Psychiatry & Psychotherapy Podcast - Akathisia

Episode Date: April 8, 2021

In this episode of the podcast, Dr. Michael Cummings, Dr. Annabel Kuhn, and Dr. David Puder discuss akathisia, the horrible and all too common side effect of psychiatric medications. Subsequently, we go through definitions, history, mechanism, how to rate it, and treatment. By listening to this episode, you can earn 1.25 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Hello and welcome to the Psychiatry and Psychotherapy Podcast. I'm here to talk about getting rid of burnout, increasing job satisfaction, and feeling like an expert in what you do. One thing that created a lot of burnout and angst for me was trying to get continued medical education right at the last minute. So why not join the CME membership and do CME while listening to this podcast? Go to Psychiatrypodcast.com, sign up, sign in, take the test, and the certification is emailed to you in seconds. Hi, welcome back to the podcast.

I am joined today with Annabel Cune. and Dr. Michael Cummings. Annabokune was on Disorganized Attachment, and if you listen to this podcast, you know Dr. Cummings and all the psychopharmacology nuggets he's given us over the years. So today we are going to be talking about acesthesia, and I'm excited about this episode

because I feel like this is one of those topics that as mental health professionals, we really need to be aware of. It needs to be kind of like on our mom. mind as we're treating patients, as we're starting medications or stopping medications. And so, yeah, welcome to the podcast. Well, thank you very much. I'm glad to be back.

How about we start with just the general definition, Dr. Cummings. Do you want to sort of break that down? Yes, essentially, acthesia is a syndrome characterized by motor restlessness, particularly in the lower extremities involving discomfort in the, in the muscles often described as an inner sense of jitteriness or tension, an urge to move. It can occur in other body parts, but certainly the lower extremities are the most often involved. Phenotypically, most often what you observe is if people are standing, there's a shifting of weight from one foot to the other. If they are sitting, there is movement of the legs back and

forth or rubbing of the legs. It's very difficult for a person with acathia to sit perfectly still. Yeah. There's that intertension, anxiety, panic, irritability, sometimes anger, sometimes they get more violent, sleeplessness, discomfort on physical examination. You may see them with these sort of irresistible leg movements, difficulty standing or sitting, rubbing or rocking back, forth, grunting or moaning, repetitive movements are seen sometimes. And sometimes they get even suicidal and the level of torture that they're feeling internally gets them to a place of suicidality. Yeah, when I was reading about it, it looks like there's a huge component of subjective inner tension. And it seems like that would be a really difficult thing to experience.

although he was a somewhat criminal individual i've always loved jack abbott's description of essentially this feeling gnawing into one's bones that has a rather graphic sort of description that makes you shudder regarding this syndrome the yeah the quote is these medications attack from so deep the pain grinds into your fiber you with restlessness. Mm-hmm. Yeah, any other historical tidbits you want to throw out there, Dr. Cummings? Yeah, I did want to note that although we associate ectathesia primarily with antipsychotic medications,

this syndrome actually was first described well before medication induced ecthasea. Ladislav Haskovich, a Czech neuropsychiatrist, described. described it in 1901 and two Perkinsonian patients. He literally described it the syndrome as can't sit still or can't sit down because his patients routinely had to stand up and walk to relieve the restlessness they felt in the lower extremities. Yeah, and it can be, the prevalence is a little bit surprising almost, right? It ranges from 8 to 76% of treated patients in this one author said, and sometimes it can be described as, you know, an EPS type of movement disorder, but in fact, it maybe should be considered more of a sensory motor disorder

because of the powerful sensory component, which is defining the characteristics of the condition. In fact, the sensory component may be the primary problem with the motor signs being secondary to restlessness and the need to move. I don't know if you have any thoughts on that. I do. And indeed, I think this is more a sensory motor disorder. And to some extent, I know that the American Association of Neurology has criticized the term extraparaminal syndromes in the sense that they say, well, these are really

very separate syndromes, acute dystonia, Parkinsonism, and ecthesia. and their view really ought not to be lumped together into a single moniker given that they have very different underlying pathophysiology and very different phenotypic presentations. Yeah, and it also seems like different antipsychotics produce different extra-paraminal syndromes. Yes, indeed, and that would agree with the argument that these should not be too tightly lumped together. So Annabelle, what does? don't you take me through the types and characteristics of ecsthesia and kind of the different types?

And then we'll talk about each one, maybe one at a time. Yeah, sure. So acute and sub-acute acetheia is sort of what comes to mind when I think about acetheia, like when I've seen patients. And this is described as being what occurs within a few days. So acute and sub-acute acetheia, the acute acethegia usually occurs within a few days to weeks of starting an antipsychotic medication or increasing the dose.

So during the initial weeks, it's considered acute and then later considered subacute. And usually that responds, like you can treat that pretty rapidly when you take away the offending medication. Before we move on, let's get Dr. Cummings to pipe in if he has anything down here. Yeah, no, I agree very much with your description. this is the easiest to treat the most responsive to either withdrawal or reduction of the offending agent, or if that's not feasible because of clinical concerns, then use of an acetygia mitigating agent is most likely to be effective in the acute population.

Like many syndromes, the longer acathesia is present, the less responsive it becomes. Yeah, and then there's, why don't you tell us about chronic achycheemia? Yeah. Chronic acethesia simply is acethegia that's been there a long time, probably several months or more. And this is separate from tardive acethegia, which we'll talk about in a bit. Yeah, do you appreciate the delineation between the chronic and acute Dr. Cummings? Does that inform anything in your mind? I think it is useful to subdivide these into acute, subacute and chronic in that it alters the degree of responsiveness that you're expecting and treating the disorders. Certainly the response rate to either withdrawal of the offending agent or to treatment with a variety of medications is going to be far lower in the chronic acathia than.

in the acute, and in fact, almost all of the acute presentations of the syndrome will respond, whereas by the time you get into chronic acetheia, you're often looking at very low response rates. Okay, let's talk about withdrawal acesthesia. Sure. So withdrawal acathia or acethegia, it's supposedly indistinguishable from acute acetheia, but this occurs when there's a dosage decrease or like a withdrawal of antipsychotics. And so this can happen when like about two weeks after discontinuing an antipsychotic. And it seems to disappear within about six weeks. Yeah. I've seen also there's other medications that when they're taken off,

they can potentially produce a withdrawal acesia. Dr. Cummings. So do you do you kind of see this as whenever you're getting off of an ACE? agent and you develop this internal restlessness? Is this kind of what we're talking about here? Yes. And indeed, I think what this speaks to that we'll get to a bit later in discussing the underlying pathophysiology is that, you know, because we associate it with dopamine antagonism,

we tend to think of this, oh, it's a loss of dopamine signal. Actually, it's very likely the underlying pathophysiology is much more complicated involving derangements and imbalances between GABA signaling, dopamine signaling, serotonin signaling, and not infrequently noradrenergic signaling as well. In fact, despite having been described now for 120 years, it would be fair to say that we still do not have a complete understanding of the underlying physiology or anatomy of acetheasia. So the next one to talk about is tardive acesthesia.

