All right. Let's go ahead and get started. I hope you don't have any difficulties today. Let me know if you can't hear me. I'm having some Comcast issues this morning, so we're working off a hotspot. Hope this works. I want to welcome everybody to AAP Virtual Didactics this morning. We are, as always, grateful for those of you who are on the front lines of the COVID-19 pandemic. We recognize that not all of us have shouldered this burden equally, so we appreciate those of you who have had a harder go, and please let us know if there's anything we can do to support you during this time. As always, we want to go through some of these goals. The purposes of this series are to augment didactic curricula that are ongoing at your home institutions, to offload overstretched faculty, to drive learning opportunities for off-schedule residents, and to develop more digital learning resources and support for psychiatrists in general during COVID-19. We're going to keep everybody video and audio muted except for our presenter. If you have any questions, if you click on participants at the top, you should see my name, Sterling Herring. I'm a PGY3 at Vanderbilt. You should see my name up near the top somewhere. You can double-click my name, send me a message, and I will present those questions to our lecturer at appropriate times. If you have any questions about the lecture series in general, concerns, suggestions, please feel free to reach out to Candice. Her email is there on the screen, or you can find her on Twitter. So without further ado, we're excited to have Dr. Mary Russell here with us from T.E.A.R. Memorial Hermann. Welcome, Dr. Russell. Thank you for joining us. Okay, I think I got myself off mute here, so let me know if you're having any issues on your end. I can hear you great. Okay, great. And now I can see. That's great. Okay, good. All right, so I'm going to talk today about neuropharmacology and rehabilitation. I am an assistant professor down here in Houston and work primarily out of Memorial Hermann up in the Woodlands tier there. So a couple disclosures. I am on the Speakers Bureau for Allergan as well as MERS. We'll not be talking about spasticity, so I can't foresee any conflicts. And some objectives of the lecture today is to understand what happens to the brain after brain injury, identify common neurobehavioral issues that are seen in brain injury, discuss common medications used and their side effect in brain injury medicine, to understand what medications are commonly used and their purposes and effects, and to understand treatment options used for education. I know that there was a previous lecture that was focused on mild TBI and for this purposes will be more moderate and severe TBI. Okay, so what happens to the brain after injury? So you get your primary insult, you get the primary damage and the mechanical damage, and then you also get a secondary insult. So there's a decrease in blood flow, some issues with metabolic disturbances, you can get the tissue ischemia, as well as you know with TBI is frequent to get the blood-brain barrier to be disrupted, which is why medications can have such a profound effect. And so you can also then that results in cytotoxic or vasogenic edema formation, inflammation, and the blood-brain barrier breakdown. So that's all phase one. Then as the damage kind of continues, you can get the axon terminal depolarization, release of excitatory neurotransmitters, free radical generation, apoptosis, necrosis, and all of those things can lead to cell death. And so what happens to the brain after injury? This is kind of a busy slide, kind of talking about, you know, similar to what the last slide I was talking about. And so, you know, initially after you have your injury, in the first couple of minutes you get an efflux of calcium and potassium, and then you get an initial surge of glucose because the brain is starved for it. And then after about 20 minutes and six hours, you actually start getting a decrease in glucose, so that metabolism is really kind of slowed down. And you get decreased cerebral blood flow for about seven to ten days after injury. And so this is just a PET scan showing a normal brain over on the right, and a mild head injury, and a severe head injury. So one thing that's interesting to note is that even with a mild head injury, you still get a significant impairment in the glucose metabolism. So what are we talking about when we talk about neurotransmitters and with the surges and the LULs? So you have your dopamine that comes out of your ventral tegmentum, your norepinephrine, which locus coeruleus, and then the projections kind of go throughout the brain. Your serotonin, which starts in the raphe nucleus, and then you get the projections that also go throughout the brain, as well as the acetylcholine, the nucleus basalis of Maynard, and then also GABA, and GABA is this green, dark green here, as you're kind of going on. So what I really like about all these projections is it kind of shows that even if one part of the brain is injured, it can still affect significant other portions. And so, you know, especially cognition, you know, all these areas, you know, the nucleus accumbens, motivational processes, but it can, you know, have an effect on a lot of other areas, and, you know, cognition is certainly not an island. And so, some common