And we would like to give a big thank you to Avenir. This activity has been supported in BART by them. So having said that, I'm going to stop sharing and turn this over to Dr. Zorowitz. Thank you very much and welcome to the webinar. We're going to start with a brief talk about mood disorders in brain injury introduction and epidemiology. So the objectives of this are basically to describe the common mood disturbances observed in brain injury populations, list criteria specifically for major depression disorder, anxieties, post-traumatic stress, and pseudobulbar affect, and then finally to discuss the epidemiology of these common mood disturbances experienced by patients with brain injury. Just as disclosures, I have nothing to disclose from this. I have done previous work with Avenir, all of which has now been published. Anyway, so to start off, basically while there's a lot of things that happen after TBI, really neuropsychiatric complications really are of the most common. And so part of getting through TBI really means that we have to diagnose and intervene that will address these things. And so the problem is that, as you're aware, unrecognized untreated neuropsychiatric problems after TBI actually can hinder participation in all of our interventions and really hinder optimal recovery. It also significantly impacts relationships which support networks are predicated. So essentially, it also may have problems with safety issues and things such as violence, self-directed violence, especially suicide and things like that. So it's really important that we have to identify and look at these things. So what we're going to look at really are mood disorders. And just to give you an idea, mood disorders as opposed to disorders of affect sort of go along the same way as say the weather and the climate does. So weather is sort of what happens during the day, but the climate may be a temperate climate, may be tropical and all that. So it's just sort of the underlying temperature and stuff. And so that's kind of the same thing here. Mood disorders really involve some sort of a pervasive and sustained alteration in someone's status. And that may last over days, weeks, or months, whereas affect really is the discrete and brief episodes of abnormal emotions and alterations that may last very, very short times. So having said that, let's go into the mood disorders and start going through some of the criteria. So the first thing is mood disorders. So essentially, when you're talking about mood disorders and specifically depression, it really is characterized by a diminished interest and pleasure in activities that have to last most of the day or nearly every day for at least two weeks. And here are all the things that we normally look at. It can involve feelings of hopelessness, worthlessness, concentration problems, suicidal ideations, and then the physical things that happen, weight loss or gain, problems with sleep, either psychomotor agitation or retardation or fatigue or low energy. So all these things are things that we have to look for in looking at these things. And again, what we try to do is really look at this based upon observation and interview. But then there are other things that we can look at to help diagnose these things. So self-reporting scales, such as the BEC, the PHQ-9, I'm sure everybody is familiar with, starting with the PHQ-2, and also the neurobehavioral functioning inventory depression scale are things that are self-reporting for patients to look at. And then there are, of course, clinician-rated scales, such as the Hamilton and the CESD, are important to look at too. But given the high rate of problems also that can happen organically, such as neuroendocrine abnormalities, you also have to look at things like thyroid dysfunction as well as other things while you're looking for mood disorders as well. So what's the epidemiology? Depending on the study, it's very, very varied. So as you can tell, it probably goes under diagnosed and under treated. Frequency during the first year, as you can see, is also very varied. And lifetime prevalence is also quite varied depending on the studies. They are more frequent among patients with TBI than people with severe orthopedic injuries. Mood disorders can coexist with other things like anxiety. And then you also have to remember that things like substance misuse may be comorbid with depression and is a big risk factor, not only for TBI itself, but for subsequent development of mood disorders as well. And then the last thing we want to talk about with mood disorders really is the differential diagnosis. And again, a lot of different things can mimic these, so you have to be on the lookout for them. So mood disturbances associated with delirium, substance-related mood disorders, adjustment disorders, pathologic laughing and crying, which we'll be talking about, post-traumatic irritability, affective lability, PTSD, as well as some of these other things. So let's go on then to anxiety. So anxiety really is defined as an anticipation of future threat. It can happen either discreetly through things like panic attacks or maybe more diffusely through things like generalized anxiety. Or it can be a combination of these things, which can basically refer to fear or avoidance of places and situations, on top of which then you have some of those panic things that may cause you to feel trapped or helpless or embarrassed. When you have this, you're looking for excessive anxiety or worry for more days, for not at least six months, about a number of things. Basically, they're difficult to control, and they are associated with either three or more of these things, either restlessness, being fatigued, difficulty with concentration, irritability, muscle tension, or sleep disturbances. They, of course, cause a lot of distress, but they're not attributable to other things like substance abuse or other medical conditions, and they are not better explained by other medical disorders, of which there is a huge list of here, which I'm not going to go through. If you look at generalized anxiety disorders, excessive worry is characterized with this. About, again, a number of events or activities that occur more days than not for at least six months, and again, the similar kinds of things that we talked about before, and they have to have at