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 To wrap this up for our audience, please screen every patient with depression patient for bipolar disorder, I can’t emphasize that enough. The sooner you can recognize and diagnose bipolar, the sooner you can institute effective evidence-based treatments. I like to start with FDA-approved treatments, and there is a lot of confusion around which drugs are FDA approved for which phases of the bipolar illness, so I would encourage you to look that up. As we have more of these options, it’s important to think about individualizing your treatment, not only for the mood state or mood episode, or the type of pattern that the patient has with respect to manias versus depressions, but also various comorbidities, and also as we talked about, patient preferences. It’s important to offer all the options and to get comfortable with using them.

I like to say that if I only had a 5 iron in my golf bag, I don’t think I’d be as good a golfer as I am with my full set of clubs. The more different tools, the more clubs you have in your bag, the better outcomes we’re going to have for our patients. I want to thank you all and wish you the best of luck with your clinical work.

 Thank you very much for your comments, Andy. As is usually the case in our conversation, time has just flown by. At this point, we will have to conclude. I thank our audience for watching this 

™ presentation, and we hope that you have found this presentation to be both rich and informative. Thank you very much, Andy, for joining us for this discussion.

Andrew Cutler, MD, shares his key takeaway advice to psychiatrists for the diagnosis and treatment of patients with bipolar 1 disorder.

Key Takeaways for Treatment of Bipolar 1 Disorder

 Andy, knowing everything you know, when would you suggest to our colleagues in the treatment algorithm—or are there any specific markers in our patients’ presentation—that would indicate we should consider using long-acting injectables [LAIs] earlier than people consider them now? When would you use them, and what markers indicate that long-acting injectables may be an appropriate choice?

 Realistically, we’re probably not going to use them in the first line with the first mood episode. Although in the schizophrenia world, we are moving closer to that first line, or certainly very early in the illness phase. We’re probably talking about people who are demonstrating a significant vulnerability to relapse, either because of the underlying pathology, that they have a more brittle or serious form of the illness. You spoke to the heterogeneity; bipolar disorder is heterogeneous. It’s unfair to say there are only 2 types of bipolar, there are many types. Or due to the other issue we talked about, which is the adherence issue. Patients who are demonstrating that they are vulnerable to relapse with oral medications, either due to the illness itself or to their difficulty with adherence. That’s where it would rise to the top for me, and I would probably try to think about it as early as possible. Based on what we just talked about, I’m not going to let somebody have mood episode after mood episode and potentially be doing damage to the brain.

With LAIs you don’t have to feel like you’re closing the deal the first time you bring them up. You want to think about starting a conversation and say, “It appears it’s been hard for you to stay on the medication, and it seems like you’re having a lot of these episodes. And what happens when you have mania is that you end up in the hospital or jail, but maybe there’s a way here,” and bring the patient into the shared decision-making. “Maybe there’s another option here that could help you get where you want to go and to not have these things happening to you.” You start the conversation. We have a very good friend, Peter Weiden, he is a schizophrenia expert. He once said to me, “Andy, you offer them an LAI the first time, they’ll say no. You offer the second time, they say no. You offer it the third time, they say no. The fourth time they’ll say, ‘Why didn’t you tell me about this before?’” That’s how to think about it. Also, it depends on how you present it. You don’t say, “Would you like an injection? Do you want a shot of your medicine?” You say, “Are you interested in a modality that has been shown to prevent relapse and the consequences of relapse, and that you only have to take once a month, or only have to think about once a month? By the way, it’s delivered by a long-acting injection.” I’ve found I get better success that way.

 On that note, you mentioned once a month. There is now a preparation that could be an every 2-month injection and may be comparable in efficacy to the aripiprazole option that is given only once a month.

