Psychiatry & Psychotherapy Podcast - How to treat violent and aggressive patients

Episode Date: January 23, 2019

The words "aggression" and "violence" are sometimes used synonymously, but in reality, aggression can be physical or non-physical, and directed either against others or oneself. Violence is more of a use of force with an intent to inflict damage. One study looked at the principle types of aggression and violence that occur in psychiatric patients, and broke it down into three categories: Impulsive violence (the most common category) Predatory violence (purposeful and planned violence) Psychotically-driven violence (least common) By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video. Instagram: dr.davidpuder Twitter: @DavidPuder Facebook:DrDavidPuder

Welcome to the Psychiatry and Psychotherapy Podcast, the podcast to help you in your journey towards becoming a wise, empathic, genuine, and connected mental health professional. I'm your host, Dr. David Puter, a psychiatrist who splits his time practicing psychopharmacology, individual and group psychotherapy, medical director of a day treatment program, medical education research, and teaching, residents, and medical students. Okay, welcome back to the podcast. I'm here with Dr. Michael Cummings. he's been with us before and today we are going to be talking about violence and aggression dr cummings welcome to the podcast thank you very much i'm happy to be back um as many of your

listeners know i work at a state psychiatric hospital for the criminally insane so indeed treatment of aggression and violence uh is pretty much our daily bread and butter so in this episode we're going to be hoping to go through some of the definitions of violence and aggression, what causes it, how to identify it, how to treat it. And so, yeah, let's start with maybe definitions of how you would define different types of aggression. Okay. Well, first, aggression and violence, although they're all sometimes used synonymously,

aggression can be physical or non-physical directed against either others or oneself, whereas violence more often denotes use of force with an intent to inflict damage or injury. In considering violent behavior, a study that came out of New York, about a decade ago now, looked at the issue of violence in psychiatric patients. The authors were agnostic regarding diagnosis and just looked at the principal types of aggression and violence that occur in psychiatric patients. And they've basically found that it broke down into three categories. There was impulsive violence, which was the most common category.

then there was predatory violence that is instrumental or purposeful violence. And then lastly, in a chronic population, psychotically driven violence, was actually the least common. That was replicated in the California Department of State Hospitals when we looked at 88 of our chronically or persistently violent patients. the rate of impulsive violence was 54%, predatory violence was 29%, and psychotically driven violence was 17%. That's very different than people who are acutely hospitalized. When we first get patients, at least during the first two or three weeks, psychotically driven violence is often the most common.

Yeah, so I think it might be good to define. what's sort of behind each one of those types. So tell me a little bit about predatory violence. Okay, predatory violence is what people typically think of in association with psychopathy or with antisocial personality disorder. This is a non-effectively aroused form of violence. The person looks to have a gain from being violent. They can dominate others.

They can obtain property. Essentially, this is violence for a purpose. Probably the animal analogy would be the typical cat hunting mice. The cat's intent, focused, not excited, and is essentially about to be violent as a means of getting food. Yeah, so this is the cold-blooded killer, the calculated personality in various videos, movies that come to my mind where it doesn't seem like he's extremely angry, but planning, scheming. What types of brain centers are activated for this type of person? This type of person shows a lack of fear.

And indeed, as you would expect, that means that the amygdoll. which is a complex of neurons in the temporal lobe is underactive and indeed the communication of the temporal lobe which does emotional processing its connection to the the frontal cortex via the unsinate vesiculus is impaired the signal is weak and consequently these people tend to be somewhat emotionless they often show very little autonomic arousal, even when being violent, and often have a very hard time identifying or empathizing with victims, such that from an emotional standpoint, they don't distinguish much between ordinary activities and inflicting harm on others.

Yeah, I was just going through a study for the most recent episode. on empathy and primary psychopathy this cold-blooded you know low physiologic arousal type of personality has um low affective empathy specifically and um they can have normal cognitive empathy meaning they can kind of guess what you're thinking and and put words to it but they won't be able to feel it there they won't be able to like resonate with the emotion yes uh very much so and indeed some of the early research done in that area by adrian and reigned from, well, he was then at USC, in Mauritius, found that he, by measuring blood pressure, galvanic skin response, and heart rate, when showing children at 3, 5, and 8

years of age, pictures that were either neutral or frightening or peaceful, those who lacked an affective response or autonomic response to those pictures, 75% of those individuals became violent criminals by age 18. Interestingly, 25% became pro-social and became things like police officers, bomb disposal experts, and so forth. Yeah, that is really interesting. And we have a whole podcast episode on Psychopathy. I think it was the second or third one of the series.

