Chapters Transcript Medical Management of Autism and Associated Symptoms Gregory Cejas, MD, discusses the modality of treatment which depends on upon type, severity, frequency and setting. My topic of present today is on medical management, uh of autism and associated symptoms. So, uh I stated my name is Greg Seja. I am a child psychiatrist here at Washington University. Uh I'm one of the directors for Autism Clinical Center. Uh And I also uh run our Fragile Clinic as well, which is a decidedly smaller kind of uh uh function of that clinic. Um I think this would be a good topic to cover today because uh not just because it's my day job really. Uh but also, you know, I think in serving in this role, uh I think we've become very aware uh of all the challenges that come with, uh not just in Illinois, but even in Missouri, uh getting kids the care that they need, uh when it comes to uh their behaviors, which can often be very challenging for families, schools, uh and our health systems alike. Uh So in that role, uh we try, uh to, you know, get things started that will hopefully help. Uh But we recognize that a lot of the times, uh you all are trying to find folks who are able to uh see these patients, uh, and it's really hard to come by or there's a long wait. Uh, and so my thought with this would be to share what I think about when I think about these, uh, really challenging behaviors, where do I start? Uh, not just even from medication standpoint, but we'll get to that piece too. Uh, but how do I categorize it? How do I think about it? How do I go about, uh, uh, navigating, uh, sometimes really challenging stories, uh, to try to get the best way for me to realize or figure out where these behaviors are coming from. Because I think that's one of the most important things that we need to, uh, figure out when we encounter these behaviors. Uh, so that's part of this. But then also, I think, uh, I think it will be helpful to know, you know, even if there's medications on here that are not gonna be ones that I would recommend you start cosine. For example, I would say it's probably not one that I would recommend most pediatricians go ahead and start with folks. But I think it would be helpful for you all to kind of get a sense of, you know, if you have patients who ultimately get into these offices where, you know, we kind of take care of some of these really challenging behaviors, what we're getting into 2nd, 3rd, 4th line kinds of symptoms. Uh, do you have a sense of why somebody might be choosing those medications was the evidence behind that. Uh, but then also, you know, what can I as a pediatrician sort of track, uh, in terms of, uh, you know, other things that might come with that? Really? Uh, so that's my goal and hopefully we'll even have time here, uh, for questions that I can hopefully answer as well. So I have no relevant disclosures again. I, I am a, uh, a researcher with the Fragile Clinic. We have a small uh study that isn't really relevant to the topic. Uh We don't have while many patients have Fragile x syndrome, uh we have autism and vice versa. Uh The studies I reference uh for these medications and treatments uh do not uh go for that group specifically, but I'll just mention that at the top here as well. So I like to start by just mentioning what is aggression and, and in some ways, it seems obvious at first, I think we have no aggression when we see it, but I think it's really important to break it down because uh to me there are sort of levels to it and those levels tell you different things both in terms of what, you know, parents are facing, but also severity levels, uh what's happening in the moment really? I think that's really important at space. There's, you know, verbal aggression, I would say it's kind of the lowest form of aggression and that can be uh not just cussing or threatening as you might think it can be, you know, a child who is non verbal, just sort of engaging in more aggressive sorts of, of vocalizations, more yelling, uh, more grunting or growling kinds of behaviors. The next level is auto aggression. So, aggression towards the self, uh, head banging, uh hitting ourselves in the head, uh hitting our arms against the fall of the forward dropping. Uh All those behaviors would kind of be a part of that then moving to aggression towards property which is throwing things uh uh not necessarily at people just throwing things around the house, uh tipping over couches, tables, uh punching holes in walls, breaking glasses, things like that. And the final and most severe, typically speaking uh is aggression towards others. Uh This is where aggression uh goes towards those in the household towards teachers, supports uh those in the community. Essentially. I really like the use of uh the MOAs scale. That's the modified over digression scale. It's a clinical scale that uh we use often to kind of get us assessment of these areas. Uh And it breaks it down really nicely into these four subgroups which I find really helpful because as we get into uh this discussion in this presentation, it's really important to get a sense of not just is aggression happening, but what's coming with that? What does that look like? Uh getting into the specifics really helps me to know when do I need to think about initiating treatment? And if so what treatment do I need to go? Not just from a medication standpoint, but from a behavioral intervention standpoint, I sort of encapsulate all of this into, you