Annabel, take us, give us some intro on that. Sure. So tar dive acethegia is a later presentation, whereas acute and sub-acute happens within days to weeks after starting an antipsychotic. Tardive acethegia usually occurs very late in the course of treatment, like usually after three or more months. And it can also occur initially. after discontinuation or dose reduction, just like in withdrawal acetheia.

Yeah. Like the other tardive syndromes, this in some way likely represents a loss of neural plasticity and an inability, essentially, of the, in this case, the motor system to reset to baseline because tardive acetheasia may persist for decades after any offending agent is, you know, long gone. Yeah, and it can sometimes be reduced in severity by increasing the antipsychotic dosage. Have you seen that?

Yes. And if you call, that's somewhat parallel to tardive dyskinesia, which at least in the short term, increasing dopamine blockade will decrease tardive dyskidetic movement. So in this case, increasing the antipsychotic may actually decrease the restlessness, albeit get just as in tardive dyskinesia, the syndrome tends to then reassert itself in an even more persistent, stubborn form if the antipsychotic is continued. Again, getting back to the issue that this may represent a loss of neural plasticity that essentially results in a permanent derangement of the balance between different neural signals. It seems very hard to treat. How many

How many people would you say at Patton State Hospital you have with this issue that you're at any given time? Or have you seen it last like 10 years maybe? We have. In fact, we have some patients almost all the time who have this. Fortunately, it's only a few. And it has declined since we've shifted largely from first generation to second generation. Antisicotics, it probably runs right around 1 to 2% of our population. For those in the audience who are not familiar with the California Department of State Hospitals,

we're essentially a 7,000-bed forensic hospital system in which 98% of our patients suffer from chronic, severe psychotic disorders. And Dr. Cummings, if you don't know to date, he is the head of the psychopharmacology consulting team. Is that how you would title yourself? I think that's a fair description. I lead a group of a network, really, of psychopharmacology consultants. Our job is to improve prescribing practices in the state hospital system and to also assist clinicians when they get stuck with some of these incredibly complex treatment-resistant patients. Yeah.

So let's talk about pseudo-acesthesia. and this is a little bit without their maybe reporting the internal restlessness. Annabel, tell me what you found out about this. Yeah, so it seems that this is a term that is used to describe exactly what you said, like objective signs of acetheia without the subjective component. And it seems that there's some controversy about this. It seems like some patients have difficulty express. this sense of inner restlessness and describe it in different ways.

And so it's hard to say for sure if it's truly a pseudo-condition because people experience this discomfort and describe it in many different ways. Yeah, Dr. Cummings, how would you say the controversy is and what side do you side on? My own bias is that this probably is a cathedral because phenotypically, if you look at these people, they look just like the people with acute and subacute acetheia. If they're standing, they will shift weight, they'll pace. If they're sitting, there's chronic foot movement, leg movement, rubbing the legs, rocking. I think these may simply be schizophrenic individuals in which there is either a loss of connection between the discomfort and the affective response to it.

or there is a deficit and cognitive processing of the discomfort. Frankly, which of those is true? I don't know, but I think this is a valid part of acetheia. The other argument in favor of that is it tends to respond to the same treatments to about the same degree as the other forms of acetheia. And Annabel, tell us about the last one. This Bing-Sikard acesia? I don't know, how would you pronounce it?

That would be my best guess as well. But yeah, this is acathesia in the setting of Parkinsonian disorders, like Parkinson's disease or post-encephalytic Parkinsonism. Yeah, in some ways, hearkening all the way back to Haskovic in his original descriptions. Well, let's jump into the causes of aceshesia. We've talked about it a little bit, but let's talk about some of the nuance. So let's start with antipsychotic-induced aceshesia because that's the most common. So first generation causes it more than second generation, as Dr. Cummings has said.

And of the second generation, what would you say are the highest risk medications and the lowest risk medications? The highest risk medications are risperidone and aeropiprizole. The lowest risk medications are things like quitoapine, Iloperidone, and very likely chlozapine belongs in that category as well. Essentially, what you're looking at is those medications that are less robust dopamine antagonists or less tightly bound to dopamine receptors appear to disturb the relevant signal. transduction less than those things like Resperidone, which is a very potent D2 antagonist, roughly 1.6 times as good an antagonist at milligram per milligram as haloperidol.

Or very potent partial agonists, eripurazol having a very high affinity for D2 receptors of 0.3 nanomolar. Okay. Annabel, anything that you found in the studies? Yeah, there was this study from 2015, I believe it was a meta-analysis. And it was comparing lyracidone, xenopine, and arepiprizole. And it said that those three actually had the highest risk of acetheia compared to placebo and other second-generation antipsychotics.

Yeah. So Laracidone 2.7, acetypine 2.2, airpropazol 1.5. And then, yeah, they agreed with Cummings, Closopene, quatyapine as the safest agents. One comment I would make about Larazadone. Interestingly, it's a very high rate of acethesia virtually vanished when they went from recommending that it be given BID. to Q evening. Yeah, and with food, I've heard, do you agree, dinner time with food is even lower's the risk, or what's the...

Well, the optimal way to give lorazidone is 30 minutes after dinner, dinner of at least 350 kilocalories. Like suprasidone, lorazidone requires active transport in order to be absorbed, not having food on board cuts absorption by roughly 50%. giving it at night, and this is true for all of the neurologic syndromes with the antipsychotics, if you can give the drug only at night, the person will have a far lower rate of adverse effects because the peak of the drug occurs during sleep. The basal ganglia and the motor system are part of the reticular activating system

and basically non-responsive during sleep. Oh, very good. Very good. See, all the, I just love the little nuance crystals you put out there. Okay, and what about dose? Is like dose impacting the, because the way that I usually start, let's say, you know, air preprizol is to start at pretty low, like 2.5 for a couple days. I want to see if they're tolerating it at that dose. If they develop aceshesia on that dose, then I know they're going to be much worse on five. Do you have any sense on how fast things are started and how that impacts? A general truism in terms of the brain is the brain is far more tolerant of gradual change than of rapid change. So certainly a lower, slower titration will have a lower prevalence of adverse effects than a more rapid titration of the same drug. Intrida variation also counts.

