Aggression Management – Pharmacological Interventions

View episode transcript

Featured guest: Nasuh Malas, M.D., Department of Psychiatry

Objectives

• Identify medications to utilize when a patient is agitated

• Reflect on situations when medication is indicated to address agitation

Resources

• Best practices for evaluation and treatment of agitated children and adolescents (BETA) in the emergency department: Consensus statement of the American Association for Emergency Psychiatry

CME

Credits available: 0.75

Visit our CME course overview page for CME credit, or complete this survey for social work CEUs.

Transcript

Dr. Christina Cwynar:

Hello and welcome to our podcast Breaking Down Mental Health with myself, nurse Practitioner, Dr. Christina Cwynar, social worker Syma Khan, and Child and Adolescent psychiatrist Dr. Heidi Burns. We are joined again this week by Dr. Nasuh Malas to continue our discussion about aggression in the pediatric population, with a focus this time on pharmacological interventions.

For those of you that missed Dr. Malas's introduction, Dr. Malas is a service chief for Child and Adolescent Psychiatry at the University of Michigan. He also serves as the medical director for the pediatric consultation and liaison psychiatry service at C.S. Mott Children's Hospital. He has leadership positions in the emergency and consultation, psychiatry with the American Academy of Child and Adolescent Psychiatry in American Association for Emergency Psychiatry, and was involved in the developing of the pediatric beta guidelines for the management of agitation and aggression.

None of the speakers here today have any conflicts of interest or financial disclosures. We will be discussing medications today, which will include off-label uses of medications. This podcast does not sponsor and is not sponsored by any pharmaceutical company or product. The medications discussed today are based on the speaker's clinical experiences.

Thank you, Dr. Malas for joining us today.

Dr. Nasuh Malas:

Thank you for having me. I'm glad to be talking about this topic.

Syma Khan:

Last week, we talked a lot about what can cause aggression, evaluation and non-pharmacological interventions for agitation and aggression. This week, we're going to focus more on the pharmacological interventions available for the management of agitation. Dr. Malas, when should medical providers and families start considering medications for the management of agitation?

Dr. Nasuh Malas:

There's a few factors to consider when we're thinking about medications as part of the treatment plan. For somebody who's at risk for aggression or exhibiting aggression. First of all, it's really important to understand the family's values and perspectives on medication use to address any potential misunderstandings or knowledge gaps that the family may have and make sure that the family is invested and on board with medications before considering that. You also want to be thinking about the nature of the child's underlying physical, emotional, developmental, cognitive needs because there are certain conditions that are more conducive to medication use and other conditions that may not respond as well, so being aware of that is helpful.

The severity of the presentation can be also another indicator. The more severe the behaviors are, the more impairing they are and the more frequent they are. It may require a combination of nonpharmacologic and pharmacologic intervention, as well as the specific issue in the moment. We know that there is underlying risk before the aggression occurs, but that aggression is highly heterogeneous and diverse in its presentation. We covered that a lot in the last talk. But just being aware that in a given moment things can change and may warrant medication use, whether it's as needed for that time or potentially adding that because of the given presentation of the child.

Dr. Heidi Burns:

Let's take a few minutes and talk about the common medications that we might use in agitation management of pediatric populations. Dr. Malas, you were involved in developing the pediatric beta guidelines on the management of agitation and aggression, and we talked a lot last week about the ideas about what precipitates agitation, really being an investigator and sort of looking to see what contributed and caused the current state that the patient is in, trying to think about what state that they're in, sort triaging them and doing non-pharmacologic interventions. But what do the guidelines say about the next steps, once you've sort of gone through the possible non-pharmacologic options that you have and you maybe are still dealing with a youth that is in a state of aggression that's quite unsafe. What would you do then?

Dr. Nasuh Malas:

That's a great question and I think something that we often grapple with when we are managing aggression is when to who progress to using a medication or coupling medication with other interventions. Two things I just want to address off the bat. It's really important to constantly be thinking about what's going on diagnostically. We can't create solutions to a situation until we really understand what the problems are that we're addressing. A child or adolescent presenting with refractory aggression or progression in their behavior may actually be due to a faulty understanding or a limited understanding of what's going on with their presentation. That's first and foremost, constantly thinking about that throughout the process.

