Welcome to the Psychofarm podcast. This podcast is for education and entertainment. It certainly is not medical or psychiatric advice, diagnosis, or treatment. Listening does not create a doctor-patient relationship with me or Dr. Fu. If you're a patient, certainly don't change your treatment plan because of something you hear in the show. If you're a clinician, do not use this podcast as a clinical reference or substitute for your own training, judgment, thinking, and up-to-date sources.
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Are you winning? Actually, if one defines winning as having had a great time with very good people and feeling good physically, oh yeah, winning
big time. That's a very nice answer. What are your strengths and weaknesses on the court?
Oh, I'm supposed to admit those to you. Some tennis background, you know, so that helps, but one can always use better backhand. Backhand.
All right. Interesting. I'm all backhand. That's a ping pong background. Yeah. So yeah, let's jump into our topic today, which is hypomania. And I think there's especially people are, I think people want to learn more and more about bipolar, especially with the Lindsay Clancy case. I don't know if you've been following that at all.
I am indeed. It's so, so sad to see, first of all, of course, what happened, what that poor woman and her, everyone around her must be going through. And then what's happening with journalism around it and the court of public opinion. Yeah, it's awful. And hopefully maybe we'll end up being helpful in some way. Raise public consciousness.
Yeah, it's an absolute mess. And you know, it's made me think of sometimes these sort of terrible things need to happen to raise awareness. The reason why we're also worried about serotonin syndrome is the case that happened. There was a resident who didn't sleep and then they gave the patient a medication that interacted and caused serotonin syndrome and it kind of blew in the spotlight. And it's these major cases that kind of bring public awareness to these conditions.
True. Yeah, sadly.
Right. So I think there's more interest in kind of understanding bipolar, screening for bipolar. And I think hypomania is a good understanding hypomania is a good entry point to kind of these discussions. But all that aside, can you talk to me when you say hypomania, what are you talking about?
Well, nominally, it's the versions of mania that are short of the threshold for mania, right? But the problem is, if you take a spectrum approach to conceptualizing mood disorders, you immediately run into this problem of hypomania as a spectrum of variations. And so the upper end bumps into mania. And, you know, you can kind of fuss around whether it's bipolar 1 or bipolar 2. How close to mania did this hypomania get?
And the easy threshold is, was there anything destructive, damaging, dangerous... Negative consequences. How much would a person want to really avoid having that happen again? If it's like, oh, yeah, for sure needs to be avoided, I think that takes you into the bipolar one that was manic. It's got some destructive potential. It destroys relationships, money, jobs, and so on. Short of that, then you're in the realm of hypomania.
But the big problem is down at the other end, if you admit that this is a spectrum of variations, I think amongst mood experts, there's no quibbling about that anymore. Then the bottom end takes you into, well, where do you go when you get to the bottom end of hypomania? You end up in, oh, there's no hypomania at all, so it must be unipolar, which is false.
But there's just no hypomania there anymore. Okay, now we have a different differential to pursue. Is there a potential for mixed states, rapid cycling? But at least we can say, to the best of our ability, there was no hypomania present. If we assert that there is a spectrum and we looked all the way to the bottom. Well, that's a nice idea, but what are you looking for when you're looking for the bottom?
You're looking for something that is so subtle. It is definitely a part of everybody's daily human experience at one time or another, like having a really good day. If the difference between having a really good day and being hypomanic is so slim that it's basically undetectable, then how are we supposed to make this diagnosis? That I think is the fundamental problem of hypomania.
I hope that you're going to help us answer this problem.
I do have some approaches to it, but the very first is to admit that Ruling out hypomania is effectively a fool's errand. It's impossible. How can you say something isn't there when it is that subtle in terms of its manifestations? Like, oh, you know, so I'm talking a little fast. I'm thinking lots of ideas. I slept a little less. You know, I had difficulty... of getting to sleep because I had so many ideas on my mind.
I felt really productive. I called some people that I haven't talked to in a long time. Well, I would hope that all of us do that, something like that from time to time, have an energized state or really good day or the more The negative experience of the very same thing. So agitated, irritable, anxious, having difficulty focusing because too many thoughts are flying around. So it's not always a euphoric hypomania, even at that very subtle extent.
So the first step then is to admit that Ruling out bipolar and being able to say for certain that it is not there is logically impossible. How much time did you spend looking? How did you look? So that's the first problem. So again, we admit that we really can't do this.
The second reason this is so impossible
is because there's a famous study from Louis Judd from back in the 90s and Judd and colleagues in which they asked people to Retrospectively, each week, rate their mood manic, depressed, or euthymic, or mixed, and manic includes hypomania, looking back for the past week, and do that for a year. And this is in bipolar II. Have you seen this study? There's a famous Venn diagram that shows you that half of the Venn circle is euthymic.
Every week, they're reporting their mood, and half of the time, over the course of this year, they reported that the previous week was free of either mania, hypomania, or depressive symptoms. The other half, this is in bipolar II, was depression, all depression. Euthymia or depression, that's bipolar II, except for this 1% of the time wedge of hypomania. So the lived experience of bipolar 2 for a year, 1% of the time was retrospective on the part of the individual recognizing hypomania, 1%.
So not only are we looking for something that's so subtle, it's basically part of normal human experience,
but we're looking for something that happens 1% of the time.
We should just admit that is impossible, which means that ruling out bipolar Is impossible if that's the way you're going about doing it. That's the dilemma.
