adjustments done in a secured setting in a more expeditious fashion." That certainly is one way, they're saying they want to come into the hospital. They can voluntarily sign themselves into the hospital with the accepting physician. 

The other way that most patients come into the inpatient psychiatric unit is involuntarily, or not of their own will, and really by current Ohio state law, as a provider, you have to demonstrate that the patient is meeting one of three criteria. They are an acute danger to self, usually because they're suicidal. They're an acute danger to others because they're, say, homicidal or so aggressive. Or they're so decompensated from their symptoms that they're considered gravely disabled. They can't really tell us how they'd manage their basic needs, like shelter or food or hygiene. So those are the three current conditions that would allow any physician, many nurse practitioners and some law enforcement in Cuyahoga County to get someone to an emergency room and get them admitted to the inpatient psychiatric unit. Once they're on the unit, certainly, it's a matter then of pharmacologically trying to manage symptoms, and that can be done more effectively on an inpatient unit because dose adjustments can be made on a much faster basis than outpatient. Observation for improvement or side effects can be done on a daily basis by staff. If someone's not sleeping well, sometimes the use of sleep agents to really get them back onto a good sleep schedule can be used. And most importantly, it's a safe environment. So if someone is presenting with, say, bipolar depression and they're suicidal or bipolar mania and they're acting in such an erratic way that they might put themselves in harm's way, they're in a setting that's locked, that's secure, that's monitored, and where they really have a reduced risk of being able to end up in harm's way.

Glen Stevens, DO, PhD: So I'm not doing very well. You think I need to be admitted either for suicide ideation, just going off the rails, to some extent. What type of treatment option's inpatient, and the use of electroconvulsive therapy?

Edward Kilbane, MD: Yeah, so ECT certainly has a role. It is effective for bipolar disorder, for both depression and mania. It does come with the risks of anesthesia. And so it's not something that we just kind of jump to first line, but certainly can be helpful in cases that are refractory to pharmacological treatment. Cases that also present with catatonia oftentimes respond much quicker to ECT. In pregnant patients that are incredibly sick, ECT could be an option where you might not want to use certain medications because of potential adverse effects on the developing fetus. So ECT certainly has a role, not our first line as a go-to, but certainly has a role in helping.

Glen Stevens, DO, PhD: And transcranial magnetic stimulation? Inpatient? outpatient?

Edward Kilbane, MD: So that can be done outpatient. Yeah, that's an outpatient procedure predominantly. And TMS, or transcranial magnetic stimulation, is basically using a magnetic impulse that then, when it hits the cortex, is converted to electrical energy. So kind of acts like ECT, kind of like ECT-light, and it does not require anesthesia because you're actually not having an invasive procedure. And I believe TMS is currently FDA approved for major depressive disorder. There is a new type of TMS or a variant of TMS that's being studied for bipolar disorder, but I'm not sure that's FDA approved yet.

Glen Stevens, DO, PhD: Okay. Intranasal ketamine?

Edward Kilbane, MD: So intranasal ketamine is only FDA approved for major depressive disorder, not for bipolar disorder, currently, but there is really good evidence that ketamine can be effective, specifically for the depressive episodes of bipolar disorder. If we go back to what we were talking about, initially, that sometimes providers might want to pause about using antidepressants in bipolar disorder, but if someone's depressed and if the mood stabilizer, say something like lithium that has some inherent antidepressant effect, if that's not cutting it enough, certainly there's some pretty good evidence that ketamine does help with depression and does not run the risk of pushing someone into a manic episode.

Glen Stevens, DO, PhD: Psilocybin?

Edward Kilbane, MD: I don't think there's enough evidence for that yet. I mean, certainly there's some preliminary evidence for psilocybin for obsessive-compulsive disorders, for depression, but I don't think there's really good evidence, yet, for bipolar disorder. The other thing with psilocybin is when we look at states that have decriminalized psilocybin, it's really hard to know what content, what percentage of the active chemical, how that's delivered, what the frequency is. There's not a whole lot of guidelines as far as how often you dose, how much you dose, things like that to guide treatment.

Glen Stevens, DO, PhD: So it sounds like most of the treatments are depression-based?

Edward Kilbane, MD: Yes. Or mood stabilization-

Glen Stevens, DO, PhD: Or mood stabilization. Is it harder to treat the mania?