cognitive or behavioral symptoms that we see in brain injury are hypoarousal, agitation, impaired cognition, including impaired attention, apathy, or decreased initiation. In fact, we just have a patient now who, you know, wasn't really doing anything. Well, it turns out he was just so apathetic that, you know, once he got a little bit of stimulants in him, he's really kind of turned a corner. So even someone that looks like they're not tolerating, you know, can still potentially be a good rehab candidate. And as well as you can get anger, aggression, anxiety, depression, and of course memory impairments. Okay, so the generic approach to behavioral symptoms is first you want to rule out any reversible causes. So neurological hydrocephalus can be a big one. Hydrocephalus can cause apathy, it can cause agitation, it can cause, you know, perseveration. There's a lot of different different causes. Mass lesions, seizures, and others. Also medical issues, so infection, hypoxemia, metabolic arrangements, even pain. And then environmental and behavioral modifications. So, you know, making sure that patients are getting adequate rest time, that they're not having the TV on, you know, when they're when they're acting behavioral, you know, the quiet dark room. And there's also, you want to look at medications. So there's anti-convulsions. Keppra is a big one that can kind of contribute to hallucinations, as well as agitation, your psychotropics, and your narcotics, and and other medications. And so medications are great. We use a lot of medications. They help reestablish sleep-wake cycles, enhance cognitive recovery, which can increase arousal, improve attention, improve fatigue. And you can also improve side effects of injuries. So whether that's seizures, pain, agitation. But the bad thing is, is even in neurologically intact patients, medications can have side effects. They can change mood, cognition, perception, or attention. And so in neurologically impaired persons, normal doses of medications can decrease arousal, impair cognitive recovery, cause delirium, amnesia, and aggression. And so that's why, you know, there's the adage with brain injuries, start low and go slow. So a few kind of well-known ones. Haloperidol, which is a typical anti-psychotic, impairs cognitive recovery, prolongs the duration of post-traumatic amnesia, prolongs hospital length of stay. And benzodiazepines prolong post-traumatic amnesia. You know, they give them in surgery so that you have amnestic effects towards not remembering what's going on in surgery. So you can imagine in brain injury, if you're giving it to them, they're also, it's going to create that amnestic effect. Also impairs cognitive recovery. And frequently in brain-injured population, it can cause a paradoxical reaction and actually cause agitation. And so, you know, looking back at this little meme here, that's like the anti-brain injury meme that want to be worked. So I have a poll, everyone, everywhere, for people. If you want to go ahead and click on the link, we can, or go to the site, we can go ahead and ask one of the questions here. So feel free, don't feel bad about writing anything in. So what are some psychiatric side effects of medications that we use in brain injury medicine? So for example, you know, depression or agitation. I'll give you guys a minute or two to kind of type in, type in your answers. Okay, so it looks like we've got a pretty good list there. So, somnolence, anxiety, agitation, hallucinations, decreased arousal, erectile dysfunction, all very important side effects. And so, what I want to talk about in this next section is kind of the psychiatric side effects that are in commonly used medications. And so, this is just to kind of talk about how everything that we do can have an effect. So, one of the most common that we use in brain injury medicine can be imantapine, and depression can occur even at standard doses with that medication. So, that's just something to think about if you have a patient that all of a sudden presents with severe depression. Other meds that we use that commonly cause depression can be anticonvulsants, steroids, benzos, opiates, oral contraceptives, Reglan, propranolol, a lot of antihypertensives, even cimetidine. So, even something that you could use for GI prophylaxis can cause depression. And so, then we can kind of move on to mania. So, what are some medications that cause mania? So, baclofen, especially in withdrawal, you get the icky, bicky, twitchy. And so, if you're starting to see a lot of mania and someone's not taking their medication as they need to, or they've suddenly withdrawn, that can certainly be a side effect. Bromocriptine can certainly be something that can cause mania. And the interesting thing is even after the drug is withdrawn, the mania can kind of persist, as well as with captopril. And levodopa, in elderly that have been using it a long time, can cause mania as well. And antidepressants, particularly in patients with bipolar disorder, which can frequently occur with the brain injury. Hallucinations was one of the ones mentioned. That's also a good one. So, hallucinations of mantadine is more commonly in the elderly and those with poor renal function. So, you want to look at how people are clearing medication, especially if they keep coming on with some hallucinations. Anticonvulsants. So, I