Yeah, and you bring up such, because I get asked all the time, like, what's that magic question? What's that magic screener question to rule out bipolar? And I think, I'm so glad that you're pointing a voice to that.
It doesn't exist. Yeah, you can't do that with confidence. What you can do is gather all the other data that will help you Adjust your assessment of probabilities. And you're trying to get the greatest confidence either because, of course, we're making a treatment decision, right? At some point, if not initially, then down the road, not short, not too far. So at some point, you're going to have to try to push this into a dichotomy.
Are we going this direction? Are we going that direction? But initially we should admit that we're gonna have difficulty doing that. And all we're going to be able to do is maximize the probability in one direction or another. Now, okay, is that just a, oh, well that's making a diagnosis and all I did was just split hairs. No, I think what we need to do is in your initial interview, recognize that it's very unlikely that you can be certain at the end of initial interview Bipolar or not.
And arrive at a treatment decision in the very first interview, very unlikely. If you're forced to do it because of an inpatient setting, then you're going to need all the rest of the stuff that you and I are about to talk about. These other ways to assess how much bipolarity is present.
I'm so glad you're bringing this up. And I talk about this in earlier episodes of this podcast, that as I get more and more experienced, the amount of uncertainty I have goes up and up. And the amount of times that I communicate to patients, I say almost at the end of every intake, I wish I could talk to someone for 45 minutes and tell them all their problems.
Unfortunately, the world doesn't work that way. And if we work together for a longer time, I'll be able to get closer and closer, I hope, to what I think is a definitive diagnosis. But that's going to take some time. So you mentioned, ultimately, as clinicians, we have to make a decision which road we're going to go down. Is it the major depression road or the bipolar road?
What are the things that push you
in one road or the other? So there are non-manic markers. In other words, we're going to move away from the symptom-based assessment that is the DSM. To other findings in the history of bipolar disorder, as we've understood in the last hundred years, other findings that are associated with a bipolar diagnosis, down the road, once the diagnosis becomes firm, what could we look back and say, oh, well, when these things are present, the probability of a clear-cut bipolar outcome down the road is higher.
What things are those? And they're not in the DSM. There are four of them, and the When you put them together with symptoms, which count, they don't not count, especially when clear-cut manic symptoms are present. But the other four of these five dimensions, I think of them as the non-manic markers. And you've heard these before, and I hope most of your listeners will have heard them before.
But I think it's important to conceptualize these things as these five dimensions. This is what you need to characterize for everyone with a mood problem and, frankly, most people with an anxiety problem as well. And the five things are symptoms. We just talked about how that alone won't nail it down. And then age of onset, what was the age of which the person had their first problems with depression?
We don't have to worry about your first mania, because if we can identify that you've had one, then we're not fooling around about the diagnosis anymore. Age of onset means first episode of depression. Family history. Is there anyone in there who's got, well, a first degree relative with a shortcut diagnosis of bipolar disorder? That would be nice. But, you know, of course, this is the realm of fuzziness as it's part of our job.
So we're going to hear other things. Well, there's been people with mood problems. There may have been someone with a suicide with no clear diagnosis. There may be people with really wild behaviors that you know uncle Max. He was a trip and I'm listening, but you know that won't nail it down for you, but it's again these are just adjusting probabilities so age of onset family history and, of course, the closer.
A relative as opposed to a second or third degree relative, the more meaningful whatever you're finding will be. So age of onset, family history, course of illness. Course of illness means how up and down is it or is this an episodic mood problem or is this the first episode with no prior mood problems? That would be a fairly strong negative in terms of bipolarity. Of course, the first episode in a young person, that's different.
Now we're looking at that early age of onset. So cyclicity, really important. I'm sure you've heard this phrase before. It comes from, I think, from Fred Goodwin, the former head of the National Institutes of Mental Health, who wrote the Bible of manic depressive illness. He said, cyclicity is more important than polarity. This is more important than that. Try to define whether or not someone's had a manic episode and define bipolar disorder on the basis of, no, I couldn't find a manic episode.
That's the wrong approach to this mood spectrum. We're looking for how bumpy is it? Highly recurrent, apparently unipolar depressions. That's a bipolar phenomenon in the same way that one can have Manic episodes and never have a depressive episode, and yet we still call it bipolar. It's unipolar mania. Well, you can have unipolar depressions, but if they're like this, that's a more bipolar-like phenomenon because cyclicity is more important than polarity.
If people take away one thing from this podcast, patients or providers, I think it's focusing on the cycling as the treatment goal and not the particular symptoms. I hope that's the one thing you take away. And I say this with every patient with bipolar, we're focusing on less ups and downs, not on a particular how you're feeling that day. And that totally changes the medications and everything.
But that's the one thing I think is so important for everyone to take away.
Good, absolutely agree. Well done. You're echoing Gary Sachs. He is the head of the STEP-BD program, the big research program on bipolar disorders for the National Institutes of Mental Health. So at one time, Gary Sachs was like the guru of bipolar disorder, and you just said exactly what Gary Sachs has said. Do not focus on the mood du jour. Focus on the cycling, stop the cycling, and then you have to reassess.
Maybe you're going to stop the cycling and there's still a depressive component there. It could be a dysthymia associated with a horrible childhood trauma history. Now you have the challenge of addressing that depression without reinitiating the cycling. But first get the cycling quiet because if you don't do that, you're gonna be chasing the cycling the whole way with these usually antidepressant efforts. So yeah, stop the cycling.