need to define not just the type like we just mentioned, uh we need to define things like severity, uh the frequency and the setting that these behaviors come up in. And I'm gonna focus most of my talk on aggressive symptoms because it's the one that parents frankly are most vocal about. They're the ones that tend to draw the most kinds of providers into the home. Uh, and to get all hands on deck in general, we, we'll address other, you know, psychiatric mobilities as well. Um, but I think it's really important with aggression specifically to define this because as we're about to get into here, uh, aggression is, you know, a, a downstream problem, a final common pathway, uh, of a variety of, of potential, uh, uh, upstream feeds, right? Uh, we'll get to do the other ones here specifically. But I think defining those in these four things, that's the type of severity frequency and setting helps me to know what's my trigger point. And for what if I have really severe behaviors, but they only happen once every six months or once every three months with a really clear identifiable trigger. I may not be likely to really start a medication for that while it's really severe in the moment, you have to weigh the risks and benefits of that medication, uh, for the individual and what that can carry. Uh, whereas if I have maybe a moderate level of aggression, but it's happening multiple times a day, it's very disruptive. It's only their ability to stay in school or to learn that environment to be at home, to get good sleep. All things that we know can help behaviors. I'm more likely to, you know, initiate a medication for that. Uh Even though the severity of that uh uh uh behavior is less similarly with the setting, right? If I'm only seeing this in one setting, that's telling me more so that there's something in whichever setting that's uh this behavior is occurring in that we can maybe modify to, uh that, that be through accommodations or otherwise, uh to see if we can avoid, you know, using a medication overall in general. Right. We have a lot of parents where they'll tell us they do just fine at home. It's really when they're at school and doing sort of non work where we see the issues or vice versa. The school has a really good amount of structure that the child thrives in. But at home there isn't that structure and that's where the behavior starts to come in. I'm less inclined to say, well, we need to sort of medication now uh in those situations and may be more inclined to say, well, let's see if we can get ABC B A behavior analyst involved uh through the school or otherwise, to see if we can better address those elements first and see what changes as I mentioned before, that sort of downstream issue, right? Those are really important pieces. But aggression is communicating something I mentioned, communication deficits could be one reason uh for why we might have aggression uh in the first place. But I think even beyond that, aggression is telling you something, but all behavior is telling you something is a form of communication. It's down to you as a pediatrician and, and for parents to determine what is it that's trying to be uh trying to tell you, is this a child who is trying to tell you that their stomach hurts, right? Uh That they have headaches that they have really bad uh constipation and we just can't have a good way of telling anybody otherwise. Uh until we figure those things out, uh that could be one reason or one thing that the child is trying to communicate, it may just be frustrated because we're trying to tell them, tell somebody what they need and they can't figure out a way to do that. So is there a accommodation uh communication device, a text board, uh something that we can do to help with that communication gap that would alleviate those symptoms behavior? Is there pain we're missing? Are there sensory issues that we can accommodate for, uh, all of these things are pathways to an aggressive behavior that the child could try to communicate with, uh, that don't involve, or maybe would minimally involve, uh, psychiatric medications to address these behaviors. Then of course, there are psychiatric comorbidities which we know are really common. Uh, anywhere any of the study you look at, uh, between 40 to 60% of patients with autism, I tend to say somewhere between 4050 can have a psychiatric comorbidity. Uh So these things happen all the time, but certainly it's not every single patient. So there are certainly times where it's appropriate to say this is a time where you need medication, this is uh uh uh appropriate to do so. But there may be other times when you need to explore other symptoms. And what I usually recommend is especially for kiddos who have a hard time communicating uh verbally. But even beyond that, it's really important to gather information from reliable sources that can include uh parents most obviously, but it can also include caregivers, right? If there's somebody in the home helping them out, there's grandma who's there frequently. Is there an in home aid? Is there ABC B A therapist in ot who works this child often get information from them if you can get it released from them, if you can to see what their thoughts are. Same thing with the schools, right? Especially in our rural communities, the schools are doing a lot of the heavy lifting from a behavioral standpoint and they're gonna have folks hopefully who know these kids well and can sort of help to uh fully flesh out