So if you are more interested in that, dive into that. let's go into the reactive type of or like impulsive. The impulsive violence or aggression is actually, of course, the most common and also in many ways the most complex form of violence. It occurs in a variety of mental illnesses, including the psychosis, mood disorders, personality disorders, anxiety disorders, PTSD. this is essentially an imbalance between impulse generation, which occurs in the ventral tegmental area of the brain, and a failure of the prefrontal cortex to evaluate the impulse, to weigh the consequences,

and when appropriate inhibit the behavior. all of us generate a variety of impulses, some good, some bad, including impulses driven by irritability or anger. If the prefrontal cortex is doing its job, it evaluates each impulse and basically says, no, don't do that, no, don't do that. Oh, really don't do that. And then occasionally says, well, that's okay, do that. In these individuals, essentially, there is a failure of the ventrometrial prefrontal cortex to function adequately. And consequently, the downward inhibition of impulses is impaired. And the person may act without thinking, this is the classic saying of leaping before you look.

Yeah, so in the predatory aggression you have, even a little bit increased of the medial prefrontal cortex, right? Yes. In the reactive aggression you have decreased activity. Yeah, and clinically these people are emotionally aroused. Usually something has happened to upset them, to distress them, and their response is to act out violently toward whatever has offended them. often without thinking about the consequences.

Interestingly, there is some research suggesting that when people exhibit this kind of behavior as an ongoing pattern, very large amounts of dopamine release in the ventral tegmentum winds up stimulating the dorsal part of the striatum up near the caudate, such that the violent behavior response becomes an almost an automated. response for some individuals. Yeah, I'm thinking of different types of issues that can lead to this. Would you consider like traumatic brain injury to be? Things like traumatic brain injury, some of the frontotemporal dementias, other dementias as they evolve, things like anoxic brain injury, some individuals intellectual disability may be associated

with this sort of very poor impulse control. Some of the personality disorders are also prone to very frequent poor impulse control, essentially all way coming down to the issue of not considering the consequences of a behavior before acting. I also think of drugs, both sometimes on drugs and coming off of drugs, can make people more like this. Oh, very much so. I was in the chemical dependency unit just this morning, and there was a patient coming off of heroin and methamphetamines and very strongly irritable, aggressive, and disruptive.

So there's that kind of dynamic of coming off of the substances as well. Yes. You know, both, well, substance use often impairs frontal lobe functioning, including the prefrontal cortex, such that people, again, don't exercise good judgment. And indeed, when people are coming off of a number of drugs, it may increase irritability, psychomotor agitation. Yeah, when I was rotating through the Padden State Hospital here, I remember one patient who was on methamphetamines and alcohol.

It seems like that combination led to her aggressive act, because now that she had been off of those, she was fairly regretful and, you know, sober-minded about what happened. Yes. Very aggressive act. Yes. Well, it's a particularly bad combination in the sense that alcohol or other sedative hypnotics, of course, impair prefrontal cortical functioning.

So the person's no longer able to exercise good judgment. And then on top of that, if they're taking a stimulant, the stimulants increase the amount of dopamine release, which generates a great deal in terms of impulsivity, drive to behave. And that's a very bad combination where you have an urge to behave and no ability to judge what you're about to do. Okay. And let's move to the third type. So this is psychotic aggression. Psychotically driven aggression is most often a result of delusional ideation or belief.

That is, the person holds a belief that they are in some way being persecuted, taking advantage of controlled and understandably believing that they become angry. and often that anger is expressed in terms of violence can also be associated with command auditory hallucinations to behave violently. Probably at this point I should say, although we're talking about mental illness and violence, and the mental ill do have an increased rate of violence

compared to the general population, The mentally ill are responsible for right around 5% of violent crimes, meaning, of course, that non-mentally ill people are responsible for 95%. So it's not as though we're saying that the mentally ill are responsible for a huge portion of the violence in our society. So when you say that, how do you parse out the three different types of aggression? would you consider more of the psychopathic aggression, the predatory aggression as not a mental illness? For the true psychopath, I think they probably are mentally ill,

but they're a very tiny part of the population. The estimated prevalence, now we'll never know accurately for sure, one to two percent of women probably score significantly on the psychopathy checklist revised, suggesting that they have substantial psychopathic characteristics. About 2 to 4% of men score have elevated scores on the PCR. Not all of those individuals, however, are violent. Many persons who are psychopathic are more interested in profit, if you will. they become the crime bosses, the people who pursue money, and they may not themselves be all that personally violent.