The more doses a person takes, the more likely they are to have adverse effects. Probably the best illustration of that, for example, with the dopamine antagonists, is if you compare the oral drugs to the long-acting injectable formulation of the very same drug, same molecule, the injectable, of course, provides very flat plasma concentration curves. on average, while it's the same side effect profile, the side effects occur at about half the rate that they do with the same medication given orally. And that's true for acesia as well? Yes.

Oh, wow. So lower and slower or more stable is better in terms of the brain. Very good. Okay, let's talk about antideminergic antimetics, such as, metaclopramide prochlorparazine i've seen it with um with the metaclopramide a couple times we've got been consulted on cnl for these patients and um i've had one other i've one i've had one outpatient who reacts very very poorly to both of these and any antipsychotic she's ever been tried she's definitely developed aceshesia so i've seen this in practice yeah i've also seen it with

compazine of course which is a dopamine antagonist. You know, sometimes our internal medicine friends forget that while it's listed as an anti-emetic, of course the medications don't read the package insert,

and if you block dopamine, you can produce acethesia. I've never seen, there's two other meds, the reciprocine and tetrabenazine. I've never seen those, but those aren't used very often.

Well, yeah, Reserpine has fallen so far out of usage that there's probably not enough usage to have cases. I have seen it occur with tetrabenazine because we have a number of people with Tardiv dyskinesia. And since the newer variants of the VMAT 2 inhibitors are so expensive around $75,000 a year, we still use tetrabenazine in the state hospitals and occasionally not as often as with the antipsychotics we will see acethesia particularly during titration that's helpful okay um let's go to antidepressants andabel tell us what you found on that yeah so it looks like ssr i have more reports of acetheia compared to tricyclic antidepressants or myoIs which was surprising to me because i usually think if SSRI is having the least side effects compared to those others.

Yeah. Any comments on that, Dr. Cummings? Yes. Well, this gets back to what we were talking about with serotonin playing a major role in the modulation of the basal ganglia in this case. There are four major dopamine circuits in the brain. The mesolimbic, which does not have serotonin receptors, but the other three, the tubero infundibular, the nigrostriatal, and the mesocortical all have 5HT2A

receptors on the cell bodies of those dopamine neurons. If those receptors are occupied by serotonin, it decreases dopamine release by anywhere from 30 to 50%. That is, the dopamine signal declines rather dramatically. And, you know, from the standpoint, point of the basal ganglia, that's not really inherently different than blocking post-synaptic receptors and decreasing dopamine signal. Okay, yeah, that makes more sense to me now. That's good. Other medications include anti-epileptics, anticholinergics, calcium channel blockers, lithium, anti-Parkinson's drugs, azithromycin. Any comment on any of those? they all involve indirectly or directly either altering GABA signaling or noropenephrine signaling or dopamine signaling or serotonin signaling so that you're looking at those four transmitter systems largely and what we're finding is that anything that disturbs the balance among this fairly complex interplay of transmitters

can cause acetheia. Have you ever seen it with azithromycin? Yes. Wow. I treated a patient who started taking a Z-PAC for sinusitis. Day two of the Z-Pack, the person could not sit still. They were utterly miserable. It was a wonderful case of, well, not wonderful for them,

but it was a wonderful example of severe acetheasia that was in this case related to an antibiotic. Wow. Luckily, that does not occur very often. If it did, nobody would take a Z-PAC. Yeah. Annabelle, take me through the recreational drugs that do this. Sure.

So, yeah, sympathomimetics can cause acetheia, like methamphetamine, and also cocaine. Gamma, hydroxybuterate, or GHB. has been reported as well as MDMA and ecstasy for causing acethegia. Yeah, again, not surprising because acutely when people take these drugs, the effect on the dopamine system initially is a huge, gigantic increase in dopamine output. It's gigantic to the point, though, that it causes dopamine depletion. So the person goes from an excess of synaptic dopamine to a loss of synaptic. dopamine. And they frankly can look pretty acuthetic both at the peak and then at the

subsequent trough. Yeah, there can also be in withdrawal states, you can have either SSRIs or opiates or benzodiazepines or other drugs. You can have the development of aceshesia. And there was one case that I found of gabapentin withdrawal even. Yes. Oh, and indeed. benzodiazepine withdrawal also can cause acethesia. Again, getting back to the idea that these neurotransmitters are in a very elegant interplay, balanced in a very tight homeostatic range. And anything we do that causes a disturbance of that homeostasis either up or down can then lead to acetheia. there was a i don't know if you heard about this case dr cummings it's a very public case so i don't mind

discussing it here but there was a a canadian psychologist jordan peterson who um was treated with benzodiazepines up to i think four milligrams a day of uh i think it was clonopin or something zanak's a clonopin and when he withdrew from that he developed this internal restlessness and this is what he said. You would not wish that on anyone. It is unbearable, to say the least. People have been driven to suicidality within an hour. And I had this sometimes seven hours a day.

Imagine someone jabbing you really hard in the rib and you want to pull away and there would be a spasm from that and you would want to move because of that. Well, then imagine that is happening 50 times and every time you breathe, that is sort of what it is like. It was just there and it is there. I could not sit down. I've just started being able to sit down in the last month. That was like months and months later after this started.

So it seemed like he had a very prolonged case. Yeah, one of the reasons that if somebody has been taking either high dose, high potency benzodiazepines or very long-term benzodiazepines, it's really important to taper them gradually off of the benzodiazepine. The results of, of course, stopping too quickly can be numerous, including things like seizures. But one of the outcomes can be very vicious, essentially what amounts to a prolonged withdrawal acethesia. And he's right. Among all of the motor syndromes that we talk about,

acethesia is far in a way the most miserable yeah i i think um reading his account it seems like it's even continued to this time he says it's worse in the morning it gets better by two in the afternoon months and months later it's just it's um and i think he's off of everything is what i've heard off of every SSRI every benzo at this point yeah i think it would be fair to say that he went from, he indeed made the transition that we talked about earlier going from a withdrawal acetheia to now a, indeed, a tardive acetheia. And, you know, there are some syndromes in the world that should be on everyone's, I don't want that list. And tardive acetheia is one of them because it is miserable and it is incredibly difficult to treat. Yeah. So that is,

something that we would not wish on anyone. And that's why we're talking about it today so that we can hopefully put it in your mind to screen for this. And we'll get to how to screen pretty soon. So other conditions that worsen egotesthesia, Annabel, any thoughts on that? Yeah. So it looks like renal disease, diabetes, hyperthyroidism, iron deficiency, anemia. And then Parkinson's disease, as well as,

