Chapter 1: Introduction and Bipolar Disorder Overview

GLOBAL NOTE: Highlighted passages represent KOL discussion sections that were built into the approved script/discussion guide.

Dr. Roger McIntyre: Hello, and welcome to the Psychiatric Times clinical consult video series on the role of long-acting injectables in the treatment of patients diagnosed with bipolar I disorder. I'm Roger McIntyre. I'm the Head of the Mood Disorders Psychopharmacology Unit at University Health Network and the Professor of Psychiatry and Pharmacology, University of Toronto. And I'm joined by two of my colleagues. Would you please introduce yourselves?

Hara Oyedeji: Hello, everyone. I'm Hara Oyedeji, a certified registered nurse practitioner at Fortitude Behavioral Health, specializing in behavioral health.

Dr. Todd Broder: And I'm Todd Broder, the Medical Director of University of Florida, St. John's Flagler Hospital, Mental Health Department and Co-owner of Florida Center for TMS.

Dr. Roger McIntyre: Great. Thank you for the introduction. I'm very glad both of you are here to talk with me with the latest developments in bipolar I disorder or BP-I and it's associated manic episodes. In this series, we will review the disorder and its impact, discuss common challenges associated with treatment and also talk about the importance of long-acting injectable or LAI antipsychotics as part of the management strategy. To that end, we'll dive into some of the data regarding LAIs and why clinicians should consider these agents as early treatment options for patients with BP-I. Before we get started, I'd like to note that this program is sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. and Lundbeck Pharmaceutical LLC. Now, we will begin this conversation with an overview of bipolar disorder and the importance of early treatment. Hara, why don't you get us started?

Hara Oyedeji: Thank you. Absolutely. And thanks, Dr. McIntyre. Bipolar disorder is a chronic neuropsychiatric disorder that affects 2.8% of American adults. In the past, many of us thought about this as an episodic disorder, but we have since learned that it's actually chronic. As most of you know, the condition is characterized by mood instability with recurring fluctuations between states of depression and episodes of either mania, which is typical of type I bipolar disorder, BP-I, or hypomania, which characterizes bipolar II disorder, BP-II. These symptomatic episodes are typically interspersed with periods of low-level symptoms or a state of remission. Manic episodes associated with bipolar can be particularly debilitating to patients. Mania often includes psychotic symptoms and can considerably reduce function across social and occupational tasks, thereby affecting the patient's day-to-day life with potential long-lasting consequences. Even just one manic episode can ruin a career, destroy one's financial status, or have legal ramifications. Relapsing manic episodes can be particularly concerning, and I'll share three reasons why. First, repeated manic episodes can reduce cognitive and functional abilities and increase overall disability. These impairments may be present not only during an episode but can also remain during remission. As the disease progresses, impairments increase. Second, manic relapse can create a snowball effect in which one episode leads to more episodes. And again, a higher number of episodes is associated with more damage and poorer outcomes. So it's very important to get in front of relapse. Third, relapse is a primary driver for psychiatric hospitalization, which is experienced by more than 75% of patients with bipolar disorder. Hospitalizations contribute to more than 25% of direct medical expenditures associated with care of bipolar disorder.

Dr. Roger McIntyre: So the key takeaway here is that it is extremely important to get in front of relapse with BP-I, both through early diagnosis and early treatment initiation. Dr. Broder, can you talk a little bit more about the importance of early treatment and by extension, early diagnosis?

Dr. Todd Broder: Absolutely. Early intervention has the highest likelihood of preventing disease progression and improving outcomes overall. Administering care early in the disease course is also important from a perspective of comorbidity management. Patients living with bipolar disorder, as we know, frequently experience several physical and psychiatric comorbidities, such as diabetes, metabolic disorders, anxiety, and substance abuse, all of which can contribute to the burden of disease and increase hospitalization rates. Therefore, early stabilization of bipolar disorder with treatment can help prevent complications associated with these comorbidities. Additionally, when an oral antipsychotic is used as the primary treatment, many patients are non-adherent to this treatment strategy, which can lead to relapse. These patients may experience improved outcomes with long-acting injectables, for example.