They ignore the rules of society and pursue personal gain, but are not themselves necessarily violent. It has been somewhat jokingly stated that the less intelligent psychopaths wind up in prison, and the more intelligent psychopaths wind up in government. There's an association between IQ and aggression. I don't know if you've seen that or how strong of an association that is. There is. We've done recently a study in the state hospitals looking at what correlated with persisting violence and across all of the types of violence,

behavior, cognitive deficits, particularly impairments in executive functioning, were associated with elevated rates of violence. And indeed, in one study done by Krakowski at all, they found that Haldol, olanzapine and produced similar reductions in psychotic scores on the pans. But the clozapine did a much better job of reducing episodes of violence. And what they found in association with that was that what the clozapine was adding was an improvement in executive functioning. Okay. Yeah, let's come back to that.

Let's continue with a little bit of the delusions that lead to violence. There was one study that you shared with me, Coyd-D-All 2013, which I'll share with the article that goes, along with this podcast. And he was looking at specifically first episodes of psychosis in about 458 patients and looking at what types of delusions led to violence and also what was associated with the delusions. And he found a lot of the time that anger was associated with certain types of delusions.

And that led to the violence. Anything else you want to bring out? out on that paper since you shared it with me. Yeah, that's an excellent paper for looking at the underpinnings of delusionally driven violence. And indeed, it points out that if people have delusional beliefs that are in some way persecutory in nature, they believe that someone is out to get them, that does a number of things. One, it removes the inhibitions against acting violently because of,

course from that person's viewpoint they are simply protecting themselves it also of course if people feel that they are being persecuted the you know an angry affective response to that is certainly understandable as well well you know my next door neighbor is persecuting me therefore I I'm angry about that I should do something to make the neighbor stop as your listeners may be aware just this last week. There was a young police officer in northern California who was shot and killed by a man who believed that the police were focusing ultrasonic sound waves on his house. I believed he was being persecuted by the police.

Yeah, so persecutory being spied on, conspiracy, those were the delusions that led to serious violence. And it makes sense, right? because if you felt that incredible fear and sort of like you need to protect yourself and if the delusion is congruent with that, right, then aggression and violence might be something to protect yourself. Yes. And, you know, in forensic psychiatry, it's long been understood that persecutory delusions are the most likely to produce a violent response. And in particular, persecutory

delusion associated with a command hallucination is a particularly potent route to violent behavior. You know, you believe you're being persecuted by your neighbor and the voice of God tells you that the neighbor is the devil. Well, that can lead to a very bad outcome. Now, in this study, they found that if you were a man, you had an odds ratio of 2.6. If you had antisocial personality disorder, you had an odds ratio of 6.5. If you used drugs, the odds ratio was 2.03 for major violent, to being in that sort of major violent group. So how does the interplay of those things relate to the delusions that lead to serious violence? Well, certainly if somebody is already experienced,

Persecretory delusions and for example they also are antisocial that is they tend to ignore Social rules well then prohibitions by society against being violent may not carry much weight with them if they are using substances many substances like alcohol are disinhibiting so any residual inhibitions they had about violently may evaporate in the face of intoxication or withdrawal. So basically these factors become amplifiers or multipliers of the underlying delusion and anger. And why do you think men are more violent than women?

Men are more violent than women in likelihood because we have historically all the way back to hunter-gatherer societies, the men were typically the hunters, which involves violence, while women were gatherers more often than not. And consequently, I think men have a long-standing evolutionary tendency toward more frequent use of violence, which isn't to say women can't be violent, but if you look at the relative rates of violence between men and women, men are clearly more violent. Some people have also cited testosterone poisoning as a factor.

You know, I looked at an interesting study that it was a little bit more nuanced than just giving testosterone. They were looking at what types of aggression increased, and they specifically found that the type of aggression that increased with testosterone use was not general aggression, but it was if someone does something against you, you're more likely to stand up for yourself. Yes.

Testosterone in many animals, including humans, in part determined social hierarchy. I think we're talking about aggression and violence, mostly in the negative sense, but from the standpoint of survival, obtaining resources and so forth, violence and aggression does have a positive side as well. You know, what also occurs to me is how much we sublimate our desire to be aggressive

for violence now. In, you know, the movies we watch, in the TV shows we watch, I think it's something like by the time you're 18, you've seen 10,000 violent acts. Video games are incredibly violent, some of them. And often I think about how unique we are in this day and age that we could sublimate these sort of aggressive drives so much and so much more than any other time in society. We sublimate a great deal of violence. And in fact, you could say that the healthiest outcome for our aggressive and violence

impulses, aside from when we are in reality needing to defend ourselves or defend our society, is when we use our innate ability to be aggressive to engage in things like healthy competition, sports, for example, or to provide motivation and drive to achieve, those things are derived in many ways from the same structures, but with control and modulation about what's appropriate. Yeah. Often when I hear someone talk passionately about something they're doing, they flash micro expressions of anger.