peripheral neuropathy, but I wanted to ask about Parkinson's disease, because earlier we talked about how, like, this Bing-Sikard acetya is, like, the term that describes acetygia in the setting of Parkinson's disease. But, yeah, I wanted to ask if that's, like, a separate entity, or if having Parkinson's at baseline worsens acethesia, or kind of how to think about that. It likely both makes acetheasia more likely, as in the original described cases in 1901, but also likely worsens it as well, because of course in Parkinson's disease, you're looking at the loss of capacity to synthesize dopamine in the substantia nigra and the pars compacta. So in many ways, that naturally occurring pathology was replicated by us much later when we discovered antipsychotic medications, not that the antipsychotics caused these cells to stop making dopamine, but they do decrease dopamine signaling. And of course, Parkinson's disease is the classic example of loss of dopamine signal. Beyond that, although we think about Parkinson's disease primarily in terms of loss of dopamine,

the truth is there is a loss of monoamine synthesis across the board, not to the same extent as dopamine, but in recent decades we've come to appreciate that Parkinson's disease is a more complex neurodegenerative disorder than people originally recognized. So we've talked about this before, but how quickly do you see symptoms? It could be days to weeks of starting pharmacotherapy, but it could be when you increase the dose of the pharmacotherapy. So I always like to keep a timeline in my chart of when I increase doses. And so I can look at that when thinking about if this person's presenting with new anxiety,

okay, when did it start compared to when did they increase the medication? And then chronic ectesthesia or tardive ecthesthesia may present months after initiation or dose increase. And so temporal information is very important when thinking about the diagnosis. Anything you want to add on that, Dr. Cummings? No, I think that's very important. Anyone that you're starting on an antipsychotic should be routinely monitored for the evolution of motor symptoms, including acethesia. you know, well, my own biases are very much that psychiatrists should first be physicians. We should be doing routine exams on our patient.

We should have a blood pressure cuff in our office and a scale in the waiting room, perhaps. And we should be monitoring those physical effects of our treatments that occur. And acathias is certainly one of those. or if you're doing tele psychiatry like I am you know you get them to monitor a lot of those things closely with their primary care doctor or buy a blood pressure cup if that's something you want to monitor closely well certainly for example for many patients these days since there are automated way automated blood pressure cuffs and automated pulse monitors they can report that to you Yep. So one thing I'd like to talk about is how is eathesia different from other forms of EPS? And so how do you differentiate it from, let's say, dystonias, Parkinsonism, Tardive Dyskenesias, Tardive Dystonias, anything you'd like to talk about there, Dr. Cummains?

I tend to think of the dystonia's and DEDA as being primarily a representation of imbalance between acetylcholine signaling and dopamine signaling at the level of the basal ganglia. Of course, it's characterized by sustained contraction of one or more muscle groups. Very often the neck, the jaws, the upper back, Acute dastonia can be very painful, but if you give the person an anticholinergic medication, you can abruptly rescue them from the dystonia, suggesting that this in some ways is a much simpler imbalance to correct than acethesia is. Parkinsonism is, again, loss of dopamine signal. In this case, with some changes in loss of plasticity that leads to,

to both braticanesia and inability to move or initiate movement, but also over time, usually emergence of things like resting tremor and other involuntary movements that are involved in Parkinsonism, essentially mimicking the characteristics of Parkinson's disease, usually initially treated with either withdrawal of the offending agent or treatment with amantadine to increase dopamine signal and for acute rescue anticholinergics, although given the risks of anticholinergic medications, we really try to discourage people from routine use of anticholinergics because of their risks of causing cognitive impairment, memory impairment, blurred vision, decreases in GI motility, up to an including bowel obstruction and urinary retention.

And long-term increased risk of dementia. Yes. It's like, please, guys, watch that. Yeah, if you have somebody who is suffering an episode of acute dystonia, by all means, give them an intramuscular or intravenous dose of diphtromine or benzthropine. Don't, however, leave somebody on benstropine for decades when they had one episode of dystonia. I've actually run in cases like that where the person was started on Benstropine when they were 20. They're now 50. They've been on this for 30 years. They've had one

episode of EPS. Yeah, I saw that a lot too, and it's like, okay, I'm going to get off, I'm going to take this off, but get them off slowly. So if they're on like one, twice a day, I'll take them down like 0.5 at a, you know, wait a couple weeks, take them down another 0.5. And the parents, you know, are often bringing in this kid and they're like, oh, he's starting to kind of wake up during the day. It'll be a little bit more active. Yeah. Yes.

You know, three months after an acute episode of dystonia, around 70% of people can be tapered off of an anticholinergic with no recurrence of the acute dystonia. So we really don't need to be continuing this for years and years. And in fact, it has turned out, that the antiviral amantidine is a much better chronic treatment to prevent Parkinsonism and dystonia than are the anticholinergics. Very good. Okay, let's talk about the mechanism of action. There's a couple neurotransmitters that we want to look at, norapinephrine, increased,

serotonin, normal or increased, dopamine decreased or abnormally increased, Hesetocoline, normal or unstable, gabapentin, normal or decreased, and glutamate, normal or unstable. That's from your PowerPoint. Anything you want to add on that? The point in making that slide, this was for a presentation I did a couple of years ago,

was to point out that, one, the neurotransmitter involvement in acetheia is complex, and that, again, it gets back to the idea of things being outside of homeostasis, but not necessarily in a unitary direction. You know, you can get, you see both increases and decreases in some neurotransmitters or simply a neurotransmitter being unstable contributing to the pathophysiology. Yeah, and there's different brain structures where this is involved, the ventral tegmentum, brain stem, basal ganglia, accessory, motor cortex.

Yes. I think sometimes we don't stop and appreciate just how complicated our motor system is. Certainly from the bet cells down to the spinal cord is a fairly simple circuit. But that circuit is modified by input from all of these other structures feeding from the brainstems through the basal ganglia up to the accessory motor cortex. And that's really what permits us to make smooth movements, to initiate movement in a very controlled, fine manner. And that's what we see in these syndromes

is that the person's ability to modulate their starting and stopping of movement has become impaired. So the next thing we want to talk about is how is a anesthesia formally tested? And I think it's, I wanted to go through this kind of slowly, and talk about each symptom and things that we might look for and the different degrees. I think this is going to be really helpful for those of us who are in the trenches, kind of how do we think through what we're looking for? So Annabel, why don't you take us through a little bit on this and then I'll jump in.