Edward Kilbane, MD: It is. I mean, harder than depression. I'm not sure how to answer that because they're both very difficult to treat. I think with the mania, the part that concerns me is that it can ramp up quite quickly and the behaviors can escalate and become quite dangerous quite quickly. If someone is increasing their substance use, not sleeping, doesn't see the issue with getting behind the wheel of a car or something, just the potential for adverse outcomes kind of increases exponentially.

Glen Stevens, DO, PhD: So I'm looking for the positive here. Do you age out of bipolar disorder or what happens over time?

Edward Kilbane, MD: You don't. I mean, it's a chronic disorder and it has fluctuations. But I think the important thing is that, for most people, the treatments that we have actually work quite well. And so I think it's a matter of finding a provider that you connect with well, finding a medication that works and doesn't cause such adverse side effects that you don't want to take it. Understanding that this is a chronic disease, so that if you feel better, you don't do what many people do, which is stop medications because why do I need them anymore? And then utilizing some of the psychotherapeutic interventions to figure out how do I go on living my life with this disease, like any other disease, in a meaningful way?

Glen Stevens, DO, PhD: Probably not an easy question to answer, but I'm on these medications, I want to get pregnant.

Edward Kilbane, MD: Yeah.

Glen Stevens, DO, PhD: What do you do?

Edward Kilbane, MD: So I mean, that's not an easy question, and it's actually one of the most frustrating things I encounter is when someone, especially who has a pre-existing diagnosis, say a bipolar disorder or any psychiatric disorder, decides to get pregnant, and sometimes the management of that does not go great. And some of that is that there is a bit of a knee-jerk reaction amongst all of us to try to pare down on medications for concern of how they might impact the pregnancy or the development of the child. And those are valid concerns, but I think they need to be weighed against what's the adverse effect of this patient becoming symptomatic during this period? 

So most of the evidence in pregnancy would be for lithium, to lower the lithium to the lowest dose possible that still gives some reasonable symptom control, try and get the individual through the pregnancy with that. That usually tends to work the best. Post-pregnancy, there's a question as to whether or not the mother is going to breastfeed, and if they do, that might help determine what medications you might want to use in that time period.

Glen Stevens, DO, PhD: And the other thing I was curious that you see a lot of smoking in schizophrenic patients. Do you see it in bipolar patients or no?

Edward Kilbane, MD: Not nearly to the extent that you do in schizophrenia, and we think that, mechanistically, there's something going on in schizophrenia where that excess nicotine helps treat some of the negative cognitive symptoms of schizophrenia, poor concentration, poor motivation. And that doesn't seem to be an issue in bipolar disorder.

Glen Stevens, DO, PhD: So I guess on a positive note, if I'm hearing you correctly, would it be correct to say the majority of patients that bipolar disorder can be managed-

Edward Kilbane, MD: Correct.

Glen Stevens, DO, PhD: ... with the disease and live a productive life?

Edward Kilbane, MD: I think so, yep.

Glen Stevens, DO, PhD: And new things on the horizon. What are we looking forward to?

Edward Kilbane, MD: Most of the medications that have been developed in the past decade or so have really been from that atypical antipsychotic class. There was, in 2021, a new drug, which was a combination of olanzapine, which is one of the atypicals that's been out for a while, but with samadorphin, which acts on the opioid receptor. In 2024, iloperidone, which is another type of atypical was approved. So we have newer stuff coming out, but down the road there is some interest in exploring further things like ketamine, which affects the glutamate system. Looking at some kind of neurosteroid modulators, there's one called zuranolone. As you mentioned, psilocybin. There's been some research looking at cannabis, although I think that's kind of a difficult place to wade into because the different types of cannabis out there and some of the negative effects that can have. So I think there are new agents that are being explored, but, right now, we're really looking at mood stabilizers and the atypical antipsychotics.

Glen Stevens, DO, PhD: Well, amazingly, our time is coming towards an end here. Anything that we haven't discussed you feel is important for the audience?

Edward Kilbane, MD: I just think anybody who does have these symptoms or family members that notice these in their loved one, don't feel shy to go talk to someone about it. It might be that you don't have a mood disorder, but if you do, it's much better to catch these things early, to get on treatment early, to manage it better, so it has less disruption on your overall daily functioning.

Glen Stevens, DO, PhD: Well, Ed, I appreciate your taking the time to walk us through the current diagnosis and treatment landscape for bipolar disorder. It's been very insightful and appreciate all the hard work that you're doing.

Edward Kilbane, MD: Thanks for having me on.

Conclusion: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's consultqd.clevelandclinic.org/neuro, or follow us on Twitter @CleClinicMD, all one word. And thank you for listening.