had a young stroke patient who was having a ton of hallucinations. So, he was on anticonvulsants after his neurosurgery, was on Keppra, and then he got started on some benzos and then was having seizures. So, he was on a lot of Seroquel. And it took a while to tease out that the hallucinations and kind of the psychosis was really due to Keppra. So, something to certainly keep in mind. Antihistamines. Higher doses, as well as the elderly, can really have side effects. Anticholinergics. Again, especially with the elderly, can certainly cause that confusion. As well as steroids. Digitalis, that they use in the cardiac world, especially in toxicity. And indomethacin. So, if you're using indomethacin in an elderly population, say for like heterotopic ossification and the patient starts having hallucinations, that's just something to think about as a potential cause. Paranoia. So, bromocriptine at any dose can cause paranoia, as well as amphetamines. So, methanidate, Adderall, they can also occur at low doses. Indomethacin, also in elderly patients. And propranolol. And aggression. So, bromocriptine also can cause aggression. Tranquilizers and hypnotics, they have that paradoxical effect. Levodopa, after a dose increase, can certainly cause some aggression. As well as carbamazepine in children and adults. Just another thing to look at. And digitalis. And then I would also, I forgot to, but I would also add levitocerin. Keppra is the brand name. So, I have another kind of poll everywhere for everyone. So, let me go to the next. So, what, I've given these kind of medications with side effects. But what are classes of medications that we're traditionally taught to use with caution in brain injury? So, for example, the ones that you want to, if you have to use them, you want to start low and go slow. So, like opiates. Antihistamines is good. All right so we've got a couple of good answers. Antihistamines, anything with some anticholinergic properties, benzos, any antipsychotics. So all good good things or not good things but good answers. And so you know benzos, GI medications which happen to be antihistamines, your neuroleptics or your antipsychotics, anticonvulsants, opiates, antiemetics, so like Reglan, some of the ones that oncology use, we want to use with caution in brain injury, as well as tricyclic antidepressants. And so benzodiazepines, they work on GABA-A receptors, they rapidly cross the blood-brain barrier, so in addition to that then you also have a disrupted blood-brain barrier and so you can kind of get a surplus of effect there. They produce an interograde amnesia and by doing that they reduce anxiety but they also decrease new learning and memory and they can produce increased confusion and agitation in brain injury patients. So if you have someone who's already thinking slowly and they're not able to kind of fully understand or think quick enough to be able to answer you and then you add on something else that's going to decrease their ability to have new learning and memory as well as impair their thinking, it can cause that paradoxical agitation and also cause significant sedation and can also cause disinhibition. Also benzodiazepines can delay motor recovery and so their use in brain injury is not recommended. If there's something else that you can try first that would be a better option. So GI medications, another thing to use with caution. So the antihistamine blockers, so cimetidine, rantididine, famotidine, all common ones used for GI prophylaxis, especially in acute care, they all have sedating potential in brain injury patients as well as in the elderly. So you know if you can switch them to a proton pump inhibitor, that would be recommended as far as for brain injury recovery. Metoclopramide, so Reglan, this would not be a recommendation, recommended medication to use. It is commonly used in like diabetics to enhance GI motility but it has significant anti-dopaminergic effects. So you know we don't use Haldol because it can impair cognitive recovery, can impair post-traumatic, can prolong post-traumatic amnesia, prolong hospital stays, and you know that works on that dopamine receptor. So kind of the same thing with Reglan. And you can also see extrapyramidal side effects with use of Reglan. So would consider trying to use erythromycin instead for any patients that are having GI motility issues with brain injury. Okay so neuroleptics or antipsychotics. So that's another group to kind of use with caution. Certainly have their role but you know the neuroleptics, they block dopamine. So in general brain injury patients tend to be dopa deficient and so you know if you're already have some low dopamine and you're taking it away you know you can kind of exacerbate the effects. So the dopaminergic antagonist is relatively contraindicated because of those lower lower levels of dopamine after the brain injury. So there's also an article that concerns that they can impair motor and cognitive recovery after TDI. So your traditional neuroleptics like Haloperidol or Haldol can impair motor recovery, can lower the seizure threshold, can cause an acknowledged seizure or worsening motor restlessness, which certainly can be interpreted by staff to be you know agitation, and can cause extrapyramidal symptoms or neuroleptic malignant syndrome. And so we know that patients with brain