the picture uh especially in the times where maybe the family is really, really distressed and having a really hard time sort of giving you all these fine details that we really know and love. Uh It's important to get as full of a picture as you can fully acknowledging that you guys have a 30 minute visit uh for a lot of these times or a well, child check where you're asking other things. Uh But this helps us to know when do I need to go for medication versus when do I try to, again, acknowledging that there's a hard time finding B CBS everywhere. When can I try to address things from a behavior standpoint, lt standpoint, from a speech standpoint, et cetera. So when I get into medications, I, as I mentioned before, and I kind of get past this relatively quickly since I already sort of addressed it. Uh I consider medications when the aggression is severe if it's not adequately treated with behavioral interventions. If I have BC bas working with the family, R BT is working with the family and we're still having behaviors if it's incredibly frequent. Really? Is it disruptive for their daily life in a way that isn't modifiable or hasn't been modified? Uh by, uh, behavioral therapies they've offered, that's when I'll sort of consider these steps, medications can be used for progression, right. But importantly, studies have shown they're not gonna change the, the autism symptoms overall, right? They might attenuate the, uh, uh, kind of big, uh, explosive behaviors that will come. But typically speaking, not going to change the sort of rigid thought, um, social communication deficits, things like that, that we also know occur, um, in these kiddos in these adolescent. So, you know, I think appropriate expectations, uh, are needed both for providers. But also when you're talking about uh, these medications to families to tell them, right. This is for the aggression. We, we have other things we need to do. We need to get you guys hooked in with resource wise to better help, uh, uh with these behaviors and with the autism itself. And lastly, there is, uh a fair bit of research at this point that suggests that, uh, you know, if not half or more, uh, of our patients with autism who have behavioral concerns, who have medications on board will be drug refractory, which for us means really two plus medications, essentially that's more likely to occur, uh, with patients with intellectual disability, uh, in males and uh older, uh individuals as well as they get older. Um, and with that means there's a lot more risk of polypharmacy. And so for me, as a psychiatrist, I'm always thinking about well, is there a medication I can take away. Is it something I can add? How do I complement these medications together? You, you know, take medicines that I know will work well together. But also acknowledging there are times where I might have to do more and then being really conscientious of, I need to make sure that I'm checking interactions. I am, uh, if the pediatrician is starting new medications because a lot of these kids have medical needs as well. Uh, making sure I, I'm checking in with the families frequently to see if there's new medical things that come up on the pedia pediatrics. End of things I would do the inverse, you know, you're treating the, all the medical needs of these kiddos. You may also be doing some behavior management too. Uh, but I'm thinking about certain medications for a variety of the medical needs that these kids can present with. Uh, I'm plugging these medicines into the, uh, you know, up to date, uh, uh, interaction, uh, machine basically to make sure that what I'm doing isn't causing problems with the psychiatric medications they have on board. And if they are, I'm either modifying what I'm doing from behavior standpoint, uh, uh, management standpoint or I'm reaching out to the psychiatrist to kind of discuss what can we maybe do differently or what should they be thinking about? What should I be thinking about to make sure that we're not missing things we're putting kids in harm's way. So I'm gonna start talking about medication specifically and ones that I typically think of first, uh, in the management of these, uh, uh, behaviors, uh, ones that I use most commonly, ones that you guys probably use most commonly. And then I'll talk about other, uh, medications you might see on the list and I'll give the caveat, there are some medicines on here that I, I don't expect you to use. Right. If you're getting to the point where you're considering lithium, my guess is that I would or my hope would be, uh, if you're not already, you're thinking about, uh, putting a referral to see a psychiatrist who's more comfortable using those kinds of medicines. But these ones, especially here at the start and I'll sort of tell you the delineation point for me where I'd be thinking, ok, if you haven't already been trying to do this on your own and sort of steward resources, uh, which I know we appreciate and you guys try to do your best with as well. Um, I'll try to kind of give you a branch point of where I would say if you haven't yet put in a referral for someone, uh, to, to sort of help manage these behaviors. Uh, but the neuroleptic medications, the antipsychotics, uh, are the ones that I think most commonly get used, I would say. And the reason for it is because of the FDA approval for two medications within that class. And that's for a prazole which is Abilify and risperiDONE, which is Risper, uh, RisperDAL. And I