Additionally, we want to make sure that non-pharmacologic intervention is continued to be used throughout the process, because even with medications, the actual gold standard approach of treating aggression and frankly any behavior is to continue to provide that non-pharmacologic intervention, both preventative and active intervention, as well as considering the utility of the medication. But once you've decided that you need to pursue a medication, again, the framework that we've used and we talked about in the last series was really talking about thinking about what is driving that agitation or aggression and then selecting the medication based on the underlying etiologies or etiologies that you believe at a given time is driving that agitation or aggression.

That may evolve over time, so you may initially see a child that you identify as being delirious from a medical condition, the delirium resolves, and then they become anxious and traumatized. Your management should evolve with that evolving understanding of the child. When we think about medications, there are a few classes that we typically consider broadly for the management of agitation and aggression. I'll name a few and hopefully we can take a deeper dive on some of these.

One class that a lot of folks are familiar with are benzodiazepines. They act on a neurotransmitter class called GABA in the body. But benzodiazepines would be medications like lorazepam or diazepam, and there are a lot of indications for their use. There are some reasons not to use them. We can certainly talk about that. Another class of medications that's commonly used are neuroleptics. We also commonly call them antipsychotics. I prefer to use the word neuroleptic because most often those agents are actually used for non-psychotic indications. So for youth that have mood or anxiety issues, developmental issues, delirium, there's a whole series of different reasons why you might use a neuroleptic or an antipsychotic. Those would be medications like ziprasidone, risperidone, aripiprazole, haloperidol, olanzapine. There's a whole series of them and there are broad indications and there may be some reasons not to use them.

Other medication classes that we use include Alpha-2 agonists, medications like clonidine and guanfacine. Sometimes we use antihistamines like diphenhydramine or Benadryl, as well as hydroxyzine. In some cases where patients are distressed, there are some studies that show that stimulant medications and youth with ADHD can be helpful acutely in managing aggression risk. There are other classes of agents that are less commonly used, different mood stabilizers and other agents that may be specific to a given population.

But those just kind of give you a sense of the spectrum of different medications, and what I typically think is trying to have a simplistic model of what do you go to first knowing the patient's needs, knowing the family's information that they've given you about past experiences, what the situation warrants, but really kind of thinking about a few agents that you have in your toolkit that you can go to initially. And then as you learn more about the patient and as you observe that response, reflect on that, and think about the overall clinical picture, then you can adapt your management strategy so it's a little bit more customized over time.

Dr. Christina Cwynar:

Dr. Malas, you introduced a few broad classes of medications to us, but why don't we start taking a little bit of a deeper dive into those classes and talk about why you would decide one class over another and kind of some of the benefits and risks with each class. The first class of medications that you mentioned was the benzodiazepines. We use these commonly for highly-agitated patients, but what is the best situation to use a benzodiazepine, how do they work, and what side effects should a provider be watching out for?

Dr. Nasuh Malas:

It's a broad class and each medication has unique characteristics that we should consider. Things that I think about is route of delivery of the medication. So can the person take an oral medication? Do they need an injection? Do they need to the medication to be delivered through the IV? Is there a transdermal or a skin patch that can be used in certain patients that may benefit from that type of approach? You want to be thinking about how that medication's delivered.

You want to know what the time of onset and time to peak effect is. That includes an understanding of the half-life of the medication. Typically after five half-lifes, the medication has been completely eliminated from your body, and so being aware of that can help you anticipate how quickly a medication will act and how long it may stay in somebody's system. Being mindful of that can be really helpful in pairing how you intend the medication to work to what the situation is. You also want to be aware of the people around you and their understanding of the use of a medication. Using a medication that's unfamiliar to a setting may actually because some distress because people are just not aware of how to deliver it or what to look for. Then obviously thinking about what you're trying to manage can be really helpful.