injury are more susceptible to medications and that they are also going to be more susceptible to the development of extrapyramidal side effects. So even with one dose of an antipsychotic, brain injury patients develop extrapyramidal side effects. So definitely something to avoid. And so I found this either in another presentation or online and I I really loved it because I feel like if there's nothing else that you can take away, it's really to try to avoid those traditional typical neuroleptics. And so you know try to save the kittens by not using Haloperidol in brain injury. So atypical antipsychotics have a lower potential for extrapyramidal effects. So their effect on cognitive outcome is not well described, but chronic use has been shown to be detrimental. There should not be considered the first line agents, but if they're refractory to other treatments or they're showing psychotic features, then you definitely want to consider it. So your atypicals are going to be Risperdal, which is an atypical antipsychotic that acts at the D2 as well as the serotonin receptor. Your olanzapine or Zyprexa is also a good one. It tends to be a little more sedating. So an advantage of olanzapine is it tends to have less cardiac side effects, so less effect on IQTC. Abilify case reports support the use in it as well. It tends to be sedating in a younger population, but activating in an older population as well. And then Keatopine or Seroquel. So this is one of the medications that's least likely to produce extrapyramidal side effects in vulnerable patients. And so it has a lower incidence than Risperdal. Risperdal is really good if there's kind of psychotic features and Keatopine is a lot better kind of for the behavioral features. And so in a study of Keatopine, there were seven TBI subjects that were at least three months after injury. They monitored the overt aggression scale and found that there was nearly an 85% reduction in the global impression of agitation and reduction. So there was sedation reported in three and those patients were taking anywhere from 25 to 300 milligrams a day for six months. Ziprosedone or Giodon. They did a case series of five severe head injury patients with post-traumatic amnesia and agitation. The agitated behavior scale, which is one of the combi scales, decreased with 40 to 80 milligrams a day for two weeks. Treatment ranged from about 5 to 10 weeks. And the good thing is that there was no side effects noted. So kind of this next question here is just looking at what is going to be, what is one thing that you need to think about when you're starting someone on a couple of these medications. So if you want to go ahead and answer the question of what's something that you need to check when you're starting these medications. Okay, so I have a pretty smart crew here. So yeah, you want to make sure that you're checking the QTC when you're working with those medications because it can prolong it. Zyprexa is one that tends to have a little bit of a lesser effect, but certainly with Gedon or Ziprasidone and Querapine, you certainly want to, especially as you're making dose adjustments or initiating, be monitoring the QTC. So another group of medications that you kind of want to use with caution is the anticonvulsants. And so the practice parameters from the American Academy of Neurology, of Neurosurgery, and ACAMNR all recommend that anticonvulsant prophylaxis after traumatic brain injury is warranted for only one week after a closed head injury. And so you also want to use them with caution as they may have cognitive side effects. For example, the long-term use of phenytoin has been showed to have adverse cognitive side effects and even more so than Tegretol. The deleterious effect of phenobarb on cognition has also been well described and kind of anecdotal evidence. I told you earlier about Levotiracetam or Keppra, has also been known to cause agitation. Also another thing to look at is hyponatremia. And it can happen pretty rapidly. So if you have a big change in behavior, confusion, look at hyponatremia and look at what drugs may be causing it. Antidepressants as well as anticonvulsants can all have profound effect on sodium levels. So carbamazepine or Tegretol can cause hyponatremia, SIADH, as well as dizziness. And same with Depakote or valproic acid. You know, use it a lot to help manage behavior, but if it's dropping your sodium and the behavior is not getting better, that can also be a cause, as well as the SIADH and dizziness. Opiates want to use the lowest possible doses because they can produce sedation, can produce hallucinations, especially in elderly population, and decreased attention in the TBI patient. So also would want to use short-acting agents rather than the longer-acting to initiate and consider the use of the agonist-antagonist. And you know, of course, the adage, start low and go slow. Antiemetics. So Reglan or metoclopramide is a good example of one of the dopamine antagonists that's also used as an antiemetic. Domperadone and chlorpromazine also have those effects and they really act kind of similar to the antipsychotics. Promethazine or Phenergan is another example. It's an antiemetic, but it's a first-generation antihistamines. So antihistamines, we list it as one of the medications to use with caution. And odandacetron or Zofran, it selectively antagonizes