think the first thing I state with that is that, you know, just because a vilifying spirit and are the two we have FDA approved, does that mean that there are only two medications in that class, uh, that can be used for these kiddos, uh, for these behaviors? It also doesn't mean that these are the medications I go to first and I'll kind of get into that in the next couple of slides about where I sort of think of starting with these versus maybe another medication like an alpha agonist or a stimulant or a neces. I essentially, uh, so more on that to come. But I'll start by just saying you don't have to use these two just because they have the FDA approval. I think the other part of that DD approval for is that they, they're not FDA approved for the management of autism. They are FDA approved for the management of aggression and autism. And again, what the, uh, uh, studies have shown which I referenced. Doctor Maris Natasha Marris, who, uh, you may have heard of or seen or heard, talks about who is also at Washington University and does a lot of research with these kids. Uh, you don't or you shouldn't expect, uh, changes in the core autistic symptom burden, uh, with the use of these medications. But there is a very solid evidence base to suggest they can be very helpful for kids who have severe aggressive behaviors. Abilify has a range anywhere between 1 to 30 mg, re Spiridon up to six. If you are starting to inch above, you know, 10 or 15 mg, I might be thinking about getting him in with a psychiatrist because or in the case of re Spiridon, you're getting above, you know, three or so milligrams, I'd be thinking the same thing because the higher the you go into doses, the more likely it is you're gonna uh develop other side effects or put kids at risk of other side effects. Most common ones tend to be things like G I upset drooling, increasing appetite and weight gain. Uh A lot of folks have the idea that, you know, uh Abilify is marketed as basically the a weight neutral uh antipsychotic. I can tell you my experience that is a relative term and I'm not sure that uh our studies necessarily capture that. At least the the headlining ones. I don't necessarily capture the risk that there is still uh of substantial weight gain quite frankly with Abilify. I would say it is less likely to occur compared to risperiDONE, but just because it's marketed as sort of the one that you do because it has less weight gain. Uh I would not take that to believe that this may not come with any weight gain. So I'm always still counseling patients that in families, uh, that, that is a risk of and that can be really, really substantial. Uh, for me, it's often a grounds to switch between. I view risperiDONE as the stronger option. Typically when it comes to, if you have more severe behaviors, I tend to find that it has a bit more substantial of an effect, but it has a higher risk compared to Abilify of the weight gain of some of the EPS side effects. Those are things like dystonic, dystonia or dystonic reactions. Uh Those are things uh like akia uh which is sort of that restlessness that people can feel and especially with hyper proact anemia, which is really unique to risperiDONE. Uh uh as opposed to Abilify, it can happen with Abilify but much, much less risk. Um But those are all notable side effects that are less common than G I upset are truly increased appetite and weight gain but are uh substantial. And I talk about and counsel families with, I also bring up uh uh tardive dyskinesia, which is of course, the longer uh uh serious side effect that can come typically after decades, as opposed to uh you know, a year or two and typically at higher doses over that period of time, uh a higher cumulative dose uh increases that risk compared to a lower one. But I'm still bringing it up to the parents to say, hey, this is something that can happen later on I mentioned that this is something that still was really helpful for these kids and that I typically still recommend but that we check on these things, we monitor these things. Um What I do in my practice is the abnormal uh voluntary movement scale or the aims, which is a really quick and easy uh five minute test. I do that, you know, at least every year, sometimes six months if I'm on a really high dose of medication that I know that kids have been on for a long time. Um, basically say, well, if there's anything that I should be looking out for, from a dystonia perspective, any sort of tardive movements, more sort of jumpy, uh, quick darting movements of the tongue or the fingers. That would be more concerning for those because if you catch it, they are reversible. Uh, it's when you don't catch it and they're going on for a long time where that becomes more problem. And of course, if you are seeing those symptoms, there will be time to refer to a psychiatrist as well. Um, but in general, I'm also monitoring lipid panels. I'm monitoring weight cholesterol blood sugar overall because we know these are medications that increase metabolic syndrome, uh, risk a slight reference. Uh This is a meta analysis of Respert in Abilify as you can see. Uh, most here fall into, uh, uh very helpful. So these are really well known well used medications. Again, there are other medicines that we know have use in this population. I'm not expecting you to use closet pain. There's a lot that comes with that. You should be referring to a psychiatrist, but I make note of it here because if you see this, it