And at first I was curious, like, why are they doing that? Are they angry about something? And then the more I listened and watched, hundreds of people talking about these things that they're passionate about, things that they're launching into, often, I think the anger is part of the energy to help them overcome obstacles.

And so it's a good thing. It can be a constructive thing. Now, obviously, anger can be a very destructive thing at the same time. And so it's kind of like, how do we seek to find our natural energy in this and use it in productive ways to move society, to move our families forward? I think that's a great challenge we have and something that we won't be able to solve in this episode. Well, no, I don't think we'll be able to make the entire world pro-social in an hour.

But I think that is the difference we're getting back to us in many ways of the same division. We have the same underlying biology, but the underlying biology can be poorly controlled and can lead to violence and criminal behavior, or it can be controlled and driven toward pro-social goals. Yeah. And it's sometimes hard. I'm working with a couple of people who are incredibly driven and have lots of motivation and naturally probably are more aggressive.

And it's like, how do you help them? funnel all of that energy and it's something that will will help society and not hurt society, you know? And sometimes that can be difficult. Yeah, and also help them and not hurt them, I think, for all individuals, whether we're talking essentially about any of our innate drives, there's always an element of needing to balance those drives and to not become a so singularly focused that we lose a sense of being able to modulate our thinking, our behavior, our emotions. Yeah, I think of aggression as like, you know, imagine most of humanity was tribes.

And so, you know, aggression allows someone to climb up in the dominance hierarchy within a tribe and protect themselves from other tribes. and aggression helps them, you know, eat and survive. So there was many ways that aggression has played out for many, many years. And I would say even dating back to like, if you look at animal psychology, there's a lot we can learn about aggression and dominance hierarchies and, you know, how apes sort of interact with each other, of form alliances, you know, treat people in their clan nicely,

give them massage, give them, you know, a lot of, like the, the least, leader of an ape sort of clan will often spend a lot of time grooming other men. Yes. As a way of creating alliances, as a way of, you know, basically establishing friendships and relationships. And a lot of it isn't violent, but the violence comes out when the clans come against each other, you know, when there's one ape wandering away from his clan and two apes from another clan are there, you know, they may attack the,

that one single ape viciously. And in other circumstances, if an ape is taken away from his clan, who was a dominant ape for a couple days and then brought back into the clan, now a couple of the men may have formed a new alliance and may rise up against this prior dominant ape. And so if there's been, you know, when they take apes and they try to separate them, they'll cling to each other, not wanting to be separated from each other for, I think, the fear of these sort of alliances forming if they're left alone for a couple days. And so one of the most dangerous periods in a zookeeper is if one of the dominant apes gets sick and they have to take

them away for a surgery or something and then bring them back into that clan, it can be a very, it can be a very dangerous time. Yeah. And indeed, as human beings, we are, also primates. We're one of the great apes and many of our social interactions and group structures. You can watch the same sorts of shifts in alliance and effects of absence and aggression play out as well as the social interactions. I was struck in visiting the San Diego zoo that outside their ape exhibit they have a plaque describing the social interactions of the the apes and frankly you could put the plaque outside the local bar and it would be essentially as accurate that's really funny um yeah it's it's interesting to kind of observe animal behavior and

human behavior and then look at the similarities and differences and i think we do have more of a frontal lobe, we do have more executive planning, and we do have higher verbal centers as well. And I would say that good, um, good philosophy or good spirituality allows the individual maybe to be less violent and to sort of transcend those sort of base instincts of, you know, what's in our, what's in our DNA from, from, uh, you know, millions of years, right? Yes. Um, to transcend it, I think, in the sense that, as we were talking about, to think about our drives and to decide to do something positive with them and to maintain a balance that without philosophy and without language would be much more difficult

to do. Right. Which is why I think, you know, to some degree that the lower IQ people have a higher degree of violence, now some of the most difficult patients I have that I want to kind of get your thoughts on are, you know, patients who are autistic and very violent and what, what you think might be the best treatment and where they would fall in in the three categories? Certainly, and for those who have intellectual challenges, they most often exhibit impulsive violence. Of course, that's not different than saying that impulsive violence was the most common category found, regardless of diagnosis. But particularly in autistic spectrum disorders,