 Yes. The one that is on the market now is aripiprazole monohydrate. It’s indicated for once a month. But now there is a 2-month preparation of the same aripiprazole monohydrate. It has a higher amount of aripiprazole in the syringe that you’d be injecting. I have seen pharmacokinetic data for schizophrenia that show it maintains a therapeutic level for a full 2-month interval. By extension, it’s reasonable to think that it would also hold a charge for bipolar disorder for every 2 months. That would be a wonderful option because people with bipolar disorder, as I mentioned, are often higher functioning. It may be more inconvenient for them to take time off from work to come in more frequently, and it’s nice to be able to check in with patients through telemedicine. You don’t have to bring them in every month, you could do a monthly in-between injection telemedicine visit and check in with them. I think it’s a wonderful option for our patients.

Vladimir Maletic, MD, MS, and Andrew Cutler, MD, share their insights into considerations surrounding the use of long-acting injectables in bipolar 1 disorder.

Current Role of Long-Acting Injectables in Bipolar 1 Disorder

 You mentioned a couple of important scenarios, one is nonadherence. We know that depending on the study, anywhere between 40% and 60% of individuals with bipolar disorder do not adhere to the treatment plans and recommendations. Another scenario you mentioned is a very important one, patient preference. Some patients may prefer taking oral medications. There’s also some indication that using long-acting injectables [LAIs] may cut down on the rate of hospitalization, which would also be an important consideration. Now, I have a very tough question for you. You mentioned 2 options, aripiprazole and risperidone long-acting injectables, and the evidence suggests that these medicines are quite effective in preventing recurrence of future manic episodes. But what about depression?

 That’s less clear because these trials tended to be in patients who had recent manic episodes. But in my experience risperidone is not as good an antidepressant as aripiprazole, but I believe that they both have some evidence of also preventing depressive episodes, particularly the aripiprazole studies. They are certainly very good options for that. The indication is for maintenance, which means to prevent the recurrence of either a manic or a depressive episode. If I were to use one of those two long-acting injectables, it’s very possible I might add something else such as lamotrigine to help stabilize from below. They’re both especially good at preventing manias, and they may also help prevent depressions.

 What I hear you say is that they do not exclude using some other agents to minimize the risk of recurrence of bipolar depression. How about the safety records of these medicines? I know you have done research with these compounds as well as use them in your own practice. What is your impression of the safety records?

 My opinion is that long-acting injectables are better tolerated than orals. If you simply think about the pharmacokinetics of an oral, the medicine has a lot of peak-to-trough variability, whereas the LAIs tend to have a much smoother blood level with less peak-to-trough variability. It’s not only about the peaks, at peak levels you can have more adverse effects, but sometimes it’s also about the variability in the peak-to-trough ratio. The brain doesn’t like things going up and down as much as it does more smoothness. There is some evidence that there may be less risk of movement disorders with LAIs, and the tolerability in my experience has been very good. One of the things I always wondered about was, we used to use haloperidol decanoate, and I found I didn’t see as much acute dystonia and movement disorders as I did with the oral version. I wonder if it isn’t this pharmacokinetic thing. In general, the tolerability has been quite good, particularly these two, which are not terribly sedating and don’t have significant amounts of weight gain. Patients with bipolar disorders don’t like weight gain and sedation. In the case of aripiprazole, you’re not elevating prolactin, so you don’t expect much sexual dysfunction. Patients with bipolar disorder also don’t like sexual dysfunction.

 Andy, as you know, there is much skepticism and reluctance among our colleagues, and long-acting injectables may be underutilized. You’ve mentioned some really good reasons why they should be considered: a favorable balance between efficacy and safety, cutting down on nonadherence, the diminishing hospitalization rates.

 There’s another thing we haven’t mentioned. There is evidence, certainly in the schizophrenia literature, that long-acting injectables may be better at preserving the brain and preventing deterioration. Now I tend to think of bipolar as potentially a neurodegenerative or neuroprogressive disorder. I had a professor once years ago who said to me, “Never let anybody stay manic or psychotic because they’re bad for the brain.” There is now evidence that may be true. As we know with subsequent manic or depressive episodes, you can see a decrease not only in brain tissue but also in cognitive performance. Use of a long-acting injectable may not only prevent clinical relapse, but it may also be disease-modifying.