does not mean that the child that you were working with has schizophrenia. It may, uh, especially in the older teens. Right. Uh, but there is some, uh, small evidence, small because we just haven't tested this net bigger populations. It suggested it's very useful for those who have failed basically initial treatment with the antipsychotics that are more common to have less risks. So don't just assume that somebody has schizophrenia with that, that I would communicate with the psychiatrist, just ask about those things if you see it. Uh But know that the psychiatrists having to sort of follow the white blood cell counts at least monthly if they're on for a long time and more frequent than that if they're on it for less than a year. Uh And you know, there are other things that you can come with that. That's not just uh uh the uh decrease in white blood cells and decrease in neutrophils. That's the most scary one that people probably know about from medical school. The myocarditis is also very, very uh common. It's just as common as uh the, the uh blood cell count drop. I shouldn't say very, very common. It's still for a side effect. But it's a really scary one that's a relatively common relative to other big scary ones we have for these medications. So, as pediatricians, if you are seeing a child coming in with, uh, you know, concerns for chest pain, things like that and they on cause pain, I might have a lower threshold for doing more work up within that. So I mentioned again, those are the medications that are approved vilify Barone specifically, I often, especially in the younger kids will start with an alpha agonist. You all probably know alpha agonists, uh guac and quant, especially for the uh treatment management of a DH D. Uh Even though we always know that they are initially kind of started as blood pressure medications, we just use them really well and they work really well uh in our kiddos, uh with a DH D in combination or standing alone uh with stimulants. Uh but we use them or I use them uh in kiddos who have autism, especially in the early ages, but certainly in the older kids who either as a first line when I feel like the behaviors or the symptoms aren't terribly severe, but they're very frequent and still disrupt to their day because the way the risk profile is still relatively low, the most common things with the guac tend to be sedation, dizziness and of course potos static hypertension that's most prominent with uh quantity as opposed to guan fishing, it can happen in both, I tend to think of quant as a heavier hitter. Uh It's more often caveats aside, uh more often more acidity than Guan fishing in my experience. But individual responses may vary within that, but both are really good options. Squad 15. Of course, I usually start as the immediate release twice daily in the younger kiddos and making sure they tolerate that before I would convert over to intuitive, which is the extended release. Uh I also will use the immediate release versions of that medication for those who uh can't swallow pills because you can crush the immediate release version, you can't crush uh the extended release version that also holds true with quantity. The other thing to watch out for Roon of course, is the rebound hypertension, which is more notable and that monic scene so don't abruptly stop it. If you are using that medication, try to taper off of it. If you can't, then there's stimulants and I use stimulants in a couple different cases, predominantly when I think there is a DH D going on. And when I say when I think A HG is going on, I am still assessing for a DH D the way it typically would, which means I am getting parent report and I'm getting teacher report and I'm getting that through Vanderbilt assessments uh in both settings essentially. Uh And as if they fall into sort of that bucket, that's when I'm sort of considering stimulants we all know ad G is hard to diagnose in kids with autism, especially the inattentive type. It's very hard to kind of go chicken or the egg in terms of what are inattentive symptoms versus what are, uh, uh sort of fixations on things that aren't what I need to be fixating on essentially. Um, but it's more over and I especially consider these more. So, uh for those who we have a pretty clear indication that they're struggling in school, either because of tension or because of hyperactivity or impulsivity. The note here is that these medications are still effective stimulus are the most effective medication. By far in the people of psychiatry, uh you can expect an 80% positive response rate in neurotypical peers, uh that drops to 50 to 70% in those with autism and HD. And we think the reason for that is because a lot of these kids have a hard time tolerating higher medication doses. Uh, they have experience more side effects with those medications and that can include headaches. Uh, that can include G I upset, uh that include decreasing uh intake of, uh just orally overall. Uh And so because of that, you can also get besides just lower doses and lower max doses. Uh, a lot of discontinuation, basically lack of toleration of those side effects. In general. I've already mentioned the most common side effects. Um, you know, one thing in general I think about with stimulants is that there's the old sort of uh uh logic of all these medications are going to decrease your child's height. We found with more recent papers, meta analysis is that if it does affect height somewhere along