In the case of benzodiazepines, common indications that we'll use benzodiazepines for are oftentimes any type of substance-induced agitation. We have certain ways we can use benzodiazepines. One example would be alcohol withdrawal. There are protocols where when somebody's withdrawing from alcohol, which can be very dangerous, it can be sometimes life threatening in certain people, using benzodiazepines to be able to facilitate a smoother discontinuation of the use of alcohol and the managing the withdrawal symptoms can be helpful. There are psychiatric conditions, so severe anxiety when it's really impairing, distressing, and involves aggression may sometimes warrant using benzodiazepines.

Frankly, there are times where benzodiazepines may be used either in conjunction with other medications like neuroleptics or as a standalone when the severity of the presentation is quite high. One thing we need to be mindful of with this medication class is that some youth, younger youth, youth with developmental disabilities or youth with cognitive limitations, or just frankly folks that have never been exposed to this medication class can have a paradoxical reaction where they can actually become more agitated and aggressive with the use of this medication. We have to be mindful of that.

Then there are other specific populations that we would not want to use this medication class for. The one that most comes to mind is youth with delirium. There is actually good data to show that using benzodiazepines in youth that are delirious in the setting of critical illness or systemic disease, physical disease can actually get worse on benzodiazepines.

Dr. Heidi Burns:

I think that's really helpful and brings to mind something that I try to think about a lot is that youth are not just tiny adults. They operate differently. They metabolize things differently. We can't sort of use the same strategies all the time that we might use with an adult population. But that's very helpful to kind of think about the ways that we can use benzodiazepines in certain specific populations that really would benefit and some that actually would be quite harmed from that type of medication.

What about the neuroleptic or otherwise known as antipsychotic types of medications? What populations would we use that medication in or what situations would we use that medication in?

Dr. Nasuh Malas:

The antipsychotics are what I referenced before as neuroleptics. Those medications have wide uses as well. We have to be mindful of the use of these medications and be good stewards because there is a risk over time of developing significant metabolic symptoms, things like weight gain, diabetes, increased dyslipidemia. There's a variety of factors that we need to be cognizant of with the chronic use of these medications. In addition, these medications also can cause what we call extrapyramidal symptoms with use where you can develop involuntary movements, stiffening of muscles, and even restlessness called akathisia that can look like agitation but is actually a side effect in the medication. I provide that caution because although there's great utility with these medications, there is also significant risk that we need to be mindful of.

We commonly use these medications for a variety of different indications, one being delirium, which I talked about earlier. We don't want to use benzodiazepines. We do want to use this class of agent if the aggression is not responding to other nonpharmacologic interventions and adjustment to sedation practices.

Another group that sometimes may require neuroleptics are our youth with intellectual disability, developmental needs, or sometimes our youth with autism. We really need to think critically about whether or not that's indicated. Some of our youth with mood disorders, whether it's a depressive disorder, bipolar disorder, or maybe a mood disorder, whether it's some psychotic features, may benefit from this class of agent when they are distressed or aggressive. That includes kind of a loosely-defined construct that is getting a lot of attention from researchers is this concept of emotional dysregulation, where folks just can't manage emotions. If they develop strong emotions or get distressed, they basically lose control of the ability to kind of manage that and then it manifests with aggressive behaviors. In those individuals, sometimes we may use neuroleptics or antipsychotics for management.

Then just like benzodiazepines, sometimes the severity of the presentation, as long as there's no contraindication for use, may also warrant the use of antipsychotics.

Syma Khan:

Speaking about neuroleptics or antipsychotics, in many emergency rooms, it's common practice to utilize haloperidol or Haldol. Why do you prefer olanzapine over haloperidol for pediatric patients? When should we consider use of haloperidol and how does haloperidol work and what side effects should we be concerned about?

Dr. Nasuh Malas:

Haloperidol is a medication that we've had in psychiatry for some time. It actually has been tremendously beneficial since its development because it's provided an opportunity for a lot of individuals who did not have an avenue for therapeutic support to receive a medication that could help with a variety of symptoms including psychosis, mood disorders, other behavioral disorders in the context of developmental factors or just difficulties controlling impulse impulses or managing executive functioning. However, it carries some significant risks.