least three of those things happening. Diagnosis, again, a lot of these things get diagnosed by clinical interview. Then basically, you can look at the DSM-5 criteria as we've gone through, as well as some of the scales that are out there, such as the GAD-7, which is a self-report of the panic disorder severity scale, which is also a self-report. Then just remember with anxiety that you can also have depression, PTSD, and other things along those lines like headaches, dizziness, paresthesias may be difficult to differentiate. It can also have problems in association with pain, medication side effects, and substance abuse as well. Again, you have to go through and really tease all these things out. Epidemiology, new onset after TBI, again, can be very varied depending on the studies that you look at. The most common post-traumatic anxiety disorder that gets diagnosed is what's called anxiety disorder, not otherwise specified. It usually occurs after the first year and has subthreshold symptoms, which can be combined with PTSD or generalized anxiety disorder. Moving on to post-traumatic stress, again, these are symptoms that last more than one month with significant symptom-related distress or functional impairment. They have to have these four categories, and I didn't go through all the different aspects of these, but you can look those up. Those include intrusion, avoidance of trauma reminders, any negative alterations in cognition or mood, such as dysphoria, or anything hyperarousable, heightened startle responses, sleep disturbances, and going through those things. Again, diagnosis is done by clinical interview as well as some of the scales, such as the CAHPS-5, the PCL-5, the TSI-2, and the DAPS, all of which can be used, as you can see here. Some of them have good benchmarks to work from. These are some of the things that you can do. Epidemiology, PTSD occurs more frequently in TBI than non-TBI patients. As you can see here, patients with mild TBI and orthopedic patients and with non-brain injury are more likely to report PTSD and depressive symptoms six months after intergery. The interesting thing about it is, of course, people who don't have the cognitive deficits associated with TBI tend to report PTSD more than patients who have moderate to severe TBI. Then finally, recent meta-analysis shows that PTSD is related to a shorter period of post-traumatic amnesia. Again, if you're not remembering things, chances are you're not going to have PTSD or at least not report it. Differential diagnosis, again, can be all of these things. Adjustment disorders, panic or generalized anxiety disorders go along with this, OCD, major depression, as well as some of the other personality disorders that may closely resemble these things. Then finally, pseudobulbar affect. There are a couple different people who have looked at these things. Basically, the idea is that emotional responses are situationally inappropriate, so either laughing or crying. The feelings and affective responses are not closely related. Duration and severity can't be controlled by the patient. An expression of the emotion doesn't lead to a feeling of relief. Essentially, these are inappropriate laughing and crying episodes that are not consistent with what's going on around the patient, but they do cause distress. They're not accounted for by other things and not usually due to drugs. Diagnosis, the major way to diagnose PBA is with the CNS-LS, which is a seven-item self-administered questionnaire that talks about the control of laughter and crying. It's been validated in ALS and MS, but not in stroke and TBI. You can have any scores really from five to 35. A cutoff of 13 usually predicts the presence of PBA. Another scale is the pathologic laughter and crying scale, which is 18 questions. It's been validated in patients with acute stroke. It has good interrater and test-retest reliability. Again, a cutoff score of 13 in here may predict the presence of PBA. Just to give you an idea, you can see in a number of studies, there's a lot of variability in the numbers of patients that have PBA. We looked at these, although this is not here. The PRISM-2 study is the study that I participated in that looked in stroke and TBI. Then finally, differential diagnosis. You just need to remember that it can look very, very much like depression. It can look like essential crying, which is a lifelong lower threshold for weeping. It may look like a thing called witzelschucht, which is the patient appropriately finds situations funny that others don't and are just basically insensitive to humor. Then essentially, they may go along with post-traumatic stress and possibly with anxiety. Finally, just to know that patients with PBA have a higher prevalence of anxiety, not surprisingly. They may also have a higher prevalence of diagnosable psychiatric disorders. 30 to 35 percent are depressed. These things certainly interfere with rehabilitation. In locked-in syndrome, PBA may have interfered with things like swallowing dysfunction and effective use of remaining motor ability and communication abilities as well. These are all things that we need to keep in mind when we look at PBA. Since I know I am pretty much out of time, just to show you PBA versus depression, there are differences in those. Hopefully, we'll be able to look at those. The same thing between pseudovulvar affect and post-traumatic stress disorder, there are some differences to look at as well. I'm going to stop there. Who am I turning it over to? I think, am I going to Christine? Okay. We'll go on. Thank you, Dr. Zor. Thank you for watching! Thank you everybody. My name is Christine Grace and I am here to just kind of tag on to everything that Dr. Zorowicz had mentioned. So mainly the issue with neurobehavioral and neuropsychiatric disturbances following brain injury is a dysregulation or disruption in neurotransmitter pathways. And so as you see with improvement in neurorecovery and resultant decrease in neurodepressive symptoms, it's important to create a balance between the neuroexcitatory neurotransmitters, which we see on the right, and then the neuroinhibitory or the main neuroinhibitory, the major brake system of the brain on the left. And so the way the brain was designed is really more like three or four major gas pedals, but then one major brake system. And