 Potentially neuroprotective. As you mentioned there are studies looking at both number of episodes and duration of episodes. It appears that manic episodes are particularly toxic to brain tissue, but there’s also clear evidence of thinning of gray matter volume, and there’s a lot of prefrontal cortex involvement related to repeated manic episodes. Indeed, we do have imaging evidence supporting your claims.

Experts in psychiatry comment on the challenges of patient adherence to bipolar 1 disorder treatments and discuss the efficacy and safety of LAIs.

Safety and Efficacy of Long-Acting Injectables for Bipolar 1 Disorder

 For maintenance purposes, we have different kinds of antipsychotic medications available to us, long-acting injectables.

 Can you tell us more about where you see the role of these agents? What are the advantages and disadvantages? When would you consider using them over oral options?

 Let me start with an anecdote. I’ll never forget when I was first contacted to be an investigator on a study of long-acting risperidone, the microspheres preparation with every 2-week injection, for bipolar disorder, for maintenance. I thought that was kind of out there; I found that to be strange because I’d always associated the LAIs with schizophrenia and psychotic disorders. I thought I was going to have trouble recruiting for this study, frankly. I thought patients with bipolar disorder tend to be higher functioning. Are they going to want to have a shot? But I was surprised how many people with bipolar disorder, when given this option, accepted it. Those studies led to the FDA approval of risperidone long-acting microspheres preparation. We also now have an aripiprazole long-acting injectable, aripiprazole monohydrate. There are 2 long-acting injectable aripiprazoles, and one of them has been studied and is FDA approved for bipolar maintenance. The other one simply hasn’t been studied. That really changed my thinking. Sometimes I love when I’m proven wrong, when I’m flatfooted like that and don’t consider the options. It’s a failure of imagination on my part.

As I think about this, if we ask our audience, what is one of the biggest challenges you face in treating patients with bipolar disorder, near the top is going to be adherence. The fact is nobody wants to take medicine in general, and adherence is poor in all fields of medicine, diabetes medicine, hypertension medicine, and so on. But it’s especially bad in our field. I think some of it is that people don’t want to take medicine. Nobody wakes up in the morning and says, “Oh, I want to take an antipsychotic today.” But if you consider how this illness works, it is working on parts of the brain that have to do with insight and judgment. People with bipolar disorder are not often self-aware, they’re not good self-observers. They don’t always have the best insight and judgment, so they may think, “Well, it’s not that bad, I don’t need to take medication.”

So an option like this where you are guaranteed that they’re getting the medication, and you can tell right away if they don’t show up for their injection appointment that they’re becoming nonadherent, this can be an attractive option for some patients. Just like the APA [American Psychiatric Association] treatment guidelines for schizophrenia, they say a patient with schizophrenia should be managed with an LAI if they prefer such treatment. What that insinuates is that we offer it to them because how could we know if you prefer something if you don’t know about it? I think we should be offering them as a potential option because sometimes people don’t want to deal with the daily hassle of taking a medicine. Sometimes it’s more convenient to come in periodically and get an injection, and to not have to think about it, or not be in a situation where somebody can see you using a pill bottle and be stigmatized that you’re taking a medicine. These are some of the thoughts that go on in my mind now as opposed to before.

Vladimir Maletic, MD, MS, and Andrew Cutler, MD, highlight the use of long-acting injectables (LAIs) as a treatment option for bipolar 1 disorder.

Long-Acting Injectables (LAIs) in Bipolar 1 Disorder

 One recent study looked at the patterns of prescriptions of patients who have bipolar disorder in 15 years, from 2000 to 2015.

 You’re aware of that study, of course. There is an interesting trend, on one hand, supporting your view, the use of antipsychotic agents, especially second-generation antipsychotic agents has significantly increased. On the other hand, you have prescriptions for antidepressants.