seroponin receptors. So if you're trying to supplement seroponin and you have something else that's taken away, you know, something to think about and use with caution. So antidepressants, want to avoid those with anticholinergic activities. So tricyclics can certainly have that, as well as lower the seizure threshold. So SSRIs are the drugs of choice for the treatment of depression in the TBI patient. Trazodone has also been used and recommended, and SNRIs show promise. So norepinephrine is one of those that works on initiation. So trying the venlafaxine or the duloxetine might also have some propagation for improving initiation. And so now, kind of move on to medications that can be used to enhance cognition and recovery. And so you have your dopamine agonists. So amantadine, kind of in that well-known study from the New England Journal. Methylphenidate, also a big study that showed a favorable outcome. And dextroamphetamine are all dopamine agonists that can be used to help with cognitive recovery. You also have the norepinephrine agonists. So methylphenidate, dextroamphetamine, and atomoxidine, or strotera, as well as your NMDA receptor antagonist, or amantadine. All those are considered to be stimulants and cognitive enhancers, and so we use those really frequently. Selective serotonin reuptake inhibitors, so your SSRIs. Sertraline and Zoloft has the most serotonergic activity, also tends to be a little more activating. Citalopram or Celexa is one of the most studied, tends to also help a lot with anxiety. S-citalopram or Lexapro has kind of the quickest onset, so I personally like to use that a lot more frequently. And fluoxetine or Prozac, that's also had the flame trial that showed the link with post-stroke motor recovery and that improvement. So that's also a big study that came out. One thing to to kind of keep in mind is this these SSRIs can also cause hyponatremia, so want to be careful when you use those. So the flame trial was a study done in 2011 that had 118 patients that were randomly assigned to fluoxetine or placebo, and what they found is patients with ischemic stroke and moderate to severe motor recovery deficit, the earlier onset of the prescription with fluoxetine and therapy enhanced motor recovery after three months. And so it was, you know, theorized that the modulation of spontaneous brain plasticity is there to help as well with motor recovery. SSRIs and TBI, and the most kind of well-studied, you know, is Celexa and Sertraline. And so they recommend the use of Sertraline as a first-line option for the treatment of post-TBI depression. Among the SSRIs, it has the most dopaminergic and serotonergic effects, so definitely a good one to be using. And your serotonin norepinephrine inhibitors, so that's norepinephrine theoretically involved in initiation, can also help with pain control. So it's been shown, you know, shows promise for individuals with brain injury, and that's your Venlapaxine or Effexor and your Duloxetine or Cymbalta. And you also have your cholinergics. So Dinepazil or Aricept is kind of the one that's the most studied. They've been, you know, it's used for memory in patients with dementia, but they also found that, you know, it improves short-term memory in the brain-injured populations. And so the effects even lasted after the washout periods where the medication was stopped. It's been shown to improve intention and improvement in aphasia. Tends to work better in broken aphasias, you know, that have vascular insult to the cholinergic pathway. Okay, and agitation. So agitation after TBI. Adults are three times more likely in the first six months after head injury to show aggression than those with just multiple traumatic injuries without a head injury. Makes sense. So 25% of adults showed aggressive behavior 60 months after discharge from inpatient rehabilitation unit for TBI. So, you know, that's one in four. That's a significant population. So if you have, if you're gonna have an outpatient clinic, it's gonna probably be something that you're gonna run across. 70% of adults during inpatient TBI experience agitation. And it's been shown to negatively affect the rate of recovery in acute inpatient rehabilitation. And you can imagine by just because of the number of treatments that you probably need to implement or, you know, the confusion that kind of persists with patients that, you know, have required treatment. And so an important thing to recognize is that, you know, you have agitation, but it is part of the TBI recovery process. So when you look at the ranchal levels, ranchal four is confused and agitated. So the patient's confused, they're restless, and that, you know, that's not necessarily a bad thing. They just need to kind of help, we need to help kind of facilitate them through that on to that next level. And so symptoms would be physical and verbal aggression. You know, there's all kinds of different types of agitation, explosive anger, akesthesia, that inner restlessness that can sometimes be labeled as agitation, irritability, kind of lability and mood, maladaptive behavior, a lot of them, a lot of people that get TBIs can kind of have maladaptive behaviors premorbidly, as well as disorientation. You know, you wake up in the middle of the night, you don't know where you are, and you don't know what's going on because you've had a brain