So those four non-manic markers, age of onset, family history, course of illness, and lastly, response to treatment. Well, if you knew that a mood stabilizer worked great, that would be fine, but we're usually not in the position diagnostically to have that information. So what we're really looking for in this response to treatment finger is an adverse reaction to an antidepressant. Something weird happened. What a primary care colleague called antidepressant misadventures.
Oh, you know, something really strange happened. That's all I'm listening for. I'm not listening for an induced manic episode. I'm not listening for a recognized induced mixed state or hypomania. Just something I couldn't sleep. My mind was flying. I felt really agitated. Of course, all of those can happen when one starts an antidepressant and they don't necessarily mean You have to stop it. They don't necessarily mean this person has an underlying bipolar, but they change the probability in that direction.
So those four, the non-matic markers, age of onset, family history, course of illness, results of treatment, I wish everybody in psychiatry would be able to rip off those four things just in the same way that we can do, what was it, you know, dig fast, CIGI caps, all those acronyms that we've learned. Family history, age of onset, course of illness, response to treatment. Everybody ought to be able to do that without even thinking because those are the dimensions you need to assess in addition to the symptoms.
And that's true across all illnesses.
I actually, I want to hear you talk more. I apologize. I'm going to steer us off course a little bit. So you mentioned like an abnormal response to an antidepressant. When, let's say you start an antidepressant, what sort of things push you into stopping it and going the bipolar route? Because I do see a lot of patients having Have increased anxiety, decreased sleep, a short period of kind of having difficulty adjusting the medications, and we push through it and it's fine.
What is your line for saying like, hey, I think this is representing an abnormal response that we can call as a result of bipolarity?
Yeah, important question. Thank you. The answer is it depends on what your index of suspicion of bipolarity was before you started the whole thing. If your suspicion was very, very low, then you can, you and your client patient can kind of tolerate some of this and explore and carry it on a little farther and see what direction this is going. If your index suspicion was high and yet you started an antidepressant anyway, which I would hope you would do under only Because you've tried a zillion other things and you and Incon are desperate.
So you can see, it depends on where you started. And I would hope that people would be very hesitant to start an antidepressant when the index of suspicion about bipolarity is quite high. So on the other hand, yeah, it'll happen. And then you just do it with caution. And now you really have your ears step forward to those, any adverse things happening.
I love that. And I think when I do this with patients, I show my thinking. You know, like, well, when I see they're kind of moving their own direction, depending on the risk level, like you said, if this patient's very high risk for something really bad happening, then I might be a little bit more paternalistic and being like, we're stopping this and going a different route. But for a patient that they're low risk, there's room for error.
I show my thinking and I say, what do you want to do? Obviously within certain parameters.
Yeah. Yeah. Good.
Now, a big question that comes up and might seem a little silly. So here we're talking about bipolarity. What does that mean? When we say there's some bipolarity, there's a spectrum of bipolarity, bipolar one, bipolar two, what does the word bipolarity mean?
Well, so we used to talk about the bipolar spectrum. It was common in the literature. But I think a better way to think of it is the mood spectrum because really there's no dividing line between the bipolar part and the unipolar part. It's a continuum from one end to another. So bipolarity is the pigment in your basic paint color that shifts it from being white in the direction of red.
And you can have any amount of that pigment dropping into your basic white paint color. Including zero, in which case you'd be down there at the unipolar end. So bipolarity is like a pigment that you drop in. What does that actually mean? Well, amongst the determinants of bipolar that we're learning about in terms of like what causes it, that means People have progressively more of these things, more of a genetic predilection toward it, more of an inflammatory state that places them at risk, more of a metabolic state, for example, type 2 diabetes that places them in a different metabolic state, including brain metabolism or glucose.
Reward hypersensitivity. I'm ticking off the five dimensions, the five things that were now recognized as cause bipolar. Genes, inflammation, metabolism. Reward hypersensitivity. People with bipolarity have an increased probability of latching on to the potential for reward, overestimating the probability of a good outcome. Reward hypersensitivity. And then lastly is circadian differences in circadian rhythm, a tendency toward night owlness and a lower amplitude of their circadian rhythm, such that it's easier to get out of phase with the rest of the world.
So bipolarity means you've got more of those things, a lot of one or some of each.
Mm-hmm. And then the big treatment implications of saying there's some bipolarity or a lot of bipolarity. What would you say are like the big treatment implications there?
The biggest one for sure is how likely is it that we're going to make you worse with an antidepressant? And conversely, to the extent that we worry about that, then we think that maybe a mood stabilizer based approach is a better idea. So are we going after the depression per se or going after mood stability? With an eye, of course, on the depression component as a big part of the problem.
So you talked about the big things that you're looking for that suggest bipolarity. And then I guess the question to me to move is you mentioned like we're branching off of are we going the MDD treatment route or the bipolar treatment route? What's the line for when you'd move from one to the other? I like asking you impossible questions.
Well, you know, it is the question that we face when some people show up with depression, and we ought to be thinking about it when people show up with anxiety as well. Particularly if you're kind of boxed into being a pharmacotherapist, and so you're really thinking about an antidepressant or some other approach, This is the question you have to ask. Now, of course, I'd like us to all try to unbox ourselves so that we're not just pharmacotherapists, so that one of the first options is a psychotherapy approach.