 The part that is concerning is antidepressants without mood stabilizers have doubled in the last 15 years.

 Isn’t that incredible? The most common prescribed medicine for bipolar is a traditional non-mood stabilizing antidepressant.

 Often they’re combined with mood-stabilizing medicines and antipsychotics. Our colleagues clearly do not abide by guidelines. What do you think? Why are they prescribing antidepressants without a mood stabilizer, without a foundational agent for treating bipolar disorder? I’m just amazed.

 I think we have a semantic problem, and I think the DSM [American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders] does us no favors. I’m going to start with this: nowhere else in medicine would you do what we do in psychiatry. Nowhere else do you use the same word for a symptom, a syndrome, and a diagnosis. A syndrome is a collection of symptoms. For instance, I would not say you have fever disease, or fever, chest pain, cough disease, which is a syndrome. You would know if you saw that syndrome, that collection of symptoms, to look for the underlying diagnosis. And yet because we have an illness that’s called major depression and because we have a syndrome called a major depressive episode, I think we see a patient, and go, they’re depressed, great, I have this class of medicines called antidepressants, and my brain just wants to go there. That’s part of the issue. Semantically, people need to step back and recognize that when you have a patient with a depressive episode, you must screen for bipolar disorder because the treatments are different. Traditional antidepressants either don’t work or can make somebody worse. One of the concepts I like to think about the bipolar brain is not well-buffered. I realize that’s a very gross analogy, but it’s not well-buffered and so if you flood it with monoamines, it’s going to go off the road, is what I like to say. It doesn’t have guardrails, so you’ll go off into a mood episode. Same thing is true for significant postpartum depression or menopause, when women’s brains are having significant hormonal shifts. A woman with bipolar disorder will often go into a severe mood episode at times like that. I think that might be part of the problem, that our brain wants to go to an antidepressant. This is a problem with nomenclature, as we’ve talked about many times before. It’s unfortunate that we have a class of drugs called antidepressants and a class of drugs called antipsychotics. It’s just not the way they work. As you heard me earlier, I like to distinguish between what I call the traditional non-mood stabilizing antidepressants, which are predominantly reuptake inhibitors, and what I call the mood stabilizing antidepressants, which are some of the atypical antipsychotics. Another interesting fact is all the antipsychotics, whether first generation or second generation, work well for psychosis and probably for mania, but they don’t all have as strong antidepressant signal. That’s what I find fascinating because several of the newer atypical antipsychotics have been studied either as adjunct for unipolar major depression or for bipolar depression and there have been some failures. Then there are some that have had very robust antidepressant signals in that setting. I find that fascinating.

 It’s important that you’re making a distinction. While most will work for bipolar mania, select few, and I think you have mentioned olanzapine and quetiapine, and lurasidone and cariprazine, and more recently, lumateperone. Those agents have an efficacy in bipolar depression, but bipolar depression is a dominant mood state as you have pointed out.

Experts in psychiatry discuss the use of antipsychotics for treatment of bipolar 1 disorder.

Use of Antipsychotics in Bipolar 1 Disorder

What effect does obesity have on patients with 

? Results from a new study were highlighted at a poster presentation at the 2022 NEI Congress.

Michael J. Doane, PhD, and colleagues collected data from the 2016 and 2020 

 to examine the relationships between obesity and clinical, humanistic, and economic outcomes among patients who self-reported a diagnosis of bipolar I disorder (BDI). As part of the retrospective, cross-sectional analysis, participants (N=1853) were categorized as underweight or normal weight if their BMI was less than 25 kg/m

, overweight if their BMI fell between 25 and 30 kg/m

, and obese if their BMI was at least 30 kg/m

Doane et al used the 36-item Short Form Version 2 and EuroQol EQ-5D health surveys to measure health related quality of life. The Work Productivity and Activity Impairment questionnaire was used to measure work productivity and absenteeism as well as work and activity impairment. The investigators also leveraged the Medical Expenditure Panel Survey and US Bureau of Labor Statistics to ascertain direct and indirect costs.