the person may have a great deal of difficulty processing or understanding their own emotions. If there are significant intellectual deficits, then elements of being able to judge a response or to moderate a response as opposed to simply responding to the environment. becomes a much more difficult challenge. You know, the underlying pathophysiology of the autistic spectrum disorder

suggests that, in essence, the connections between neurons and the autistic brain are not what they should be, and they're not differentiated and essentially put together quite right, such that information processing and emotional processing are often fragmented or idiosyncratic, as well as the person's sensitivity to the environment and ability to interpret the environment may be impaired as well. So I want to jump into treatment, and maybe we can go through the three types and talk about the treatment of aggression and how it might differ within the three types. So starting with the more predatory aggression, the psychopath, what is treatment options, or what are your thoughts on that?

So far, in terms of the severely predatory, violent individual, most of society's solutions have been forensic or custodial in nature that is to simply control the person's behavior. behavior by putting them in prison or confining them. There are some interesting research lines suggesting that enhancing intellectual empathy, which psychopaths are capable of, may make them less violent. There are also some interesting experiments going on with things like oxytocin, a hormone that tends to increase affiliation and collaboration that may have a moderating effect on some psychopathic behaviors. Certainly in

terms of pharmacology though we don't have any highly effective treatments for psychopathic violence or aggression. The most clearly defined treatment category is the psychotic violence and that's largely because we do have effective antipsychotics, beginning with the dopamine antagonists and for those who are more treatment resistant. We have chlozapine, which is clearly both effective in treating psychosis, and also frankly in reducing violent behavior, criminality, and suicide independently of its antipsychotic benefits. Impulsive aggression and violence is a more pleomorphic field more heterogeneous.

There have been a number of agents that have shown efficacy. For example, things like the SSRIs and trazodone and dementing illnesses in the elderly. Mood stabilizers and people with things like borderline personality disorder to agonists in people with things like like autism or traumatic brain injury. Say more about the alpha-2 agonists. Alpha-2 agonists basically interact with the locus serulius and the brain stem and fool it into thinking that enough norapinephrine has been released.

So that nucleus, which is the source of most of the brain's norapinephrine, quiets down, doesn't secrete as much in oraphenephrine, the effect of that and the temporal lobe and the ventral tegmentum in particular is to make those areas more quiet. So the person is less impulse driven. There's less drive to do things. So specifically in the more impulsive aggression, you think that what would you say would be the normal starting doses of like an alpha two? Typical, one of the most commonly used drugs has been clonidine. Doses have to be started low, usually 0.1 milligram initially and then gradually titrating up to as much as 0.3 milligrams BID. The risk with that and with guanphasine are, of course, if you get too aggressive with your dose titration,

And these drugs also cause sedation and lower blood pressure. So you may make the person sedated and orthostatic if you increase the dose too rapidly. Do you ever use patches or would that be? Yeah, patches are very useful for people who will cooperate with them. Okay. And keep them on because it provides you a nice, steady delivery system. depending on the context and the particular patient, they may be more or less cooperative with a patch as opposed to a pill.

Okay, so with the more impulsive aggression, mood stabilizers, treating the underlying affective disorder? Yeah. For example, in, well, certainly, for example, in bipolar illness, people who are hypomanic or manic become impulsive, people with borderline personality structure are prone to be impulsive. And in many cases, if you can decrease the person's affective tone, if you will, make them less emotional, they'll be less driven by their emotions and have essentially a bit more of an ability to think about what they're about to do.

So what would be the categories of meds that would decrease the affective tone? And are we talking about decreasing the like limbic tone here? Yes. We're talking about lithium, which depletes triphosphonocetol, second messenger in the limbic system. We're also talking about drugs like valproic acid or divalproex that inhibits voltage-dependent sodium channels and also produces some changes in second messenger populations. historically people have also used other mood stabilizing drugs like carbamazapine, less popular because of all of its potential adverse effects.

What about antipsychotics for the impulsive group? The antipsychotics, if it is purely an impulsive group like, for example, traumatic brain injury, the antipsychotics have shown no benefit. In fact, what they tend to do is worse than cognitive performance. What about like autism? Certainly the antipsychotics have been used in autistic spectrum disorder and there is some evidence to suggest controlled evidence to suggest that for example, risperidone can be beneficial. Okay.