Sounds good. So all extra pyramidal symptoms can be tested using the extra paramal symptom rating scale or the ESRS, which was developed in 1979. But if you're looking specifically for signs of acetheia, it'd be useful to use the Barnes Acetheia Rating Scale, which was made 10 years later in 1989. So I think it might be useful to go through the Barnes Acetheia rating scale. Yeah, let's do that.

Let's focus on that. So interestingly, there's two components of it. There's the objective and the subjective component. that are both, like, weighted equally because the objective motor movements that are occurring are as important as the patient's subjective experience and their awareness of this restlessness. So in order to take a look at this scale, the patient should be observed while they're seated, and then standing while they're engaged in neutral conversation for a minimum of two minutes in each position. and so symptoms are observed in other situations too.

So like while they're engaged in activity on the ward, that can also be rated. And then the subjective phenomena should be elicited by the direct questioning with the patient. Yeah, let's go through and let's go through the numbers for the objective. Just maybe say what the number is and this is like, you know, the higher the number total, the higher, the level of ectesia. So let's go through the numbers to kind of show the progression of how this goes. Sure. Sure.

So on the objective side of things, the patient would score zero if there's, if it's normal, occasional fidgety movements of the limbs. And then they would score a one if there's presence of characteristic restless movements, such as shuffling or tramping movements of the legs or feet. feet or swinging of one leg while sitting and or rocking from foot to foot or walking on the spot when standing. But movements present for less than half of the time that they're observed. And then it would be scored two if what I just described are present for at least half of the

conversation. And then a score of three would be if the patient is constantly engaged in these characteristic restless movements and or if they have the inability to remain seated or standing without walking or pacing during the entire time. Yeah, Dr. Cummins, any reflections on those, the objective? One of the things I always do with patients, if I'm suspecting, well, essentially if I'm trying to decide are they a two or a three on the objective scale, is I will actually We ask them to sit perfectly still and silent for a period of two minutes.

People who are three cannot do that. They will make it to about 45 seconds, and then they literally begin to look as if they're going to explode. And usually when they hit about a minute, something will begin to move. Because by that point, the distress has built to the point they can't stand it. and they get a three. I actually had a quick question about the objectivity section of this too, because I was reading and it looks like there's, it's not necessarily always the legs that experience this restlessness.

And so there's some discussion about whether this scale gives too much emphasis on observing the patient's legs, whereas some people might have acetheia involving their arms or their trunk or head. I think that's a correct observation. You know, the emphasis for ectecia has always been on the legs because that's how it was originally described. And that is the most common presentation, but it certainly is not the only presentation. Most people I know who use this scale elegantly, if they have a patient and they know that their acathias primarily in their head or their arms, they will move their scoring, if you will, to look at those other areas.

So just to be clear, Dr. Cummings, you're saying a three cannot stop themselves from moving, like no matter how hard they try. No. No, they will begin to look incredibly miserable. Okay. And I have, well, there's probably somebody out there somewhere that can do it. But I, in my career, I've never met somebody who deserved a three who can get past about 60 seconds of sitting. still. Yeah, because it was interesting when I was

listening to this Jordan Peterson interview. He was talking about at times he felt like he couldn't stop it, but later on now, it seems like he can kind of hold it together for periods of time, but it's really hard to hold it together for long periods of time.

Yeah, he might have declined from a three to a two with improvement over time. And that's, on a practical scale, that's if I'm working with a particular patient and my underlying interest is, are they getting better or are they not getting better? And that's, for me, that's always been a useful signpost that if they can go from not being able to sit still at all for two minutes to finally get into the point where their period is getting longer and longer and they can finally make it to two minutes, that suggests that they're improving in response to treatment. Okay. Let's move to the subjective part.

Sure. So this is the awareness of restlessness. So Annabel, take us through those. Sure. So, yeah, there's like two components for the subjective rating. So yeah, like you said, there's awareness of restlessness. And then the scale also rates distress related to the restlessness, which is an interesting distinction. But so for the awareness of restlessness, a patient.

would score zero if there's absence of inner restlessness or a one if there's a non-specific sense of inner restlessness. A two would be if the patient is aware of an inability to keep the legs still or a desire to move the legs and or if they complain of inner restlessness that's aggravated specifically by being required to sit still. And a three would be if the patient has an awareness of this intense compulsion to move most of the time, or if they report a strong desire to walk or pace most of the time. Okay. And then the distress would be related or rated as zero is no distress.

One is mild, two, moderate, and three severe. The distress related to the restlessness. Right. Yeah. Yeah. Okay. Yeah. So you can see how the misery level is subsequently increased as we go to from one to two to three.

I like to catch people around one, you know, ideally. And so this is where if you ask the question with every patient you start on medication, do you have any internal restlessness? Do you have any anxious feelings that are new? You know, those are very important questions. Dr. Cummings, any thoughts on the subjective? portion? Yeah, I would just encourage people that this is one of the reasons for using a rating scale like this is to remind us to ask those questions because many of our patients are reticent

to complain. And consequently, if we don't ask directly, they won't say anything. Yep. So we need to ask. And I'm hoping that you, listener, will start to ask these questions. and you will catch them some of this, and that will be exciting because you'll be helping your clients. There's a, in the KD trial, it was what, 30% of noncompliance or 30% were compliant with medication, right? Somewhere around there. Yes, yes. So think about those 70% that were not compliant. What percentage of those had these symptoms?

And we're just like, forget this. These meds are making me worse. These meds are driving me, you know, crazy. And so, you know, if our patients say these meds are driving me crazy, maybe it's like, hey, what does that mean? Let's talk about this. Let's see if some of the side effects are actually making things worse. Okay, let's talk about the global clinical assessment of acesia. This is part of this Barnes Acesthesia rating scale. I'll put all these notes in the handout, in the PDF that'll go with this. So you can check this out. Annabelle, you want to take us through this a little? yeah sure so if I'm not mistaken is this where you add the score up

and then like whatever you add it up to you can like rate it based on these yes this is sort of this part is essentially you as the clinician having gotten the answers to the first three items you're now making a global impression rating

about how severe is this person's acetheisha? Gotcha. So if the patient scored zero for both parts of the subjective and in the objective component, then acethesia is considered to be absent and there's like no evidence of awareness, of restlessness. And there's no characteristic movement seen on exam either. And then it also says, yeah, it says observation of characteristic movements.