The mean age of all participants was 34.1 years old, with patients in underweight/normal grouping tending to be younger than their peers in the overweight and obese groups. There were more females (65%) among the participants, and women were fairly evenly distributed among the BMI groups. Similarly, more than half (62%) of participants were white. Less than half of the participants were married (45%). The overall mean for being employed was 46%, and the percentage decreased as BMI increased. More than half of the overweight patients and obese were trying to lose weight and had exercised in the past month.

In addition to having the highest rates of high blood pressure, increased cholesterol, and type 2 diabetes, participants who were categorized with 

were more likely to have asthma, cancer, osteoarthritis, sleep apnea, and other comorbidities. They also reported the highest levels of activity impairment as well as the most number of hospitalizations and emergency department visits in the previous 6 months. Interestingly, when compared with the obesity group, the underweight/normal weight group had slightly higher levels of absenteeism (37.1 vs 36.4), and overall work impairment (64.3 vs 64.2). Not surprisingly, the highest direct and indirect costs were found in the obese group.

Doane et al acknowledged that individuals with BDI have an increased risk of obesity compared with the general population, which may be due to genetic, lifestyle, and treatment-related factors (ie, weight liability of medications used to treat BDI).

“[The] study results highlight important clinical, humanistic, and economic burdens associated with obesity in adults living with BD-I,” the researchers concluded. “These outcomes are important to consider in terms of a holistic treatment approach.”

Do you have tips for your colleagues on how to address obesity in patients with BDI? Share your success stories—or challenges—with us at PTEditor@mjhlifesciences.com.

1. Doane MJ, Thompson J, Jauregui A, et al. Humanistic outcomes associated with obesity among adults with bipolar I disorder: analysis of National Health and Wellness Survey Data. Supported by Alkermes, Inc. Poster presented at: 2022 NEI Congress. November 2022; Colorado.

How did patients with BDI and obesity fare in new research looking at quality of life issues? 

A Heavy Burden: Bipolar Disorder and Obesity 

 That is all excellent advice and insight. You’ve mentioned treatment of mania and any number of choices of antipsychotic agents starting with first-generation chlorpromazine all the way to second-generation agents. You’ve been kind to list approved treatments for bipolar depression and you pointed out that it’s important to keep in mind that not only do we have evidence of efficacy but also safety, but how about maintenance? You mentioned lamotrigine and lithium, what are some of the other medications that you would consider in maintenance of bipolar disorder?

 If we think about the traditional mood stabilizers, divalproex and carbamazepine are not actually FDA-approved for maintenance. I was an investigator years ago on a divalproex maintenance trial that failed, and there were methodologic reasons. They included people who were very stable, who didn’t have many mood episodes, and so what are the odds they’re going to have a mood episode? There wasn’t a lot of mood episodes to count here. I try to start with FDA approved. I like lithium and lamotrigine for maintenance. A few years ago, the APA [American Psychiatric Association] treatment guidelines for bipolar disorder said that antipsychotics should only be used acutely and should not be used for maintenance; now, that has changed. The thinking has absolutely changed, and we have several that are FDA approved for maintenance treatment of bipolar disorder. Often, I find if a medicine works acutely for a patient, it usually continues to work if they continue to take it. I’m more likely to stay with the medicine that help them in the acute phase, and then I might add to it. Most of our patients are on more than 1 medication, and bipolar disorders are difficult to treat with just 1 medication. The FDA requires monotherapy trials, so many of our medications are only approved as monotherapy. We have several approved as combination with either lithium or divalproex for mania, and we have 2 now that are FDA approved for bipolar depression in combination with either lithium or divalproex. Those are some of my thoughts. The other thing about maintenance is sometimes we must treat certain associated symptoms or breakthrough symptoms. Often you might be dealing with insomnia or anxiety or, as we talked about, some of the aspects of ADHD, and sometimes we are adding other medications to assist with that.