The other other medications like the Alpha II agonists and the mood stabilizers also may have a role in some individuals. There's no magic bullet. if you will for autistic spectrum disorders. More often people are in the position of identifying a particular target symptom, like excessive emotional arousal, and then attempting to target that symptom with a medication that they've chosen. Okay. Well, I like the Alpha 2 thing was a new idea for me.

Are there any specific studies? that come to your mind regarding that for the impulsive group? Or would you also do that for the psychotic group? In fact, one of the articles that I think I sent you to go along with this podcast is called Psychoformicology of Persisting, Persisting, Aggression and Violence. And indeed, a component of that paper is a review of the treatment of impulsive aggression and violence in a variety of context. traumatic brain injury and the dementing illnesses most providently.

That's really great. Okay. I'm going to tell you how that goes. I have a couple of those cases that are just really tough. Okay, so like let's say you had a patient who came to you who was already on like an antipsychotic, an antidepressant, you know, let's say Risperdal, 2, TID and antidepressant like Prozac, 20,000. and still aggressive, what would be sort of some of your thoughts on what you would do next? For the autistic spectrum disorder, I might take a look at the antidepressant.

The SSRIs in particular can idiosyncratically increase irritability in autistic spectrum disorder. So I'd want to know historically when the SSRI was started, did it reduce or increase irritability? the alpha-2 agonists may be useful in this context mood stabilizers may be useful if the violent or aggressive acting out appears to be in particular in a younger well adolescent male and it carries overtones of sexual aggression, then consideration of use of essentially an anti-androgen treatment may be worth considering. Interesting. Because the aggression can sometimes be tied with sexuality or the sexual

impulse is leading to the aggression? Well, in terms of considering sexuality and aggression, both are in the brain relatively close together. Both are modulated by the amygdala. And indeed, particularly in younger males who have relatively high levels of testosterone, people with intellectual disabilities or with autism may, as they go through puberty and interadolescence, they may become sexually aggressive. sometimes not easily identified as sexual aggression,

but exhibiting a pattern of aggression specifically toward members of the opposite sex most often. And in those cases, giving them a GNRH stimulant like luprolide and decreasing their testosterone may help alleviate the aggressive behavior. How would you differentiate that the aggression is, like let's say the aggression is happening towards women, how would you differentiate if this was from that sexual sort of frustration versus a just easier target?

Because specifically with some patients, you know, as the autistic patient gets older, they're very strong, much stronger than mother, but not as strong as father. and so they can kind of get away with it with mother but not with father. It can be very difficult. Sometimes it comes down to doing essentially an ABA trial where you introduce the person to a shorter acting form of luprolide to decrease their testosterone level

and observe what happens to the aggression and then take them off and assess whether the aggression goes back up and try to make essentially make a judgment based on that kind of clinical data outcome as to whether the luprolide is a useful approach in this particular individual.

If it is useful, then the nice thing with luprolide, for example, is it comes in a number of formulations up to an including a six-month depot formulation so that dosing becomes easy and you don't have to do something every day that way. When people are engaging in anti-androgen treatment the goal after measuring a baseline

testosterone is to reduce the circulating testosterone by about 75%. You don't want to reduce it completely because that puts the person at increased risk of osteoporosis in the long run. So you also mentioned in the CNS Spectrum's paper that you co-authored on the California State Hospital Violence Assessment and Treatment Guidelines. You talk about getting blood levels of various antipsychotics and the ideal ranges. Yes. Yeah, and that's a point I want to underscore for everyone who is a prescriber out there.

Dose is a very, very, very, very poor guide. as to the adequacy of treatment. People vary tremendously in terms of, one, adherence to medications, two, absorption and metabolism of medications. In fact, in people who are faithfully taking oral medications, the plasma concentration may vary as much as 40-fold across the entire population. So saying, well, I gave him an adequate dose isn't really

saying much measure the plasma concentration to find out if your treatment is truly adequate. There have been a number of studies done over time suggesting that one of the main reasons for treatment failure in psychiatry is inadequate treatment. And I'll give that in my resource library on my website the different levels and the recommended levels, and I'll put a link to that in the show notes. and I refer to that quite often and I've started getting blood levels and been surprised that they're often very low

even when you're giving big doses of the medication and you get the blood level back and you're like, well, this is the very bottom level of the normal range. And often incorrectly people conclude, well, the patient's not a responder to this medication. Well, no, you don't know if they're a responder or not because they've never actually had a trial

of the medication. One of the issues I've come up with since working or learning this from you was as I pushed the level of the medication up, like there's significant side effects. One patient on Clauserill as I pushed him up and he was still at a lower range of therapeutic benefit. His sedation was so severe during the day that he was having a hard time drive. having to work, going to work. Any thoughts on how to treat some of the side effects as you are pushing up the dose? Yeah. Well, certainly, depending on the side effect, there are different things you can do to mitigate them in terms of sedation.