We have lots of tools that don't require nailing it down so much in terms of, well, how bipolar is this? It could be, yeah, maybe it's a little bipolar, but if you want to start because there's a trauma history with Cognitive processing therapy or written exposure therapy or even EMDR, fine, because none of those is likely to make bipolar worse and may help some. You might lose a little time and that's an issue.
But so when we have psychotherapy tools at our hands, either in our own hands or we can easily get our patient client to someone who can do those things, That takes the pressure off of making that decision about antidepressant or no. But yeah, you're trying to get me, Dr. Malzenberg, to go, where is the decision point? And it is, I have assessed all five dimensions. Symptoms, that's the dig fast stuff that people are used to doing.
Agent Vaughn said family history, course of illness, response to treatment. I've assessed all of that. If there is still some doubt, I would try as hard as possible to wait to commit to a pharmacotherapy approach and go get collateral information from some source because of that. You know, people recall 1% of their time was in hypomania over the last year, but they may well have been in hypomania much more than that if somebody else could tell us about it, why they're relying on their own history.
So there's a nifty instrument for that. The HTL32, the hypomania checklist has 32 hypomania symptoms. And if you just make yourself a one page HTL32 and you can say, take this home and have somebody else say whether you are ever like this. If I'm having difficulty making that cut, which way are we going to go? I would want to do something like that. If I possibly could before I committed to the direction.
But in other words, the very short answer is you gather all the data and then you share your thinking as you were just describing, Dr. Malzberg. You share your thinking process so that your patient can participate in that. Well, how certain are we and what are my treatment options and what are their pros and cons? That becomes part of the decision making process, especially when uncertainty is high.
Now, you mentioned the HCL. So I was about to ask, what sort of things do you ask? Let's say you do have the patient's family in front of you. What are, I guess, the big ticket items? What are the things you hear that point you into the direction of hypomania or not hypomania? Or is it worth kind of just going through the whole thing? I guess, do you have any big questions that you find kind of squeeze some juice out of what the answer is?
Well, so in the courses of assessing symptoms, you'd have been asking something about phases of relatively higher energy, be it anxious or productivity or thinking or just energy underneath your skin. And then whatever you're hearing, you just go further with it. Tell me more about that. Rather than using a checklist, I'm just using... Really good listening, right? Tell me more about these things that sound like you're just a bloodhound chasing a scent.
So that's, I prefer that to a checklist, but the checklist can bring up things that neither the client or patient, I'm used to talking with psychotherapists nowadays as much as physicians, so I end up with this, sorry, juggling the term. They are not likely to think of this as not normal, and we might not think to talk about it, but HCL32 can help us in that respect.
Ian, I like the scent of the hound, because I think it really points to the fact that you can't be a million percent confident, because there's so many patients that I hear a common example is, you ask the question, trying to find that hypomania, and they go, you In college, there were three or four nights that I wasn't sleeping. You're like, oh. And then I was drinking a lot.
And it's like, oh. And then I was super stressed over finals. And it's like, you're just kind of going back and forth. And then you walk away being like, they We're a little blurry and like every single thing. And I maybe it was just the drinking. And they say, like, you know, all these things that you kind of go back and forth. But I like I like how you're pointing that there's not one thing that it's like, boom, done.
You're collecting a full range of evidence, not just relying on this one story or this one event.
Yeah. Now, I've been accused of having bipolar lenses. That everyone whom I see with a mood problem or an anxiety problem has bipolar disorder, like until proven otherwise. Well, actually, that is how the GSM works, right? You have to prove that it's not bipolar before you can call it unipolar. So from a logic point of view, that is, it is fair to start out with bipolar lenses.
But particularly since I have a predilection toward finding it, in part because the people whom I would end up seeing, I've already had two, three, four, five treatments. And Why do another unipolar-based treatment? If we could substantiate the potential for bipolar, we could support the idea of taking a mood stabilizer-based approach. So yeah, I'm looking for bipolarity all right. But in order to defend against overdiagnosis in that respect, I can turn the logic tables around the other way and say, ultimately it becomes incumbent upon me to disprove my My potential leap to the diagnosis.
So as you were saying, you're listening to this history and there were a couple of nights in college and now I'm on the bloodhound trail and I'm sniffing along. And if I keep getting positives, then I need to switch my orientation from I want to find more positives to I should be able to look for negatives, like really big negatives that would make me just drop this idea.
Like I just did great on an antidepressant for a long time. With no problems. Like, well, I can't justify not going back there in the face of that, even if I've got a fairly strong scent of bipolarity.
You mentioned, I've made the joke before that in psychiatry, an expert is just someone who can find what they're an expert in, in anyone. You know, I give ADHD experts and everything's ADHD and bipolar experts, everything's bipolar. But I think of the experts, you are very well-rounded. You are not, I don't think you have the lens, but.
But knowing one's predilection and knowing that one should actually be trying to disprove one's own hypothesis is just the way science works. We should remember that.
I also like in another, I was listening to something that you said, like, know your own biases and be aware of them. I think this is a reference to ADHD. I also know that I can be dismissive or feel like ADHD is Yes, good. So we're talking about hypomania, and I feel like I kind of want to move on to mixed states because I feel like it's partially related because once you hear more about mixed states, I feel like you're able to see it.
I think it's one of those things that like learning about it, then you kind of see it all over the place. Can you talk to us a little bit how you think about mixed states?