injury, and people are trying to tell you to do all this stuff. It, you know, it can be pretty confusing and disconcerting. So non-pharmacologic management of post-TBI agitation, so quiet, dark room, so reduce noise, turn off TV or monitors if possible, reduce the number of visitors and interruptions, try to cluster vitals and med administration for nursing care, and, you know, allow downtime for the patients. A lot of times they'll get really tired and they can't tell you that they're tired, so they'll start to get really restless, and sometimes they just need a break and just to chill out for a little bit. And then you want to reduce the contributors to education, so try orientation and memory strategies. If they're not sure what's going on or what's, you know, what day it is, all that stuff, try to put things that are going to be there to help orient them and to help that they can recognize things that would be familiar. Also want to look at pain as being a thing that can contribute to a lot of agitation, especially someone that, you know, is brain injured, they're not mixing, making the connection that, hey, I'm having my pain, I need to ask for something for that. And then a big one is to eliminate unnecessary medications, kind of the medications that we talked about to use with caution. And behavioral management. Here we use, for behavioral patients, we use behavioral plans, and a lot of times that's more to help address the staff and family and everything and how to interact with brain injury patients, but also then to remind the brain injury patient, you know, things that we're looking for and goals that they have. And it's important to incorporate the entire care team, so family members, psychology, nursing, therapists. All right, so we have another poll. Okay, so we talked a little bit about this, but what are examples of things that can contribute to agitation? So infection would be another great one. Okay, so lots of good answers there and you know it is definitely all those things will have the ability to contribute to post TBI agitation and so sleep disruption saw that a few times, alterations in sleep-wake cycle lines, discomfort, rectal tubes, NDs and unidentified injuries such as fractures that can also all cause pain, sources of discomfort, inadequate pain control, constipation I saw that on there, ileus, even GERD, seizures, subclinical seizures can also manifest as agitation, disorientation, kind of confusion being in post-traumatic amnesia, neuroendocrine dysfunctions, so hypopituitarism, thyroid issues, as well as hydrocephalus, always a couple of things medically to kind of keep in the back of your mind, that's all, all potential causes. And so preferred medications for post-traumatic agitation, so there's kind of two schools of thought, one of the schools of thought is that you know they're, so one of the schools of thought is that they're overstimulated and so you want to decrease that stimulation and so then you want to kind of slow them down. The other school of thought is you know that they're confused because they're not thinking fast enough and so if you speed them up and it'll help with agitation. And so some preferred medications include neurostimulants, so such as the ones we used before, or mentioned before, such as methenidate, amantadine, denepazole, then to kind of slow them down or decrease agitation you can try with the beta blockers, propranolol is kind of the most studied. Your SSRIs, so helping with that anxiety, that was one of the the comments that you guys said, which is a great one. And as well as mood stabilizers, that's another option that you can use, like falproic acid to kind of help treat that and level it out. Then you also have your atypical antipsychotics, that's going to be your geodon or your zibracidone, keatopine, risperidone. And then another one that's starting to get more used is Nudexta, which is a brand name for medication, it's a combination pill. And so it's also used, they're doing a study I think in Alzheimer's patients with agitation with regard to it, but it's used for pseudovolvular affect after stroke, or is what it's FDA approved for. So the post-traumatic agitation, so you really kind of look at what are you, what's the, what are you seeing that you want to treat? Is the agitation because of decreased arousal or attention? Then you want to use the neurostimulants. Is it that akesthesia or that inner restlessness? Then you want to try something like imantadine. Is it anger or directed aggressions? A lot of times it can be directed towards like a family member, that's when you would want to try more things that are like a mood stabilizer, such as valproic acid. Poor sleep, trazodone is a really good option for that. Anxiety, you can do your SSRIs. So, you know, citalopram is a good one for anxiety. Same with escitalopram. And then the agitation that has kind of psychotic features, that's when you want to kind of consider more of those atypical antipsychotics, such as risperidone or ketopine. Okay, and so this is a picture of my, my cat, Ellie. And if you look at it, she looks really agitated. And so I wish this, I could have uploaded this as a live photo, because she was actually mid-neon. So this is just an example to think of what looks like aggression might actually be poor sleep or tired. So yeah, she was, she was mid-neon, and