Probably one of the chief things you can do with chlozapine is the reason for dividing chlozapine initially is because of its alpha adrenergic antagonism, producing orthostasis, and, and its antihistamine effects. It's a great antihistamine making people sedated. You more or less have to divide the dosing initially to be sure the person has a blood pressure. But after their alpha receptors accommodate and you reach what is essentially their treatment dose, you can often consolidate Clozapine to bedtime only, which gives them a lower daytime plasma concentration.

concentration which may allow them to wake up people have used also drugs like modafinil to attempt to make clozepine-traded patients more alert it has failed in controlled studies to be effective but you may idiosyncratically find individual patients who respond to 100 or 200 milligrams of modafinil on the morning and then more alert and awake. Even though the systematic data is negative, it may be worth considering to make the person more alert. You'll know within a few days it either works or it doesn't. We've even had a few patients here who both to control impulsivity and to make them more alert. We've put

them on low-dose controlled release methylfinidate, which interestingly, if the person's psychosis is well-controlled, meaning you've tamed their D-2 receptors in their limbic system, you can target their D-1 dopamine receptors and their prefrontal cortex and may actually get an improvement and impulsive violence by doing that. That's very much a nuanced treatment. because you're wanting to stimulate one set of dopamine receptors while inhibiting another. Yeah, I've done that successfully one time with one patient, and he's done well in college and progressing well, despite having very significant schizophrenia. Yeah.

Well, I think people sometimes forget that the positive psychotic symptoms are by and large the product of dopamine D2 receptors in the mesolimbic pathway. The negative symptoms and the cognitive deficits are often a lack of dopamine stimulation in the prefrontal cortex, which is D1 receptors and a few D3 receptors. Most of our antipsychotics have little or no affinity for the D1 receptor. So it's an open target if you can manage that balance between stimulating the D1s and not stimulating the D1s. the D2 receptors. Because I work in a forensic setting, we always do use formulations of stimulants that are resistant to diversion and abuse.

In a concerta, for example, comes in a hard capsule that's short of having a laser drill, you'll have a hard time getting the medication out of the capsule. Less dexamphetamine, for example, also is a possibility because in its native form, it's a pro-drug if you inhale it or inject it, nothing happens. You have to dissociate it from the lysine amino acid before it becomes a stimulant. What would you say about, I've had a couple ADHD patients who say that they get a little bit more angry at the end of the day as the medication is wearing off. Any thoughts on what you would do to help that person? You may want to move their dosing as late as they can tolerate in terms of inducing.

insomnia. One of the problems with all of the stimulants is as the stimulant plasma concentration declines, essentially the person's ADHD symptoms then tend to reemerge because they're losing the stimulatory effect on the prefrontal cortex. One of the other side effects I wanted to pick your brain about is one patient I was increasing their risperdol and they developed aceshesia as we were trying to get into therapeutic dose ranges. We've talked in the past about this, you know, propanol 20, TID and metazepine 15 at night didn't seem to quite calm it down enough. Any thoughts on if you would try other medications or if you would move to another antipsychotic? I might move to another antipsychotic.

choosing one that perhaps is a less robust D2 antagonist. The other thing about dosing with the antipsychotics is people very commonly get taught to divide antipsychotic dosing. Almost all of the antipsychotics can be given after titration at bedtime only, and that will substantially reduce the prevalence rate for acethesia and as well as for the other movement disorders and neurologic signs and symptoms associated with d2 blockade, because the basal ganglia is in essence a part of our reticular activating system.

When we go to sleep, we don't have movement disorders. And if the peak plasma concentration of the antipsychotic occurs while we're asleep and then is at a lower level during the daytime, we may be, able to escape many of those signs and symptoms. Okay. That's helpful. Do you have thoughts on how high you would dose the propanol or the remerone to reduce the aceshesia as well?