Righto. Again, thank you for the invitation here today and for that question. Well, so mixed states. Conceptually, they are the territory that is not bipolar II but not unipolar, right? So you're somewhere south of being able to substantiate enough hypomania to call it bipolar II because if it's bipolar II, then yeah, you could have mixed states within bipolar II, but you know it's bipolar II. What the big problem territory is mixed depressions.
You can have mixed mania, right? It's like a negative, you know, anti-diotic, paranoid, irritable, definitely not euphoric mania. That would be a mixed mania. A dysphoric mania, we could call it. So mixed mania, but you don't treat that fundamentally different than just plain old mania. So I kind of dismissed that as part of the mixed state problem. The big problem is mixed depressions because you're right down next to unipolar.
In fact, finally in the DSM-5, they got as close as they possibly could to you saying, yes, it's a spectrum by saying that there's this thing called major depression with mixed features. Oh. Oh, that's a bipolar thing. And it's right, oh, it's in unipolar land. Well, what they were doing was defining this territory, this like short of bipolar, but not unipolar. Well, okay, that's a spectrum then, right?
And there, of course, there's many variations of mixedness where you can have just a little manic symptoms or a lot of manic symptoms, but not necessarily quite enough to get yourself a diagnosis of bipolar disorder. So we're just struggling with the like mixedness is just admitting it's a spectrum. But there are some particular mixed-state symptoms that have emerged in the research since the DSM-5 came out in 2013.
We're now 13 years later. So there's four symptoms of bipolar, like manic-type symptoms that appear in Otherwise, what appears to be unipolar major depression. Those four things that really make a mess of this territory. And the four things have been defined by Roger McIntyre from University of Toronto. He's given multiple presentations about this. He's written it up in Lancet. The four things are anxiety, anger, Agitation, Physical Agitation, and Attention Problems.
He puts them that way to make the four A's. So once one admits that the four A's, anxiety, anger, agitation, and attention problems can be manic symptoms in unipolar, this is part of a bipolar mixed state. Man, once you admit that, now you have a diagnostic overlap with You know, major depression plus PTSD with an agitated state, major depression plus generalized anxiety disorder with an anxious state, major depression with attention deficit disorder with irritable phases, major depression with borderline personality disorder with phases of variety of symptoms.
So the diagnostic overlap problem, once you admit of the four A's actually being Admissible symptoms to make it mixed, because not all of them are in the DSM-5, but subsequent research says that, yep, they're there. Well, once you admit that, you have a diagnostic mess. So that's why we should talk about mixed things. Can you please clean up this mess for us?
Because it's both a super, it's an incredibly helpful concept. And I use the 4As all the time talking to patients. But I'm excited for you to help clean this up because yeah, it does have such crossover with so many other conditions.
Yeah. So first thing to do, and I should send it to, because I'm really, I'm not proud to have made it because I used AI to make it, but I asked AI to make me a graph of, suppose you have On the mood spectrum, the probability of symptoms based on national epidemiologic data. How many people are over here in unipolar land? How many people are over here in bipolar land?
Let's give me an axis like this. Now give me another axis of how anxious are you? People can be a little anxious or a lot anxious. A diagnosable like GAD level of anxiety is 50% common amongst mood disorders anywhere on the spectrum. So there's a mood spectrum and then there's this anxious component. And when you make a three-dimensional diagram of just those mood and anxiety symptoms and then plot it based on the prevalence of those symptoms and their degree, you end up with this cloud.
And the cloud is... It's like, oh, there's people all over the place in here. And there's a mixture of depression and anxiety and it's more medical than over here and it's more anxious over there. And then the GSM plucks out these corners of the three corners of this thing. It says, these are the diagnoses. So the cloud recognizing that it's a cloud and then saying on that basis, we are not going to be able to be certain.
Uncertainty is wisdom. And you were just talking a little while ago about how you're willing to share your uncertainty with your patient because it's, I think, a very transparent and important starting place when we're trying to make a treatment decision. So uncertainty is wisdom. That's the first place to go when you're thinking about, uh-oh, is this depression with PTSD, depression with JD, depression with ADHD, and so on.
That's the first place. Uncertainty is wisdom. And relax into that. It's okay to be really uncertain. In fact, it's really actually probably a problem to be certain. It just distresses me so much when I hear residents say, oh, you know, she's not bipolar and toss it off as though that's easy to say. That's really hard to know. Okay, so uncertainty is wisdom. That's the starting place. And then I think there's three ways out of the uncertainty and I'll tick them off if you're ready for those.
Yeah, hit me up. Let's go.
Okay, so the first is plumb the depths of the non-matic markers. Age of onset, family history, course of illness, response to treatment. Dig around in there. So you just need more information. That's the first response to uncertainty. Get more data and use the non-matic markers. I'm going to take a little tangent on that to illustrate the importance of those four. Something that I think you probably know, which is that there is this thing called the bipolarity index.
Gary Sachs from Harvard and some colleagues in the Boston area made this thing up for the StepBD research program. And the bipolarity index says, okay, let's take these five dimensions, symptoms, age of onset, family history, course of illness, response to treatment, and let's give them 20 points each. And make 100 point scale. And then this tool, the Bipolarity Index, has been validated three different times in terms of saying, yeah, this identifies people with bipolar all right, quite well.
But notice what just happened. We gave 80% of the weight to the non-manic markers. Only 20% of the weight went to the symptoms. So plumb the depths of the non-manic markers. There is... Probabilities that you can raise and lower by looking around in there. That's the first response to uncertainty. Are we ready for the next one?