One of those risks is extra extrapyramidal symptoms. With ongoing use or sometimes even with short term use at higher doses, you can see some pretty significant extrapyramidal symptoms, those involuntary movements that can sometimes be very distressing for patients and families, as well as if we don't address them, can be more intractable and difficult to manage over time. In addition, haloperidol does carry some risk from a cardiac perspective, in that for some youth it can prolong the resting phase of the heartbeat or what we call the QT interval. If that occurs in some youth, it may put them at higher risk for arrhythmia and other cardiac complications. So we have to be mindful of that. It can also lower blood pressure. And it can cause some weight gain over time, but typically we're thinking about these other side effects.

The value of haloperidol is it does come in an IV form and it does work fairly quickly. It does have a longer half-life, so when people do receive this medication, they may have the effects of it a little bit longer in their system. Ultimately it can be sedating, especially if you've never received it. Although it is helpful in certain populations, it can work quickly. There's different ways to deliver it. We've shifted more to what we call the second-generation antipsychotics or neuroleptics like olanzapine, or clotiapine, risperidone because they have less of those risks. The risks are more related to those metabolic symptoms that I mentioned before, but they're generally better tolerated.

Especially with olanzapine there's been some head-to-head studies between olanzapine and haloperidol in the management of agitation and aggression, predominantly studies in the adult literature, but some in the pediatric literature as well, that have actually shown them to be equally efficacious at managing aggression, but that olanzapine is much better tolerated. There's actually another study, a very well-known study in psychiatry called the Katie Study that actually showed the use of olanzapine was one of the more well-tolerated medications in the class of neuroleptics and that patients were more willing to use it over time despite the risk of weight gain.

When we're thinking about haloperidol versus one of these second-generation antipsychotics, we're thinking about what's the route of delivery knowing that haloperidol can be given through IV when these other agents can't, how quickly do we need it to act and knowing we can give it through IV, haloperidol may be required if you need immediate effect, although you can use some of the second-generation antipsychotics that have quicker effect, especially if you give it as an injectable, and then what types of side effects. Generally most pediatric practices are going to the second-generation antipsychotics and only rarely using haloperidol if there are specific situations that warrant its use.

Dr. Christina Cwynar:

Thank you for all that information on neuroleptics and the differences between our first generation and second generation.

Let's jump to maybe another class of medications that you mentioned, and that's the Alpha-2s, and maybe we can clump in the antihistamine since I think they go a little hand in hand there.

Dr. Nasuh Malas:

In my practice, I do use Alpha-2s a little bit more. You will see throughout the country there is some variation. We do have the guidelines that were mentioned before, but there's still not wide consensus on the fact that certain medications should be used or not. Typically we're taking the evidence, taking these guidelines, and then applying our judgment to the specific situation and all those factors I described before and making a decision. That's where Alpha-2s and antihistamines can be helpful, just increasing our toolkit of options that we can utilize to support a child when they're agitated or aggressive.

The Alpha-2's, primarily we're using shorter acting agents like clonidine or guanfacine. There are longer-acting forms, but we typically don't use that for the acute management of agitation or aggression. It's important to be mindful that these medications can affect heart rate and blood pressure, so if somebody has a risk in that regard or has a cardiac history, you want to make sure it's reviewed with their primary care doctor that they don't have any risk that maybe entailed with the use of these medications. But otherwise, the only other kind of risk is a potential for sedation. They're otherwise fairly well tolerated, they work quicker, have shorter half-lives, anywhere from four to six hours, where they don't stay in your system as long. That's sometimes helpful for certain people where you don't necessarily want extended exposure for the patient. They really work on the Alpha-2 receptor centrally in the brain and they regulate norepinephrine, or what we commonly call adrenaline, in the brain to modulate that. There is some small Alpha-1 effect, it's another receptor that's implicated in aggression. When we use these medications, you're really targeting those areas.

Typically when I use these medications, I use them for youth that have a history of ADHD or maybe generally just have more impulsivity or attention difficulties, we'll use it as an adjunct medication in the management of delirium. We use it for folks that are going through opiate withdrawal in symptom management. We will also use it with folks that have a lot of anxiety because it kind of just reduces that sympathetic response that kids with anxiety have or kids with a history of psychological trauma.