the lines of maybe a centimeter and more likely, uh, there have been a pretty strong me analysis that suggests it may do more to decrease sort of the trajectory or slow the rate of height, uh attainment uh the growth velocity. Um but they should end up where they usually would have been so pretty modest and somewhat overstated, in my opinion. Um The more serious side effects obviously are heart arrhythmias or cardiac events. If you have a child who has a history of heart issues in an early age or if there's a family history of early heart issues. So in their teens, essentially, um I'm getting an EKG before I would start these medications, but most of the time you don't need to go that step. But of course, you're monitoring blood pressure, you're monitoring weight and growth charts to make sure that intake is uh still adequate. If it's not considered a dietitian or ot referral here at children's hospital, we do have a complex reading clinic, but I think it's a really great job uh with these kids and addressing both sensory needs that these kids have uh when it comes to increasing sort of dietary variety. Uh but also some of the motor mechanical aspects of things through a speech therapist as well, then there's antidepressants and anti anxiety medications. Uh So the I reference specifically as psoriasis here because the majority of the research we have in the autism population is with these medications. Not because I have any doubts that SNRIs may work too. I frequently use SNRIs uh for kids who don't respond to uh 1 to 2 Ssris depending on the case. Or if I know a parent has a good response to this. For example, they thought useful, obviously, if you noticed or thought about it in anti anxiety, sort of uh or a G ad generalized anxiety kind of clinical picture that's very obvious. But there is some data to suggest that for those who have a very perseverative ruminative sort of thought process, they get stuck on one thing and can't move past. It almost seems more like O CD. Again, these things are really hard to sort of diagnostically suss out. Um But there is some evidence that thought that these medications may help with those kinds of symptoms. And a lot of experts in this field uh have used these medications for those purposes. The most common side effects can be stomach upset, weight gain, uh headaches, you can decrease libido, it can lead to uh the other sexual side effects. Um especially the higher doses I worry about especially inside the younger kids. Uh behavioral activation. You know, a lot of people were worried when I, what I, what I mean by that, I'll backtrack what I mean by behavioral activation is really just an increase in sort of, uh, agitation, restlessness, uh, pacing just seeming more irritable overall and more energetic. It's different than mania or inducing hypomania, but it's not too far off. And just because a child experiences that would necessary does not mean that they are at increased risk of bipolar disorder, but they have bipolar disorder, all of those things, right? Um That's an important caveat. What it means for me is either one, it was too early to try to depress the medication that they were just too small to be able to tolerate or two if they're an older kid. Oh, that this just wasn't the right one basically, but I might try a second one of a different class or type essentially uh in those instances. And if it happens again, maybe then I'm more concerned. And again, that would be a time where I would say maybe a psychiatrist needs to evaluate if this is a potential, you know, a mask of mania versus just behavior activations with area I referenced this Cochran review which I think is uh I really like, I love Cochrane reviews. I'm sure you all do too in various other fields. Um But I like this one because there's just really not a lot of information, not all the studies on this medication class uh in patients with autism, but they did find nine studies, five in Children, four adults, not enough to have a meta analysis, but enough to sort of look at and review, uh, what those results showed what they found was, there was not much benefit seen in kids, but there were still, uh, some benefits seen in adults who use these medications. They specifically looked at a few, uh, fur which is less commonly used FLUoxetine and PROzac, which is very commonly used FLUoxetine, which is lub box also fairly common. And then Cytopan or CeleXA, uh which is very similar structurally to Lexapro, uh or eal. Um, initially, when I read this, I was a little disheartened, uh because I think we, we try to use these often. Uh, but as you can see that the, the sort of study results are, are relatively dibbling. Uh I did see a talk though from one of the authors of one of these studies in Children, uh at a national conference and he talked about this in the negative result and said, well, you know, certainly there are negative results in every study or in every kind of study. Um, but he sort of alluded to the fact that this is a really hard area to really generate, I would say good quality consensus in terms of benefit versus no benefit of these medications. And what he mentioned is that you have to think about the heterogeneity of this population, not just in sort of adaptive functioning level, intellectual capacity, verbal functioning, but also those things, but also in how anxious symptoms can present and how is this looking like? You know, is this anxiety versus more stimulating our stimulation, more