I have a few questions, but let's do these first. Let's do the second one.
Okay. The second one is share your uncertainty with your patient as you do and recruit them to become, recruit them to be part of the bloodhound team. So they're gonna go look around once they know what they're looking for, for mixedness, like four A's, how prominent are those? And any additional bipolarity markers. So they're gonna go look, they're gonna maybe go pursue more information about their family history.
They're gonna think back about, well, before you had that crash in college, Did you have any like depressive episodes prior to that? They can think through that course of illness. Well, yeah, maybe you want to talk with one of your partners or a loved one about like, how bumpy is it for you? Do they think of you as like, you know, what's your mood going to be like today?
Some feedback anyway. So your patient client can become part of the Bloodtown team to go pursue information in these dimensions. And They are motivated to do so by understanding that we're trying to make a treatment decision that carries potential risks for you and we can reduce those risks by improving our degree of certainty. Help me with that. Here, let me teach you about the mood spectrum and let me teach you about mixedness and we can figure it out together.
So the first one was get more data. The second is recruit your client patient to become part of the team, diagnostic team. And maybe some of their significant others as well. And you do this when you're uncertain. If you're fairly certain, you don't have to go through all this, but if your uncertainty is high, the incentives to do all of this become greater. Okay, so that's the second method.
Recruit your patient, client, and there are others necessarily. And then the last one is to simply compare the treatment risks. We don't know. Which path to pursue? So let's look at what are the pros and cons of antidepressants and what are the pros and cons of a couple of mood stabilizer options, including a simplified social rhythm therapy is my number one mood stabilizer and then lamotrigine and low-dose lithium.
So those are the main three that I'm looking at when I'm trying to go, you know, if it was Yeah, so comparing treatment risks. And the reason I like to frame it like that is because if we're really honest about the treatment risks of antidepressants, then the treatment risks of social rhythm therapy Almost none. Lamotrigine, like what other treatment do we have that has no long-term risks if properly managed, including weight gain or any of all the rest of the downsides?
And even maybe some potential withdrawal, but not much compared to antidepressants. And then even low-dose lithium, which we can talk more about. But when you look at the risks on that side compared to antidepressants, including the potential, not just sexual dysfunction and potential for withdrawal, but Potential for making this thing that we don't know worse. Once you have, so you're just sharing with your patient, help me, how does this sound?
We're going to have to think about all these options, whether it's depression plus PTSD, there's a psychotherapy approach, but maybe we were thinking about an antidepressant. So again, it's the antidepressants versus the mood stabilizers comparing the treatment risks. That's the third approach to uncertainty.
This is great. This is so helpful. I really like that you're breaking it up into particular three things that we can really look at. And what stuck out with me is you mentioned if uncertainty is high, that's when you need to really do that investigative work. And what I like about that is in an ideal world, I would call collateral for every single patient. I would call their parents.
I would call their partner. I would call their children. I would get... All the information. We do not live in an ideal world. And I'm sure for the clinicians that are out there listening, they're going, yeah, I would love to call collateral. But I've heard providers seeing like 30 patients in a day, five days, like crazy, crazy things. There are people out there seeing more in a day than I see in a week, which get out of that clinic.
But there's also, I want to be realistic here that not everyone can call collateral for every patient. Yeah. And admittedly, I don't call collateral for every patient. Now, it depends on how uncertain I am. There are some patients that the risks are really high and I need more certainty. And I think with the Lindsay Clancy case, for example, I think the importance of when you're not certain that the stakes are high.
Can I interrupt? Yeah, of course. She should not have been an uncertain case. By the time she got to our third, fourth provider, there was enough data there that the degree of uncertainty for her would not have been very high.
And it's a great point that if you're talking to a patient and they seem dysphoric and they're crying and they're saying thoughts of harming, it warrants calling the previous provider. I'm not going to call the previous provider on, you know, every single previous provider for absolute I did an intake on a patient who's depressed at 22. I'm not going to call his pediatrician from 10 years ago.
But when the stakes are higher, when the symptoms are higher, yeah, we need to be gathering more information and getting more certainty when the stakes are higher and higher.
And sharing that responsibility with one's patient so that it's not all on your shoulders. And I'm thinking about those super busy practitioners that you're referring to. Yeah, okay, so you're not going to be able to make the call today. You send them home with an HDL32 PDF and say, talk about this with your people, and then we'll take her from there when you come back. As long as you are pursuing the information before you set out on your treatment course, I think you're doing the due diligence and you have to split it up into pieces if you're super busy like that.
Absolutely.
I mean, I think it's a great point is having the patient help us with getting that information is super helpful. One thing I wanted to touch on, and so you mentioned the things that point you in the direction of bipolar, and one of those things is course of illness. And I think for the other examples you gave, it's a little more obvious. Like when you say family history, I guess there's some nuance.
If I hear a lot of substance use disorder, it will point me a little bit more into bipolarity as an example of a little bit of nuance. But for course of illness, what are you referring to? What are the things that you hear that you think yes to bipolar, course of illness, or you think... What's a typical course of illness for bipolar?
What are the things you're listening for? Number one is cyclicity, recurrent episodes. Now, people can point back over their shoulder and explain why they think they got depressed. And so it wasn't bipolar. It wasn't cyclicity. It was like that thing that happened in my life. That's why I got depressed. And most people can look over their shoulder and see something bad that just happened. And so there's usually a cause that one could point at for the onset of a depression.