We also use it in kids that have physical symptoms. We talked about sleep in the last podcast, and sleep regulation's important. It's actually a very effective agent to help with supporting sleep in youth that can tolerate it, and that can mitigate aggression. It's also used as an adjunct for pain management. There's some literature in the pain world that suggests that it can really help augment other pain strategies.

I really like the Alpha-2s because of the diversity of uses as well as the limited side-effect profile. What I will say though is if the severity of the aggression's pretty high, I've not seen it be as effective. It can be delivered as a patch, which is another advantage. There are liquid formulations of clonidine. There's a variety of different ways you can deliver it, too, but just a useful medication to be familiar with.

Then the antihistamines can be very helpful with anxiety, can be helpful with sleep, can be helpful with just mild levels of distress. Typically if we use them, we use them in folks that may be more medically fragile but not at risk for delirium. Some of our individuals with eating disorders may actually benefit because it helps with some of the anxiety around eating and the associated agitation or even aggression that they may have when they're distressed. It actually can help a little bit with GI discomfort. It has some antiemetic effect. It can be helpful for sleep regulation in some folks. There's just folks who come in where they tell us that they've used it before and it's helpful for a variety of indications.

Things we need to be mindful of, they can be sedating agents. They can also have that paradoxical reaction like benzodiazepines. I've seen that most commonly in individuals with in touch with disability or autism where they actually become more agitated when they get those medications. They also can be deleterious in patients who are delirious. They have some anticholinergic properties that can actually make delirium worse.

Dr. Heidi Burns:

Dr. Malas, you mentioned the use of Alpha-2s and hydroxyzine in the case of managing sleep. Are there other agents that you like to use or that you'd recommend using for help with patients who are struggling to sleep?

Dr. Nasuh Malas:

It's really interesting, because as a consult psychiatrist, one of the really exciting things that I get to experience is how people can see the value of psychiatry in the medical setting. One thing that we can be very mindful of, not only in psychiatry but in general in the care of youth that have concurrent physical symptoms or other physical complaints, is how we can utilize our medications to manage multiple target symptoms. Sleep is one of them. Another one that we oftentimes are thinking about is pain, appetite, nausea. When I'm thinking about the patient, I'm thinking about their whole experience: physical, emotional, cognitive, social, and thinking about a medication that can target the most needs for the patient with the least amount of side effect.

In terms of sleep agents, there are some more traditional sleep agents. One that we typically use quite frequently is melatonin, largely because the side effect profile is very limited. The only side effect that I have really heard from patients is they may occasionally have some more vivid dreams, but typically is otherwise well tolerated. It can be obtained over the counter. The issue with melatonin is it really is only helpful for sleep initiation and there's a large cohort of patients that don't respond to melatonin.

Another medication that you may actually see a psychiatrist prescribe is Trazodone. Trazodone is a medication that was initially developed to assist with depression. It didn't really work for depression, but looking at symptom scores from patients taking Trazodone, it was identified that sleep actually improved in that patient population. It has now been used primarily as a sleep aid. It's one of the most common sleep aids. Things to be aware of with Trazodone is it can prolong that QT interval that we talked about before, as well as can cause a very rare side effect in boys called priapism. Just need to be mindful of those things, but generally pretty well tolerated. It can help with both sleep initiation and management. There's a wide dosing range and a lot of patients will find it helpful.

In addition, there are other medications that we will use in certain circumstances. We talked about the Alpha-2 and the antihistamines. Sometimes we'll use a medication called Cyproheptadine. Not commonly as much with psychiatrists, but other specialists may use it. It has some sedating properties. It is an antihistamine, but it is a potent appetite stimulant. It also helps with headaches and as well as abdominal pain in folks that have functional abdominal pain picture. Cyproheptadine can be helpful. Sometimes we use other kind of sleep agents that are specifically designed for sleep, less so in kids, but agents like Ambien or Zolpidem can be used, but we typically try to not use it because it can create some difficulties with parasomnias and other sleep-related issues and can be habit forming.