motor stereo, these more perseveration that's not really related to an anxious process because you wouldn't expect those to necessarily respond as well uh to an SSR I as you would, those that are more clear, clearly related to an anxious process. Um He shared, you know, despite this, he's, he still uses medications uh like uh Ssris, Citalopram, et cetera uh and has found benefit and I'll share that I, I've had my fair share of plenty of kiddos who have had a positive response to an SSR I but it is not by any means 100% even if you have an adult or a child who has depression anxiety uh without autism, uh the response rate to Ssris tend to be something along the lines of 25 to 30% uh with each pass of those. Um So these are not by any means, uh always going to work every single time. But I, I had that conversation with families to say that this may help. It may not, it can become pretty clear, but I would not expect to see results with for a good 6 to 8 weeks. Uh especially when it's more anxiety as opposed to depression uh symptoms, which tend that I find take a little longer than the 4 to 6 weeks that we've all kind of come to expect compared to depression. It's a cut off, uh uh uh uh table. Unfortunately, some of our reference mood stabilizers, but we'll go relatively quickly and I'm referencing these because what I want you to know if you see these, these are not necessarily mean that the child has bipolar disorder does not necessarily have uh mania or things like that. They may but still holds true even the autistic population, this is true for the neurotypical population as well. The risk of childhood bipolar disorder uh is still relatively rare, right? Um, when I tend to see it happen is when you have a huge genetic load where you have multiple family members who all have had bipolar disorder, uh that might prime the pump. So to say, uh for an early presentation of that, the same thing is true for psychosis. Uh I don't expect to see, uh, a 10 year old with bipolar disorder, for example, right? Um, certainly if it looks uh episodic and contained within weeks and it looks like, uh, uh mania, that's one thing, but just because you have an increased activity that's sustained time, does that mean you have uh, uh mania per se? But you might see these otherwise use a sort of 2nd, 3rd lines when those initial approaches with the lower risk medications aren't working. And for you as pediatricians, if you are starting to think about using mood stabilizers. To me that's an indication of, if I haven't already, I'm putting a referral in because they come with a lot of issues. Um some more manageable than others. Uh Two big ones that we'll see that have I find a fair bit of issues that work often quite well are lithium and devico lithium does not necessarily have a lot of uh scientific evidence despite being around for the better part of almost a century at this point. Uh But there are several case series and retrospective studies that have shown some benefit uh for basically patients who have really significant aggression that does not respond uh to an anti psychotic one. Um you dose it twice daily. The big things to watch out for are kidney and thyroid effects. Um Almost every single time if you have a thyroid that's functional on the lithium for long enough that thyroid is going away. Um kidney issues tend to be a longer term issue um on the matter of decades plus. Uh but really that psychiatrist should be checking, you know, basically renal clearances, GFRs, uh B and creatinine et cetera at least annually if you're on uh lithium. And maybe more frequently if you're on for a long time, you're always gonna be monitoring uh thyroid levels, uh things like that uh as well in the long term. But you guys as uh uh pediatricians should be aware of if your kid is on lithium having a higher vers blood check if you're ha hearing symptoms, um, increasing nighttime, uh uh urination can be a very common issue with lithium and a and a sort of a red flag for kidney issues. Uh So I would just have a quicker trigger to kind of check on those things. And again, talk about that with uh your psychiatrist that you're working with. Uh for your kiddo. There are several studies that show devico can be helpful. Um confounded a little bit because of high placebo response rates. Uh With that, that's true of almost every single psych psychiatric study as well. So I don't get too bogged down that. And again, with the heterogeneity of this group, um you know, results may vary to some degree. Uh But again, if you see that it does not necessarily mean they had bipolar disorder, I tend to not use decode as much as or as frequently as I use lithium one. I find lithium to be more helpful when I use it compared to Depakote. But I also find de could be really hard to tolerate for a lot of folks. Um There's the weight gain concerns for the girls PC OS is a really big and important thing that people can struggle with. It's obviously very hard uh easy on your liver if you have a lot of uh other medical things going on as a lot of kids who have genetic conditions and autism do. Uh it interacts with a number of medications and can also have, uh, uh, a lot of the, uh, liver enzyme elevations, transaminitis or transit. Yes, transom. Uh, as well. Addition to sedation. Right. It's a messy medication. So I try to use lithium more than I use Depakote as a pediatrician. I'm just gonna be aware of, if I see that on the med list, I should be checking