So the one that I like to look at is the offset of the depression. In other words, I'm asking, You know, these depressions that you've had. Have you ever had the experience of going, boom, out of it? Like, just stop. How did that happen? What did I do? I want a bottle of that. I need to be able to use that again. Mysteriously, dramatically, and suddenly improved.
That is a big marker. That's much more reliable than recurrent depressions for which they're, you know, people have horrible lives and can have reasons to be recurrently depressed. But coming suddenly out of one is different. So to me, that helps define this thing as like, it's doing this. It's not doing that. I hope that helps. So cyclicity is the first part of what Defining this, I'm sorry, the nature of the downs and then particularly the ups helps us refine this notion of cyclicity.
You know, you could just be kind of raw about it and go, well, more than three episodes. Which is where the cutoff is in our recommended modifications in the Rapid Mood Screener that there is for your people who haven't seen the Rapid Mood Screener. One of the six questions on that thing is, have you had six or more episodes? That's setting the threshold super high. I think three or more episodes is a more, and research-based, So I'm listening for three or more episodes of depression to simplify it.
That's the frequency part of cyclicity. And then there are two other variables that went into the bipolarity index under that heading. One was postpartum onset of depressions, which is a bipolar marker in the sense that it raises the probability of bipolarity. It doesn't make the diagnosis, it raises the probability. So postpartum onset of a depression. And then the last one that went into that bin is psychosis.
Ever having been psychotic without a substance to account for it is part of the kind of cyclicity. But it's so uncommon and it's going to catch people's attention anyway. If we just drop that one off the list, that's okay with me. And you end up with just like recurring episodes and postpartum onset.
I'm glad you brought up. I've had a lot of patients with mood disorders that they go, it wasn't that because this happened. And I've heard patients justify 15 episodes saying like, no, each one. There was a very particular reason. And what I like to explain to patients is our minds are meaning making machines and our minds automatically find things to cling to to make sense of our experiences.
And you're like I've said. Yep. Now, I actually really liked what you had said about, you know, fast offset from depression. Do you have any other little pearls that don't necessarily say this is definitively bipolar or definitively something else, but little characteristics of the episodes or little things that you hear that suggest something in one or another direction?
Yeah, you remember there were four of them in the old atypical depression. Remember atypical depression, it was characterized because it was more likely to do well on an MAOI than a tricyclic. You're too young for that. But back in the day, that was a distinction that we recognized. And atypical features were increase the probability of a response to MAOI. And what are those? Hypersomnia, sleeping a lot.
Like we're talking a lot, a lot. 12, 14, 16 hours and 24. Hyperphagia, which I think translates to people just... Crave carbohydrates and want to just shout out. It's not just everything. It's carbohydrates in particular, but eating a lot. I'm going to forget. Oh, yeah, yeah. Leaden energy. I particularly like this one. And you nod when you hear it, Dr. Malzberg, because this is maybe what you were hoping I was going to describe.
There is... It is more likely that when someone shows up with this profound lack of energy, that that's a bipolar depression as opposed to unipolar. It raises that probability a little bit. The overlap is too big for it to be very precise. But lead in energy or lead in paralysis, profound lack of energy. One of my patients said, I went to the bathroom. I was headed back to the kitchen.
I got as far as the living room and I lay down on the floor and I couldn't get up. There's something wrong with the mitochondria, and that's probably literally true, but metaphorically, that's what it sounds like. Lead in energy, lead in paralysis, that was the third of those atypical features. And then the last one was rejection hypersensitivity, which is way too overlapping with borderlimity. I don't think really you'd spend too much time trying to sort that one out.
So really what you end up with, because hypersomnia is not all that distinctive. The one of these four things that's really the most distinctive is the energy one, lead and paralysis. So I do listen for that one.
In our last podcast, you dropped the borderlineity. I haven't heard that before, and I love that idea. I think you mentioned essentially spectrumizing the concept of borderline personality disorder. Yeah, I guess I've never heard anyone talk about that. Do you have any more thoughts other than just kind of that general idea of how to think about that?
Yeah, it's easy. Why would we think that there was some sort of threshold or cutoff for this thing? It's a trait. It can be really profound and really mess up people's lives and people can learn how to Combat this trait that they have of rejection, hypersensitivity, for example, overvaluation, devaluation, crisis-oriented thinking. Those are all surmountable with a lot of time and energy and work and help. But why should we think that those things are black and white?
So why not think of it as a spectrum? And once you do, you need a name for it. Let's call it borderlineity. Besides borderline personality disorder is a really bad name. It's required such a pejorative aspect for one thing. And there's also we psychiatrists who are so smack dab normal are going to call you as having a personality disorder. It's not a really good... The optics are not good.
Yeah.
I hope that I see that word pop up more and more because the way the DSM is structured, it's so hard to talk to patients. Patients come in good faith asking, do I have borderline personality disorder? And... When they do meet two or three criteria or the severity is not quite there, calling a personality disorder is a wild thing for some patients. And we can't cram them in a box.
And I feel like the borderline concept would give us a vocabulary for talking to patients that would allow us to say, this isn't a mood disorder. Yes, there's mood swings from what you're describing, but it's not a mood disorder. But also, we don't need to say your personality is entirely broken. And I'm not saying personality disorders. That's the truth. I'm just saying that the implications of saying personality disorder.