Andrew Cutler, MD, reviews the different types of medications for the management of bipolar I disorder.

Maintenance Approaches in Bipolar 1 Disorder

 Andy, you mentioned that use of antipsychotics. What are the scenarios where use of antipsychotics first-generation, and particularly second-generation, would be indicated as opposed to starting with the mood stabilizing age? Are there any clinical scenarios that influence your decisions?

 Absolutely. First, I’d like to try to start with an FDA-approved medication because then there’s evidence of both efficacy and safety. What’s interesting is when you poll audiences, they get this question wrong all the time, but what are the approved medications for bipolar depression? There’s 5 of them, and all 5 are atypical antipsychotics. Lithium, divalproex, carbamazepine, and lamotrigine are not approved for acute bipolar depression. That’s a situation where I’m absolutely going to reach for 1 of the FDA-approved atypical antipsychotics. Some of the antipsychotics are not approved yet for mania, but all antipsychotics in my mind are going to work for mania. Chlorpromazine in 1974 was FDA approved to treat mania, and antipsychotics can treat mania. I may have reached for an antipsychotic for mania, but my whole thinking has changed. I still like lithium and lamotrigine— divalproex hasn’t worked as well for depression for me—and so I reserve that for somebody with a real troublesome mania or frequent manias. It’s a good anti-manic if you will. I tend to use the atypical antipsychotics, especially because, while you’re right, it’s a funny quirk of the DSM [American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders] that you can be diagnosed with bipolar I with only mania. Most patients have recurrent depressions, and the depressions last longer, and the degree of impairment correlates more with a depressive state than with the manic state. I tend to lean towards using something that’s going to help with a depressed phase, perhaps prevent depression like lamotrigine, which can help prevent depression. It stabilizes mood from below. Those are some of the thoughts. I have certain ones of these approved atypicals that I lean more towards than others. If we talk specifically about the situation of anxiety, quetiapine has been a go-to medication for that if I can adjust the dose and try to minimize the weight in metabolic issues, for instance.

Vladimir Maletic, MD, MS, and Andrew Cutler, MD, review FDA approved medications for the treatment of bipolar I disorder.

FDA Approved Medications for Bipolar 1 Disorder

 We have talked about bipolar and comorbidities, what are some of the comorbidities that you screen for? And does it influence your treatment approach?

Absolutely, and actually that’s another one of my clues that I might be dealing with a bipolar patient. The 2 most common comorbidities are substance use disorders and both anxiety as a symptom and as a diagnostic category. When you see a real anxious, agitated depression, sometimes that could be a clue. The third most common is ADHD, usually if patients don’t meet full criteria for ADHD, most of them have some aspects of it, especially problems with sustained attention and working memory. They’re not demented of course, but they do have evidence of cognitive impairment. The fourth most common one, which I love to talk about in steakhouses, is binge-eating disorder. It’s true what you said about neurotransmitters, I think that there’s an element of dopamine dysregulation that goes on here. If you think about it, ADHD, substance use disorder, binge-eating disorders, these are disruptions of the dopamine system, especially motivation reward. That may be why some of our effective medications seem to stabilize the dopamine system.

 Andy, if our patient has a bipolar disorder with comorbid anxiety disorders or ADHD does it influence your treatment approach?