In the absence of subjective report of inter-wrestlessness should be classified as pseudo-acetheia. Yeah, number one, so if they scored one point total, it's questionable, non-specific inner tension or fidgety movements. Two is mild acesia, so this is awareness of the restlessness in the legs and inner restlessness worse. When required to stand still, fidgety movements are present, but characteristic, restless movements of ekeesthesia not necessarily observed. And so the condition causes little or no distress. That's mild ectesthesia. Moderate ectesthesia is awareness of the restlessness as described for mild acesia above combined with this characteristic restless movement such as rocking from foot to foot when standing. The patient will find this condition distressing. And then you have a

marked ecsthesia where it includes a compulsive desire to walk or pace. However, they can remain seated for at least five minutes and the condition is obviously distressing. And then severe ecsthesia is when they're pacing up and down most of the time, unable to sit or lie down for a few minutes, constant restlessness, which is associated with an intense distress and insomnia. And This is severely distressing, and this is where they might have suicidal thoughts or angry thoughts. Yeah. Any coming to want to jump in at all and say anything about these? Yeah, I just wanted to say that this is a very valuable sort of summary rating in which the clinician can add the other components from their knowledge of this particular patient.

And patients cover a spectrum in terms of their willingness to complain. This in some ways gives the clinician an independent opportunity to say, well, this person is maybe a little worse than they're saying. And you can actually rate them higher if you feel that's appropriate. For example, I've actually had one or two patients who clearly could not sit still, were obviously miserable. But they're, oh, I'm just fine, Doc. you know well no they weren't yeah you know and and patients want to say they're fine for different reasons to you know if they if they think that you want them to be fine and that you're going to like them more if they say they're fine then they may say they're fine when they're not fine

or i've seen a lot of patients they want to report improvement because you know that'll make you feel good as the doctor to think that there's improvement going on um so yeah we need to look for these objective measures of symptoms as well. So why is this underdiagnosed? That's like kind of the one of the questions we were looking at, Annabelle and myself in preparing for this. And Annabel, what did you find? Give me the brief summary of why this is underdiagnosed.

Sure. So it seems like there's two major problems leading to underdiagnosis. The first one being that symptoms, that fulfill diagnostic criteria for acetheasia are sometimes overlooked. And also conditions that do not fulfill the full diagnostic criteria but can still benefit from anti-acathia measures are underdiagnosed. Yeah. Yeah.

So I think, you know, like we said before, people often don't ask the questions. People think that they're just anxious, maybe their general anxiety. disorder, maybe they get a misdiagnosis of some anxiety disorder, or maybe they get misdiagnosed with peripheral neuropathy or restless leg syndrome. Whereas, you know, if we did this, this Barnes Acesthesia rating scale, we'd see like, oh, they have a bunch of these put together and it's leaning more towards this. Any thoughts on this, Dr. Cummings? Yeah, I think this falls into, uh, Well, something that has become true of modern medicine, including psychiatry, is people are often very busy, very rushed,

and don't have adequate time to really assess their patients. I think I was reading one issue regarding managed care, and on average, the time spent assessing the patient is now down to less than an average of three minutes per visit. Oh, dear Lord. So that's like, well, dear patient tell me, in 30 seconds, tell me your relevant history, which is a bit unrealistic. And, you know, that does lead to a lot of things being missed. I know that, you know, the common abbreviation used in medicine for within normal language is WNL. I think however, unfortunately, it can also stand for we never looked.

Yeah, and I think that's a it's a challenge for us as providers to not work in a situation where we feel like we wouldn't be able to do the level of care we think is necessary to do good care. Or kind of, I think collectively we need to rebel against this shorter and shorter amount of time they want us to see patients in somehow. I don't know. I think that's a bigger, that's a bigger issue. I imagine if you're listening to this. I have some psychiatrists because I do coaching now. Reach out to me or are just very unhappy in their situation that they're in. And I get it.

It's like sometimes there's a lot of pressures to see more people. You know, there's a lot of pressures that are driving people to these shorter visits. But it's not always what's best for unnecessary. Cummings, any more thoughts on that? Well, I agree with you. I think this is a case where we have to be sure that as physicians, we remain in charge of the patient's care and treatment. Because in many ways, we are responsible for our care of the patient,

and we can't allow ourselves to be too pushed, to essentially do shoddy work. Yeah. I recently worked with one provider who was at an outpatient practice, and they were unable to schedule someone for a follow-up, except for like four months out. And we talked about not accepting any new patients for a while. Well, that wasn't the policy of the place.

And so we talked about how to have a voice, how to have the ability to sort of negotiate with the place they were at. And they were able to successfully get heard, and they made changes where now they're able to, you know, see patients one month after, if they want because they were able to set their clinic up. And I think it's really important for us to realize that the people making the decision sometimes are not thinking about what's in the best interest of the patient.

And we are the patient's advocates. So let's keep going. What are some consequences of undiagnosed and untreated acesia? So this is kind of venturing into the more difficult aspects of psychiatry, I would say is seeing that, yes, sometimes our medications can cause harm to people. People can be more violent on these medications at times and more suicidal. So Dr. Cummings, what do you think about ecesthesia and suicide? What have you seen from the literature? It certainly carries a substantial risk of inducing suicidal ideation, particularly when you get up into severe acethesia. It is such a

miserable condition to suffer from. I think this is another call for us to recognize acethesia early, because again, the important thing is that acethesia in its early acute stages is highly treatable as opposed to its late chronic or tardive stages where it's incredibly resistant to treatment. We need to have this, as you suggested at the beginning, in the back. of our mind and if someone, for example, is being treated for psychosis and you increase their antipsychotic and they become more restless, more violent, more threatening, the thing that should cross your mind is, could this be acetheia? Or if the person says you started me on this

med and now I have these incredible anxious feelings, again, the thought should cross your mind, is this acethesia? If I push harder, am I going to make this person suicidal? Yeah, I've seen this specifically with autism. Patients get put on risperol. One patient got put on Prozac as well. That increased the risperdal dose substantially because of the 2D6 being blocked by the fluoxetine. And it increased the risperal dose and the patient develops aceshesia and gets more aggressive. And it's like very hard for someone with autism who's nonverbal to express that. But I could feel it in my office.

I could literally feel this like intertension. And you could watch them fidgety and moving around, you know. I do have to say one of the things you'll find if you interview very many acathetic patients when you're sitting across from them and they can't sit still, they're fidgeting, they're rocking, they're shuffling their feet, you'll start to find that you're having a hard time staying still as well. Oh, absolutely. That's actually how I identify it as someone who's, you know, maybe more empathic and someone who reads my countertransference. My countertransference to these patients is like, I feel like I want to jump out of my skin. And it's just like right there, right away. It's like, wow, why do I feel like I just want to like move around? And so if you have attunement to your own empathic experience, I think, you'll feel that and it's very distressing.