There's a variety of agents we can use. One thing I would caution is there is a practice sometimes of using neuroleptics or antipsychotics primarily for sleep. I would really caution against that because of the risk benefit profile of that medication and there are better alternatives. But ultimately I think it's about using agents that clearly can aid with sleep, but then thinking about the whole patient, and how you may be able to treat other factors that may be contributing to the sleep at the same time.

Syma Khan:

Dr. Malas, would you like to just elaborate a little bit about why managing sleep and agitation management are kind of intertwined and kind of the importance of that

Dr. Nasuh Malas:

Again, I think it goes back to what we talked about on the last podcast that we're looking for any factors that are contributing to that multifactorial presentation of aggression. There's a saying that we had when I used to work in the emergency room at a different health system where a turkey sandwich may be better than giving a medication. Factors like hunger, like pain, like sleep difficulties, and then just factors related to frustration with the stay or sensory factors, those may be the main antagonist towards somebody staying calm. Thinking about those factors and addressing them proactively can minimize the use of medications overall.

I'm also a big proponent of using the least amount of medication to achieve the highest-yield benefit. We don't want to just do isolated symptom management, we want to be thinking about the whole patient, what's their needs globally, not in isolation. I think the difference between effectively managing aggression and being ineffective is when we're just thinking about the aggression in isolation. If we can think about it globally, I think we will deliver pharmacology that is much more customized to the patient's need.

Dr. Christina Cwynar:

Dr. Malas, I really appreciate you reminding us to look at that entire picture. I think we talked about this scenario during the last episode where we often have these young people coming in and agitation has been chronic and these families are exhausted. I also like to remind care providers that parents too need to be cared for so that they can better care for these kids, and maybe they need a sandwich before they can sit down and have an in-depth conversation with us about what's been going on, what's been working, what's not. I mean, I don't know how many parents we've sat down with and it's like, "When's the last time you ate?" "Oh, it was 12 hours ago." "Okay, let's get you some food and then let's sit and talk about what's going on and how we can be helpful."

I guess let's start wrapping up and see if there's anything else anybody wants to put towards our audience.

Dr. Nasuh Malas:

Well, Christina, I just wanted to highlight what you just said, which I think is really, really important. Aggression is not just about the patient, it affects everybody who's involved with that patient's life: the school sports, families, other providers, the PCP, and so being able to understand the context in which that aggression's presenting will also make you more effective in delivering that care. A lot of times the stress on families is tremendous. It can create burnout, it can create very strong responses at times from parents where they can either become very avoidant or they can become overly involved where they're on guard all the time or anticipating bad things happening and it can create a traumatic response in the families. It can create a lot of mistrust with the health system. We've had families who come in who have certain rules that they need to follow or their kids need to follow, and if we deviate from that rule, that the families get quite distressed.

It's just really important to understand that experience and attend to the family and the support system for that child. Because if we can help that support system, we can provide further guidance and partner with those caregivers and other supports. It creates more safety, more structure, more calm. We know that for any child regard, regardless of the reason that they're distressed or agitated or aggressive, if their support system is calm and structured and feels safe, that helps them regulate themselves. If that support system is distressed, stretched, chaotic, that's going to make the aggression worse. And so, I think it was beautifully said, you really need to be mindful of that and not think about the aggression in the child just as the child being aggressive, but as a system that is stressed.

Syma Khan:

I think it just reflects on that point about safety, focusing on the safety of the child, the family, and the care team as well that's providing that care, and kind of how can we collaborate using pharmacological and on pharmacological methods to support them.

Dr. Christina Cwynar

Well, this has been a very dense episode. I just want to remind everybody listening that we have really just hit the tip of the iceberg in talking about medications that can be used for the management of agitation. Dr. Malas, we thank you for joining us today and sharing your time and your expertise. Thank you to everybody who has tuned in. Nurses, social workers and physicians can claim CMEs and CEs at uofmhealth.org/breakingdownmentalhealth. You're able to do this anytime within three years of the initial air date.

I hope you join us next time.