I just happened to catch the perfect photo. So I always love that one. The agitated behavior scale is a scale that you can use. It's scored from 1 to 4, and it's based on a bunch of different behaviors. And so a score that's greater than or equal to 21 is fine to be agitated. And it's been shown to have really good inter and intra radar reliability. So we talked a little bit about the non-pharmacologic treatments for agitation. So now we can talk about the pharmacologic treatments. And so you have your stimulants. And so amantadine was found to be the preferred agent for agitation in patients with TBI. That was back in the 90s. I'd also say that methylphenidate or the other dopamine agonists are also preferred agents. And the methylphenidate TBI related anger of 38 persons was significantly reduced in that group. And so also have your mood stabilizers, your SSRIs, beta blockers, that propranolol, and the atypicals, kind of if all else fails. And so we talked a little bit about the dextromethorphan, quinidine, or Nudexta. It's proved for pseudobulbar affect, but it's demonstrated clinical efficacy and was well tolerated in the treatment of Alzheimer's type agitation. It's another one that you want to definitely monitor the QTC with. Okay. And so some kind of clinical tips. So again, start low and go slow. Try to recognize what's causing the behavior. Is it pain? Is it fatigue? Is it frustration? Attempt to avoid medications with sedative and cognitive side effects, such as benzos, prolonged PTA, anticholinergics can cause confusion. And that typical neuroleptics can impede cognitive recovery. And remember to save the kittens. But most importantly, sleep is very, very important. And here's my references that will be available. Okay, any questions or any? Yeah, thank you so much. I'm just reading through a couple of questions here. One is, well, I think this is complicated. This kind of goes into things that you were talking about at various points through your talk. One of them is, what is the drug of choice to treat an acute agitation or aggression post-TBI? And are there any, you know, addenda to this with regard to pediatric population? So I'm not, I'm not peed. So I haven't, I haven't seen peed since, since my training. So I can't really speak a ton to that. Sorry, I was trying to see if I was still muted. But there we go. Okay. So I would say for acute agitation, that you need to treat acutely. So the IM injections, either Ziprasidone or Geodon or Zyprexa would probably be kind of first line agents for that kind of acute. All right. And when do you use beta blockers as first line in agitation? I think, you know, it's going to take a little while for an oral medication to take effect. So, you know, you would, you'd want to use it if, if you have someone that's kind of that inner restlessness or that, you know, anxiety, they can kind of help slow down. They can kind of slow you down a little bit. They can cause some drowsiness. So that's something to be kind of be aware of. Okay. That's great. Thank you so much. It looks like, hold on just a second. We're getting one more. Oh, that's a good point. So this is something I think that comes up. The start low, go slow approach can be tough in the TBI unit because people, you know, staff are getting frustrated, family members can be frustrated within the first few days of admission. So if SSRIs take, you know, two to six weeks So, so if I have a patient that's a brain injury patient that comes onto the floor, it's usually, usually you have a washout of trying to get them off medications that are less desirable and getting them on something like stimulants. So usually it can be kind of a rough couple of weeks before you can get them on the floor. So if I have a patient that's a brain injury patient something like stimulants. So usually it can be kind of a rough couple of days as you're washing that out. I personally like to use escitalofram because it has a quicker onset at about the two weeks. So, you know, especially something like that can certainly take, take a while. But, you know, especially if you're supplementing kind of with a stimulants and getting them good sleep, good sleep is so important. Making sure that they're getting sleep at night. Usually, you know, you can have a couple of days where things start getting better. Okay. Do you use provigil at all as a stimulant? Yes. Yep. Especially where amantadine can be kind of relatively contraindicated. So if someone has kind of renal problems or they're on dialysis, then we'll consider provigil or if they're older. Okay. And this kind of goes back to the FLAME trial. How long do you recommend using fluoxetine in inpatient stroke or TBI? I'll usually use it throughout the length of their stay and kind of continue them on it. Okay. Yeah. Okay, great. Thank you very much. I appreciate this. This has been really helpful. I think we're out of questions. If anybody has any more questions, we have your Twitter information here. Yeah. I think, let me see if it popped back up there. But yeah, if you have any questions, feel free to shoot me an email or message me on Twitter. All right.

neuropharmacology

rehabilitation

traumatic brain injury

brain injury effects

neurobehavioral symptoms

medications for TBI

non-pharmacological management

post-TBI agitation

importance of sleep in TBI recovery