Yeah. Any other little nuggets? I feel like this has been pure gold. Any other little nuggets for symptoms of bipolar that you hear, length of episodes, anything in particular?
Yeah, length of episodes, you know, Nasir Gami likes to say, you know, typical duration of a major episode of major depression is more like six months, whereas for bipolar is more like two or three months. I've never found that particularly helpful. Yeah. But yeah, so you're also too young for this and probably most of your listeners, but there was a fellow named Hagapo Kiskal. Dr. Kiskal was really an amazing, brilliant, flamboyant guy.
You'd think that he was so wild, it would surprise everyone to discover that he trained at the NIMH. He was a very rigorous doctor. Capable of being a very rigorous thinker, but he was all over the place. And so he used to say, oh, it's the rule of threes. Three marriages, three languages, three credit card defaults, three college degrees. And so that was the one, the rule of threes.
And then the other one was a woman presents to your office in a red dress. She has bipolar disorder until proven otherwise. He was just, he loved poking people with this stuff. And actually, I'm afraid he helped us in many ways. And then he also set us back because he was freaking people out about overdiagnosis with the way he was throwing this stuff around. And he was the editor of the Journal of Affective Disorders for quite a while.
So he could publish anything he wants in D. And so he published an article about the rule of threes. He might have even done the red dress one. I can't remember. But he gave a lot of talks. But to operationalize all that, that's what's in the hypomania checklist, that HTL32, is all of this flavor of stuff that isn't part of the way we usually, we or anyone else thinks about, like, is this really hypomania or is this just like normal human experience?
Well, it is part of normal human experience unless you see a lot of it. And so I used to have, and I'm gonna try to dig it up and I'll send it to you. A one-page PDF of 32 items on the HCL, because the formal instrument is this multi-page thing you're supposed to go through and check off. But if you can just see all 32 items on one page, and so for those busy clinicians that you're talking about who are seeing like tons of people per day, if you just had a PDF of the HCL 32 and said, take this home and think about this, and let's talk about it when you come back, I think that's a handy tool.
Awesome.
I see we're at the hour mark. This has been spectacular. Is there any other closing remarks, little nuggets, anything else besides a red dress or three credit cards?
Yeah, with your indulgence. Yes, please. Learn how to do simplified social rhythm therapy. You're already doing most of it anyway. You're encouraging people to have a regular bedtime and a regular rise time, but make that part of your standard approach to people with mood disorders. It is a mood stabilizer to help people regularize their circadian rhythm. And it isn't, and many of us clinicians know this from experience, a regular bedtime and a regular rise time, oh, it sounds simple, but it is not easy for people to achieve.
So you can help people get there. And when you're doing that, you're doing social rhythm therapy. You're doing what I think of about as like 80% of what's in the social rhythm therapy workbook. Is just getting that regular bedtime and regular rise time. So I made a video about that, about sleep regularity as a mood stabilizer, as something like that. It's on my YouTube channel. And you can offload that and say, like, go home and watch this thing.
Sleep regularity as a tool. And that's doing social rhythm therapy. Once you have that as a tool, then you're not stuck with this antidepressants versus like antipsychotics. You can go antipsychotics versus social rhythm therapy. Oh man, from a risk benefit point of view, that's a no brainer, right? And then you can look at Lamotrigine in the similar light. And now you're starting to hold your hands like this in that realm of uncertainty.
Spectacular.
I hope we have you on again. What do you feel like we should talk about next time? And I think I'll see if the viewers have anything in particular, but any other hot topics we need to get you back on?
Well, obviously, I'm a big glomotrigine and low-dose lithium fan. I think we talked about those some in our labs go around. And if people find it useful, more detail on how to do simplified social rhythm therapy. So that people who regard themselves as stuck doing pharmacotherapy can incorporate little bits of it all the way along so that you're not just stuck with pills. It really helps justify our existence as psychiatrists when we're not pill pushers.
And I talked about it so much, I think I maybe have some tricks and tools for... Getting really good at doing simplified social rhythm therapy so that you're not having to go, well, there's this workbook, see, and go buy the workbook and work your way and, you know, how many people are actually going to do that? Instead, just making part of your medication management visits to do that.
That would be... That's a territory. Or looking at the rapid mood screener and going, okay, how are you going to build in a systematic information assessment that you get before you sit down with anybody? Maybe you're getting their PHQ-9s now. That's fairly common. But you need a rapid mood screener. Also, you want to use the modified version. Per our article in the Journal of Bipolar Disorders, not the original one.
It's sensitivity is too low. So we can talk about, well, what about screening tools and the flow of diagnosis? But, you know, frankly, we could just go, hey, who'd you see this week? Who was one of your tougher ones? And what was your thinking process? And let's compare notes. We could do it that way.
I love that. Well, we'll have to have you on soon. Thanks so much for coming on. This was a lot of fun. I think it's going to be super helpful for people. And yeah, hopefully we have you back in just a few weeks.
Can I just point out for your listeners, it's good that you're listening to this Dr. Malzberg guy because he's figured out a ton of this stuff. He's asking these questions because he knows what the answer is and he wants me to give you the answer. Gregory, you could do this yourself because it's clear that you've learned a ton. I appreciate being on with you and having a chance to give you my version.
I appreciate this. My mom's going to listen to this. What you're saying is going to make her so happy. I appreciate the kind words. All right. Thank you so much.