The remoron has only been studied at 15 milligrams so that nobody actually knows if the effect gets better or worse at higher doses. Rimmeron at low doses primarily is a 5H2A antagonist and 5H2C antagonist which is why it makes people hungry as well as being antihistamineic as you increase the dose it begins to increase the amount of noraphenephyne that is secreted and some you would expect in many people if the noropinephrine is going up it might actually make the acethesia worse so I would not say that you can't try it at a higher dose for acethesia but don't be surprised if you get a response opposite what

you were hoping for with the prokronolol you can titrate it up if you titrate gradually to fairly high plasma concentrations and at least In studies, it does continue to show a dose effect curve up to around 80 to 120 milligrams a day. If you're using higher doses, you may specifically want to use the long-acting formulation to make the dosing easier. Okay, that's helpful. I know we've focused a lot on pharmacology and the brain and categories. I think it might be worth it to talk a little bit about psychotherapy, because it is a big treatment for aggression that has long-term efficacy and certain types of aggression. Anything in particular that comes to your mind that you want to emphasize there?

Yeah, certainly in terms of psychotherapy, there have been a number of anger management approaches that have been used over time. and indeed for many people the violent behavior or aggressive behavior reflects a lack of alternative behaviors to choose from and certainly helping the person evaluate other things they might do in response to their angry feelings or in many cases even being aware of their anger may be helpful to them in learning to manage their angry impulses and again, push their anger or aggression toward a more pro-social response. Yeah, and I think, you know, different categorizations of reasons for why someone might be aggressive have different treatments in psychotherapy. For example, borderline personality disorder, you know, dialectical behavioral therapy or mentalization-based

therapy or transference-focused therapy would be helpful in reducing aggression. you know if someone's manic and aggressive then yeah maybe just more of building a relationship with a patient where the patient believes that the medications that you're prescribing are going to be most helpful and that might be what is most helpful in treating those patients in schizophrenia you know once again building that therapeutic alliance building that connection where they trust you enough to take the medication and sometimes, you know, it's going to be hard to get to that point, but I think that compliance and therapeutic alliance within schizophrenia is absolutely necessary. One thing I would say about that, and this is a fault of American psychiatry, is for many

of our schizophrenic patients, we should really be using long-acting, injectable formulations of the antipsychotics much earlier in treatment. Interesting study that was done looking at at antipsychotics comparing each oral formulation to its own depot, found that the depots were invariably more effective and actually over time reduced mortality compared to the oral by about 30%. Right, because, you know, in the KD trial, what is it, 70% of people with schizophrenia had poor compliance or noncompliance? Yes.

Yes. Yeah. One of the false in psychiatry, of course, is that, you know, is that. everyone goes, well, yeah, I've read the adherence data, but my patients would never do that. Well, yeah, they will. Yeah, so absolutely, I think that's very important, Dr. Cummings. We have to imagine that our patients will sometimes hide the truth from us because they want to please us. And we have to assume that it's going to take a while to build that relationship to get them to trust us enough to talk to us.

and we need them to feel psychologically safe enough to tell us when they disagree with us or when they're not taking it. And that really comes into, I think, one of the most important parts of the psychotherapy would be that therapeutic alliance and that ability to build that connection that would increase compliance so that they can move out of this aggressive state or move out of the psychosis. Mm-hmm. And in particular, if you can all lie with the patient and begin to use some elements of motivational interviewing where you and the patient can agree that you have a common goal, you can use that goal to encourage them to use the treatment or to view the treatment as a means of achieving their goal. Yeah. Yeah, that's really important. So any final thoughts, Dr. Cummings, things that you would want people to for sure take away from this episode. I think that one of the things that has become apparent because of the system I work in is that violence and aggression itself is a clinical construct is deserving of much more attention than we've given it in the past as a specialty. you know, not only is violence and aggression difficult for our patients because of the potential consequences for them, but of course is also a major burden for most often family members or close associates. So the more we can do to help our patients become more pro-social

and to divert their aggressive impulses into positive avenues, the better. And on that point, I'm going to put out a unique ending is that if this has been helpful, but you have questions, if you send me any of your questions, we will have a follow-up episode with Dr. Cummings, in which we'll literally read your question to Dr. Cummings and then we'll discuss it. If you email me or send me a message through social media, my email is DR at psychiatrypodcast.com. and we will bring that into the next episode. I think it would be good to do a follow episode up on this and go through specific cases, go through details about this because this topic is so important. And I would say it's probably one of the least,

it's the least trained topic that I was trained on during residency. So I think it's important for providers to continue to better understand how to treat aggression, and how to treat anger, how to decrease violence. And so, yeah, if you have any questions, shoot me an email, shoot me a text through my social media. The links will be in the show notes. And if you want to get to see me from this, you can follow the link to the website as well. All right.

Thank you, Dr. Cummings. Thank you.