Absolutely, yes, and we should talk about that. First of all, there are 2 large meta-analyses now that look at adding stimulants to patients with bipolar disorder. They found that if the patient is adequately mood stabilized, either with a traditional mood stabilizer or atypical antipsychotic, adding the stimulant not only does not hurt the patient it actually improves their mood, their attention, and various other aspects. That is a situation where I’m a lot more comfortable treating ADHD as I would ADHD without bipolar disorder. Of course, they must be adequately mood stabilized, and I must be comfortable that they’re not going to be actively abusing the medication. For anxiety, that may influence my choice of the baseline, the foundation medication. I tend to use atypical antipsychotics as a foundation, and then I’ll add either lithium or lamotrigine, or perhaps divalproex; they are some of the atypical antipsychotics that appear to be better than others for treating comorbid anxiety. Now we must open the Pandora’s box for a second of a traditional antidepressant. One place where I think there may be a role, specifically for SSRIs [selective serotonin reuptake inhibitors], is somebody who has a real obsessional anxiety picture. A little serotonin may help with obsessionality, but in general, I try to avoid what I call traditional antidepressants or non-mood stabilizing antidepressants. The short answer to your question is absolutely that’s going to influence my treatment, and I think we need to individualize our treatment plans.

Experts in psychiatry discuss common comorbidities associated with bipolar I disorder, highlighting substance use disorders and anxiety.

Treatment Approaches to Bipolar 1 Disorder and Associated Comorbidities

 You opened a very interesting discussion, and I hate to say it, who could fill up the entire hour with that discussion, but I think you’re making a very good point. That is, as we elucidate some of the pathophysiology underlying bipolar disorder, we are realizing that symptoms of bipolar illness map more easily on dysfunction of a functional brain network and their communication than they do to transmitter systems. To provide a global picture, it appears that in a manic state the network has heightened activity, and this may translate into sensory acuity. You have seen it in our bipolar patients where people chewing loudly, conversation at workplace, and any sounds in the background including ticking of the clock can be innervating. In addition to that, there are issues with increased motoric activity in mania. These individuals are restless and agitated and often pacing. On the other hand, salience network also seems to have heightened activity, and therefore there is possibly a relationship with grandiosity where one believes that one may have been slighted yesterday by not being granted Nobel Prize for one’s discoveries, and maybe this year is not our year, but next year it’ll definitely be. People tend to be expansive, overly interested in enjoyable activities, so sensory motor network in mania seem to have elevated activity. Additionally, default mode network, which in part has to do with self-reflection of monitoring, seems to have decreased activity in mania.

 It’s the opposite, exactly. For sensory motor activity individuals, when it comes to sensory cues from the periphery diminish sensitivity and somewhat increase sensitivity for internal stimuli. People tend to be preoccupied with bodily aches and pains, but when it comes to motoric activity, as with psychomotor retardation, it’s often reduced in depression and salience in terms of finding meaning in terms of having emotional echo in the events in one’s life; interest is lower, enthusiasm is lower, ability to enjoy life is lower. On the other hand, heightened activity, and default mode network, which is sometimes associated with ruminations. Nonproductive reviewing of the Rolodex of miserable events in our lives which does nothing but deepen heart depression. The part that is intriguing to me is, in these large genome-wide association studies, it has been appreciated that bipolar disorder, like other psychiatric conditions, is not homogeneous. Individuals who have bipolar disorder will have risk genes for MDD [major depressive disorder, for ADHD, for substance use disorders, and schizophrenia. There are studies that have looked at individuals, top 10% highest presence of schizophrenia risk genes versus bottom 10% lowest presence of schizophrenia risk genes, and in terms of response to lithium, individuals who had highest presence of schizophrenia risk genes have three and a half full less chance of responding to lithium.

Less chance quite interesting. I wasn’t aware of that.

 Versus individuals who don’t have schizophrenia risk genes that have bipolar disorder, so not readily translatable to clinical practice.

 How often have you had patients with bipolar disorder who didn’t respond to lithium, but did respond to either typical or atypical agents?

Yes, absolutely. It is fascinating. It would be nice, wouldn’t it, if we had some biomarker like that to guide us to an appropriate therapy?

 Indeed, and phenotypically there is no clear-cut separation. There is some suggestion that there is mood incongruency between delusions and patients’ mood state. But again, that is not a reliable phenotypical marker.

Drs Vladimir Maletic and Andrew Cutler explore symptoms associated with bipolar I disorder, such as sensory acuity, recurrent depression, and manic episodes.

Bipolar I Disorder