interactions and I should be talking with uh that provider more to make sure we're on the same page in terms of the medications and we need to go limiting pi pharmacy limit interactions when we can and sort of working synergistically when we can is next to have more limited evidence I would say in this population, but in my opinion, have less sort of worrisome uh uh concerns as homo and ox car baze pain, both have uh quite frankly, very scary but uh quite rare uh uh side effects of Stevens Johnson syndrome or 10 as well. Uh which is the uh uh uh really, really serious skin infections that can be fatal. Uh That will avoid those things the way you avoid those tend to be with slow, gradual uptitration, especially with gene that really mitigates that risk. Uh But I like both because relatively they have a less, I would say messy sort of interaction profiles, they aren't really strong inducers. Um They interact with less things, especially marogen. I find a lot less weight gain with that one, in particular, uh, Terazine has hyperemia as a risk. Uh, some drowsiness headaches are also common, can have weight gain too. But again, I tend to reach for those if I'm, if I'm as a psychiatrist and thinking about, well, my, uh, my antipsychotic hasn't worked that well. They're not responding that to al agonist. I might reach for oxen or Romo. Next, basically. Uh, so again, things to be aware of as a pediatrician. This is why they may be used if they don't have seizures. I also think of these medications for those who maybe have epilepsy as well. Uh, because there's, you know, even if their seizures are not active, uh, there may be underlying sort of sub threshold, uh, you know, pior activity that may respond well and may lead to less agitation, uh, with the use of these medications as well. Lastly, before we kind of go into questions, um, there are other sort of potpourri medications that you will find a smattering of evidence for that I think go either way. And, uh, but I think you will see them often. I use these in particular often when I'm either getting subthreshold responses with my other medications. Yeah, I'm getting, uh, good responses but not quite enough and I wanna boost things up. Uh, because these medications predominantly toys may be the exception here. Mostly these work quite well. Uh, in combination they don't cause a lot of, uh, uh, interactions uh they're pretty well tolerated and relatively low risk. So I think about these in those situations, now, trone you may recognize uh addiction medicine, basically. Uh, there is some evidence though, to suggest it can be helpful, especially in self injurious behavior. And in those who have hyperactivity with autism, that's not responding well to EHD medication management or that's, you know, again, some threshold in terms of, um, you still have symptoms, but maybe less than you did before with those medications. Um I tend to dose at the 50 mg standpoint because it's still pretty well tolerated. There is some evidence that suggests in the last few years that low doses may also be uh uh quite beneficial as well. Uh In my experience, I have found when I had good responses and I've had some really good responses for this medication. Uh It tends to be at that 50 mg threshold, especially in those with self injurious behavior. Again, a man is a uh anti Parkinson's medication. Uh There have been really only a couple of studies that look into this. Um, the best, uh one we had that had the most positive results was back in 2001 that showed a lot of clinic measure positivity less so with parent report. Um but specifically where they see the benefit is when it's combined with an anti psychotic, specifically riser on and especially when it comes to hyperactivity and irritability in that hate. We know, again, as sort of a headache, uh, seizure medication. Again, the best evidence for that tends to be with combination with her spirit down. Um, there is some caveat that there's, and then some thought that this medication can actually worsen some of the, uh, activity symptoms of a HD that's ongoing in my experience. That is not always the case but something I'm keeping in mind, uh, if I'm thinking about that medicine and lastly, there's neck which is an Ayal Cysteine. And this is really as you guys all probably know, it's an over the counter supplement, predominantly, you can get it prescribed as well. Um But there are several studies of weight that kind of come out very encouraging. It suggests that it can uh lead to really wonderful behavioral responses. I will tell you in my experience, I have not quite had that robust of a response. Um I've used it now, uh a few handfuls of times and I've maybe show seen modest benefit at that where I think the real benefit is it is a low hanging fruit is generally very well tarried. The big thing tends to be sedation or uh nausea with it. Um But you can dose it, you know, 600 mg once a day for a week, go up after a week to twice a day, up to, you know, 1800 mg three times a day or so and pretty well tolerated, pretty easy to manage. Um and if it helps, wonderfully, you've avoided the medication with even more serious side effects. Uh, so worth a try for some. But I will tell you in personal experience, I have not had that much success with it. These are my studies I've referenced. Uh and that's really my presentation. So I'll leave now with any questions anybody has. Created by Presenters Gregory Cejas, MD Pediatric Psychiatry View full profile