Very distressing. The study in particular that I looked at showed that suicidal ideation was associated with observed aceshesia in first episode schizophrenia patients who were treated with halidol or risperdoll. And this was a study of 289 patients. Interestingly, I also found a study where older patients treated they did not have an association between ekeesthesia and suicidality. So there's a thought that maybe it's like in this sort of newer schizophrenia diagnosis,

newer psychotic diagnosis, there was increased risk between these two things. Any thoughts on that? I think, you know, when schizophrenia is new, you know, it's certainly a horrible disease. And I think something that we don't appreciate, you know, if you say major depression, people think, oh, suicide risk. The suicide rate among people with schizophrenia is actually higher than among people with major depression. Not only are these individuals going through incredibly difficult changes in their thinking, their perception of the world, but if we add to that, a very distressing sensory motor syndrome, it makes sense

that it is going to be very difficult for them to deal with. I think in the the older schizophrenic patient, they've often adapted to some extent to having a chronic psychosis and are more tolerant of many adverse effects than a younger patient is. I have heard of this interesting case where our patient was, he was admitted to the inpatient unit and was complaining of a tremor and was admitted because he, well, he was on flu, which was prescribed a few months prior. And he was completing of this tremor that made him want to cut his arm off and die by suicide. And it was interesting because there weren't any other signs of acetheia, but it looks like acetheia is the only extraperiminal symptom associated with suicidality.

So interesting case there. Yeah. Yeah. Indeed, Annabel. If you have a patient who says, I have this movement symptom. Well, if that's all they say, then you're probably not looking at acathia. You're probably looking at a dystonic tremor or some other motor symptoms. But if they say this thing is moving, whether it be their leg or their foot or their hand,

and it's driving me crazy and I would rather die than have this continue, you're likely looking at acathesis in some form. I want to talk about acesia and how it increases. aggression can increase homicide risk. This seems to be a pretty triggering topic to even think about for us as providers that we would give something that would increase someone's aggression, increase their risk of killing someone else. I found this case study of 10 patients who had attempted or completed suicide homicide who were found to have these P450 mutations that might have increased the dose of the medications that were given and caused aceshesia. This is Lucre

2011. Are you aware of this study, Dr. Cummings? Yes, I am. Is this study like, does it have holes in it? I mean, there's a lot of details in it. I'm just wondering as a forensic psychiatrist, if you look at this and you're like, yes or no, or like how you view this. I think, you know, some of the details may or may not be correct, because so far this has not been replicated. However, I think the general observation that acethesia can drive not only suicidality, but increased violence, is definitely valid because that has been replicated in the form of a variety of correlation studies. And in some ways, it's not surprising. If somebody is suffering from a condition that makes them physically miserable, if they are

all prone to aggression, loss of impulse control, making them increasingly miserable, certainly does not help limit their probability of becoming violent. So the study really pointed out there's issues in like 2D6 that lead to, you know, increase in the nortriptylene or Paxil or Prozac, you know, that are broken down by 2D6. they describe case study after case study of this occurring. And when I'm reading some of these case studies, it almost looks like some of them were more delirium or like the confusion level or the lack of memory of what happened

was there were some gaps in memory. And so one of my thoughts and questions for you is like, okay, so is he describing aceshesia or delirium in some of these clients, you know, who had very, anticholinergic medications as well that were obviously very much high in the level, potentially due to the mutations due to not having these genes? The answer is it may be both. Certainly for anticholinergic medications, those impair cognition and memory.

But ramping someone's affect is stayed up to the point where they become overtly violent also tends to impair memory function outside of people with mental disorder if you do a survey of people who've committed very violent crimes and ask them to give you a detailed timeline of the crime. Only about a third of people who've committed violent crimes can actually give you an accurate timeline. When they are very effectively aroused, people don't require. cord and consolidate memory accurately. Interesting. And for some of these individuals who are already suffering from a psychotic disorder,

meaning their thinking may not be all that organized to begin with, if we do something to them that makes them more miserable to the point of becoming affectively aroused and violent, in some ways it would not be surprising if their memory of that event is less than crystal clear. Okay. So let's talk a little bit about similar or linked pathologies. And I know you had mentioned before Restless Leg. I wanted to get your take on this. Is it similar in how they both have increased tension, anxiety, restlessness? Is it the same thing going on? And how do you differentiate them in your mind? Similar and different. Things that are different that can help distinguish them because that's

often clinically what we're interested in doing. Acethesia occurs about equally in men and women. Ressal-Slegg syndrome is somewhat more common in women. Ressless-sex syndrome is also more common with advancing age, things like iron deficiency, for example. Rustless leg syndrome presents with paristhesias, which acethesia does not. And probably the most telling thing about Restless Slick syndrome is that it is almost always in the evening and then tends to resolve

during the daytime, whereas, of course, acetheia can be much more 24-7. So there are some important phenotypic differences. In terms of the pathophysiology, they are probably somewhat different but related in that

we only have a certain number of neurotransmitters involved, in the ventral tegmentum and basal ganglia. In the case of restless leg syndrome, we're probably more purely looking at either things like iron deficiency, which alters basal ganglia functioning, or things like dopamine deficit, because indeed one of the key treatments for restless leg syndrome, of course, is a dopamine agonist at bedtime. Okay. Yeah, those are helpful. And we'll have more notes on this in the handout, getting to the treatments that are supported by evidence. So once you have decided through, you know, testing and observation that this person has aceshesia, the first thing

I think about is decreasing the offending agent. So thinking about historically what happened, reducing the dose. And I also think about like, okay, how do I acutely, if they have very high symptoms, how do I acutely make them feel better? Beta blockers like propanol, 40 to 80 milligrams a day, mertazepine, 15 milligrams a day. Now you taught me that a couple years ago when you were on, and it's been very helpful. And actually I had one patient who,

when I tried to take him off of mertazepine, he got restless. So I think it was actually protecting him, some of that underneath. And then those are the main ones I think about, propanol or mertazepine, of benzodiazepine, like a long-acting one, lorazepam, clonazepam, diazepam. Yeah, indeed, the data in terms of the amount of data that's available is best for the beta blockers, propranol being the most common.

Metoprolol, less data, but it does appear to be effective. Mertazepine actually is more effective than the beta blockers at 15 milligrams at night. that's the only dose that's been tested, probably due to its ability to block 5HT2A receptors. Also in that same vein, things that block serotonin signaling, meanserin 15 milligrams, or cyproheptidine, 8 to 16 milligrams, have also, in much smaller data sets have been shown to be useful. Yeah, there's a couple, it seems to be emerging medications for acesheasies. and acetylcystine. It was one four-week study that compared 140 patients with schizophrenia.