Dr. Roger McIntyre: Thanks, Dr. Broder. We'll talk about the role of LAI antipsychotics in BP-I management, but first, I want to hear some of your own practice insights when it comes to the practical implications of diagnostic delays and the impact on comorbidities. In your clinical observations, what are the short- and long-term cognitive and functional implications associated with uncontrolled manic episodes?

Dr. Todd Broder: So for me personally, I work primarily in an inpatient setting, and I know the focus very often is on the neurobiological degradation that can occur over time with ongoing manic episodes. As a forensic psychiatrist, one of the components I think very largely about are the social implications, as Hara was discussing earlier, of even one manic episode causing particular destruction to one's life. And I think those experiences become cumulative over time. So when I think about the long-term impact on someone's life, it may not just be cognitive, but it may be the cumulative social degradation over time.

Hara Oyedeji: I completely agree with Dr. Broder. Working oftentimes in community mental health, we often are treating the patient and having to deal with a lot of the social implications that bipolar disorder can definitely affect. And when one is experiencing a manic episode, it definitely can have, in the short term, those implications as mentioned with regards to career as well as school. I've been able to treat patients earlier on, but it definitely can be very disruptive. And there's also legal ramifications. Many times for those who are encountering manic episodes, the impulsivity can lead them to very risk-taking behaviors. But one of the pieces that often gets not overlooked, but one that we really need to address, is those who are the caregivers or the loved ones of those experiencing those episodes and how they too are very much affected.

Dr. Roger McIntyre: Thanks to both of you for that very helpful insights. Here's a second discussion question. What role have you found early bipolar disorder treatment to play in comorbidity management? Before you both maybe respond, I might just comment and say that we have some suggestion now that people living with bipolar I disorder have a higher rate of comorbidity after they've had multiple episodes of illness, which then in fact invites the possibility that early detection, diagnosis, and initiation of FDA-approved treatments might even prevent episodes or the occurrence of comorbidity. That's an interesting, I think, and testable hypothesis that maybe we can reduce comorbidity by early detection, diagnosis. But over to both of you, what role have you found early bipolar disorder treatment to play in comorbidity management?

Dr. Todd Broder: Dr. McIntyre, I couldn't agree more. And whether we're talking about bipolar disorder, schizophrenia, really any psychiatric condition, I think getting a handle on that very early plays a major role in comorbidities directly and indirectly. I think simply having stability in one's life gives them the wherewithal to follow up with medication appointments, to manage their health better overall, exercise, family, relationships. When those remain intact, I think that support system and network plays a huge role in patients managing their lives and comorbidities of other medical and psychiatric conditions.

Hara Oyedeji: Completely agree. As we know, early intervention, as with mostly anything, is really key. So the earlier we can get in front of a situation and intervene, we are better able to have a better outlook, a better prognosis. And once again, caregivers, family, those who are also involved are better able to assist the individuals who are experiencing that. So overall, it just makes a lot more sense if we're able to detect it earlier and treat.

Dr. Roger McIntyre: Wonderful. Here's a third related question. How has treating bipolar disorder earlier in the disease course affected comorbidity management?

Dr. Todd Broder: I think to somewhat reiterate what we've already said, and I keep bringing this concept back to family support, because when I look at some of these chronic mental health conditions, bipolar disorder and schizophrenia alike, and I think about the most valuable asset some of these patients have, often that is their family structure and their primary caregiver. And when these disease states and these conditions are poorly managed early on, I think there is somewhat of a fracturing or a scarring of some of those relationships. And helping patients to maintain that social structure early on, I think just creates such a nice framework for ongoing improvement over time and managing comorbid conditions as well.

Hara Oyedeji: Another piece to that really, and we alluded to that earlier, was the financial implications. It's not just to the patient themselves or their family members, it really is important on society. And so when we think about intervening much earlier and you think about the sequela that exists with bipolar disorder, or as Dr. Broder mentioned, other diseases in mental health, we really have an opportunity to really decrease that financial burden that exists on our clinics as well as on our hospitals. We are able to minimize and mitigate the chances for cycling and having multiple episodes.

Dr. Todd Broder: It's a great point.

Dr. Roger McIntyre: Really nice point and thank you both for your feedback. In the next chapter in this series, we'll explore common treatment strategies and challenges to bipolar I management.