They had 84 completers with one gram twice a day of an acetyl cysteine versus placebo. And there was a moderate reduction in acesia with an acetylcystine. Any thoughts on that being an option? It appears to be functioning as an antioxidant and may be protective over the longer term. The effect, as in the study you described, was not as acute as with either beta blockers or serotonin blockers. It was a more sustained, gradual effect. So, you know, in acetylcysteine could possibly be a protective agent in some patients. Say you have somebody who clearly is sensitive to developing acetheia, you're going to have to put them on an antipsychotic long-term.

Nacetyl cysteine might be a way to protect them as they're taking the antipsychotic. Same thing might be true, a very high-dose vitamin B-6, which also has very modest data to suggest that it reduces the prevalence of acetheia. And then we also have data from some non-benzodiazepine GABA urgic agents, things like gabapentin, which of course is FDA approved for a restless leg syndrome, will not

surprisingly, it also has shown some efficacy in treating acethecia as has pre-gabalin. Okay, very good. Well, this is coming to the end of our time and I just want to maybe

give a moment to have any final remarks. my final remark would be please screen your patients for restlessness at least asking them since you know since have you been feeling restless have you felt and you know the second question if they said yes does it help to walk around or do you feel like you're moving around more and then if they're restless looking and they might report restlessness either one of those going through the barns aceshesia rating scale is, I think, very important. And so once you have that diagnosis,

then think about when it started, so what type it is, and what was the probably most likely offending agent? Can you decrease that agent? Can you switch to another agent? So, for example, if they're on a risperdol or something like that, could you switch to Cerequil,

clausero, or Cyprexa? Would you put Zyprex in there, Dr. Cummings? Yes, I would. In that category? Okay. And, you know, could you switch them? Could you decrease them? Could you add a propanol to, you know, decrease their just tension in the moment?

They're, you know, do they have such severe symptoms that they need a benzodiazepine? One patient in my partial program when I saw her, it was so bad that I immediately said, go to the pharmacy right now, pick up Clonopin, take it today. It was that bad, you know? Do not wait till the end of this eight-hour group therapy. Go right now. So the urgency on this is pretty high. And then see them frequently.

You need to see these people, you know, multiple times a week sometimes just to make sure this is being improved. The other final pearl that I would put out there is after you start a patient on a medication, they need to be able to feel like they can get a hold of you. So this is like the one thing that I warn patients on when I start them on any medication. Like, hey, if you feel more restless, please reach out to me sooner than later. You know, I don't mind an email.

I don't mind a phone call. You know, and please reach out to me because we need to talk about it, you know, and get them in that day and talk to them for five minutes or ten minutes and figure out what's going on. So those would be my sort of close remarks. Annabel, do you have any? I think, yeah, after looking at all the information, it's really important to catch this early, like you said, and consider it every time you're starting an antipsychotic or increasing the dose. Okay, here's my question for you, Annabel,

okay? Yeah. You're at Harvard. You see that a person has aceshesia, and you bring it to your attending, and your attending shoots it down and wants to increase the antipsychotic. What do you do next? I would ask them why do they think it's not acethegia. I've been primarily. I've been practicing for 10 years, Annabelle, and I know that this is not ecsthesia. This is anxiety. They need this antipsychotic. I think at that point, I'd probably, you know, print out the barns acetheia scale and say maybe let's take a closer look at it and really, really kind of press that. I'm definitely not shy to stand up for what I'm thinking. And maybe I am wrong too. But it would definitely be interesting and important for me to explore that and challenge that. Yeah.

Yeah, no, I was going to say, because I know that there's people who are listening to me who have emailed me, and they are not, they're like a psych nurse. They're like, how do I communicate this with the attending, you know, or one person was even just working in a psych hospital. They weren't, they didn't have like a title, you know, like a nurse or a physician, but they were catching people with this issue. and I said, call the attending, talk to them. But I think that when I was thinking about this right now, print out the Barnes' ecesthesia scale, circle what you see, and then bring that to the person in authority, hand that to them and say, hey, here's what I see with this person. I'm new to this. Hey, help me understand what's going on. I think that they just started this medication.

Could it be from this? I'm worried that they might have this really severe restlessness. I don't know. Dr. Cummings, any thoughts? Yeah, I think those are definitely worthwhile. The other thing I would add as a closing comment is for any of our clinicians, if you start a medication that can cause acethesia, which we've gone over those during this hour,

the antipsychotics being the primary group, but also SSRIs and some others like calcium channel blockers, some antibiotics. And the person appears restless. You should do two things. One, review the person's medication list and be sure that you're not giving them a drug that inhibits the metabolism of the newly introduced drug. And two, consider obtaining a plasma concentration of the potential offending agent. You may be looking at a much higher plasma concentration than you expected. There are people who are very poor metabolizers for a whole variety of drugs. And consequently, you may be seeing this as an adverse effect, even though you're thinking,

well, it couldn't be the dose is so low. Something I've said before on this program is dose is a very, very poor guide to the adequacy of treatment. If you're in doubt at all, get a plasma concentration. Yeah, 100%. But I would also add, Dr. Cummings, how long do you wait for that plasma concentration to come until you take action if someone is in the more severe range? Oh, you take action immediately. The lab, as most labs are, is simply confirmatory.

I personally am very much opposed to people practicing by laboratory data. The purpose of most labs is to confirm what you already know clinically. One of my criticisms of current medicine is too many of us and our colleagues have become overly dependent on lab data. If you have an abnormal lab in your hand, the first thing you should do is go look at the patient. Yep. Very, very good. I run this program for people with medical and psychiatric issues in California still. and one of the patients recently came with severe anxiety after the tidal volume was dropped. She is on a chronic trache. I corresponded with the physician who had been treating to her ABG and not her subjective symptoms.

And one thing that we know from like yoga breathing or relaxation breathing is that big tidal volume breaths are actually very calming. And short title volume breaths can be anxiety provoking. And so I provided some articles and evidence for that. And she actually took my evidence and it cured the issue. But I think it's just a testament to that. Like the subjective experience of the history taking and our knowledge is very, very important. Labs, I like how you said it, they can confirm, but shouldn't guide necessarily us. Unless, you know, obviously if they're hyperthyroid and they're.

T4 and T3 are way, way high. It's like, yes, of course, that needs to guide what we do. Any other thoughts on that, Dr. Cummings? No, I think that pretty much does it for me. Okay, well, thank you so much, Dr. Cummings, Annabelle, for helping me put this together. I think that the people who listen to this are really appreciative, so I'm appreciative of your time and effort, and we'll get this out there soon. And, yeah, we'll leave it there.

Okay, great.