the brake pedal actually happens to be a lot larger and stronger than all of the neuroexcitatory pathways combined. And it's very important to understand that concept. So starting with dopamine, originates obviously in the midbrains of Sancho Nigra, has pathways that are named basically from its origin to the end result. So mesocortical would originate in the mesencephalon and end in the cerebral cortex or higher level cortices and is responsible for cognition arousal. Mesolimbic system, again, starting in the mesencephalon, ending in the limbic system, responsible for emotion, behavior, delusion, and hallucination. The nigrostriatal pathways are responsible for movement and coordination. And the tuber infundibular is responsible for the prolactin secretion. In terms for serotonin, we see here that a major known fact of serotonin is that it's actually made in the gut. 90% of serotonin is made chromatograph in cells, as opposed to common you know, thought that it's made in the brain. Only 10% or so is made in the rathionucleus in the brain. And this is actually why we call the gut our first brain. Terms, even in olden times, term gut feeling, butterflies in my stomach, really come from this concept. Serotonin receptors are too numerous to list. And as you can see with the pathways, they're not named the same way as the dopaminergic pathways. Serotonergic pathways are mainly where they end. And so there is a correlation and an aggregation of serotonergic pathways in the frontal cortex. They are more responsible for mood. If this aggregate of serotonin pathways ends at the basal ganglia, they're more responsible for movement and obsession and compulsions. In the limbic area, those areas are responsible for anxiety and panic. And any aggregates of serotonin receptors in the hypothalamus responsible for appetite. And last but not least in the brainstem, it modulates sleep, especially slow wave sleep. Neuroepinephrine, or also known as common term adrenaline, originates in the leucocereus. The receptors are mainly in alpha and beta. Neuroepinephrine pathways, interestingly enough, do not develop until later in life, anywhere between ages 18 to about 25. Responsible for decision making, attention, judgment calls, but also responsible for emotional regulation. When it comes to any posterior or midbrain hindbrain pathway, it also is responsible for cerebellum and blood pressure. It's mainly the autonomic functional controls. Acetylcholine is another major neurotransmitter, major chemical player in the brain. It's made in the nucleus bacillus of minor in the forebrain. And this is also the reason why our ability to maintain higher order cognitive processes, short-term memory, not just long-term memory, and the ability to lay down new memory really stems later on as we develop our forebrain. Receptors are nicotinic and muscarinic. Pathways involve mainly the forebrain, the midbrain, the brainstem, but there are little pathways of acetylcholine in the cerebellum. And that being said, it's really important to remember that as these pathways were developing, they didn't make their way towards the cerebellum because as we were developing as humans, we took several falls while learning how to walk and maintain balance. And it's not really pleasant for the brain to remember those falls. And as a result, it's important not to register some of those poor memories, a failure of cerebellar and acetylcholine activity. And so it was really made by, in a nice design, but it's really responsible for short-term memory, new learning. It projects along the diagonal band, the prefrontal cortex, and the thalamus. So the main brake system of the brain is gabaminobutyric acid. It's the most widespread neurotransmitter. It inhibits dopamine, acetylcholine, norepinephrine, and it modulates excitotoxicity of glutamate. It's very neuroprotective, as we all know, in the first few hours or days following a brain injury. And it reduces metabolic demands. And it's believed to also reduce the rate of recovery following TBI if it is prolonged, or if these GABAergic pathways are activated due to any secondary pharmacologic interventions that may take place following a brain injury. And so, as Dr. Swarwitz had mentioned, with depression, these are some of the main criteria that we look at when it comes to depression. And we always want to tie this to serotonergic and dopaminergic pathways, which is also the main reason why the approach in managing depression happens to also be approaching these two neurotransmitters. So when we look at mechanism of action of specific drugs, we really want them to coincide and alter and modulate these pathways. When it comes to anxiety, again, as Dr. Swarwitz had mentioned, it's really an anxiety or an excessive worry that's at least six months, and it's experienced, and it's very challenging to control. And then three of the following criteria, and it's important to also note with children, some of these symptoms, they only really need one out of these criteria for a diagnosis of generalized anxiety disorder. With anxiety, we think more so serotonin, but also poor GABA regulation. And it's really an alteration in the GABAergic pathways, and some may say also a reduction in the GABAergic pathways. As a result, this is when patients who suffer from anxiety tend to reach more for the GABAergic substances, whether it's pharmacologic substances or, you know, commonly abused substances such as alcohol. Now, as we can see here, GABA modulates the release of dopamine as well as glutamine, and serves as that inhibitory action. With that poor regulation, you get almost uninhibited glutaminergic glutamate activity. As we can see, comparison between major depression and anxiety with major depression, as you see the symptoms on the left, anxiety is more so the restlessness, and they're more on overdrive than anything else. And that is the major prevalence of the clinical presentation. PTSD is slightly different. PTSD, there must be an actual event, whether it's a threat to death, I'm sorry, a threat to life, whether it's serious injury or sexual violence, and it must affect the patient in one of the following ways, and it could be more than one of the following ways. Mainly, if it's a direct experience, if they witness the experience, if the experience occurred to a close family or friend, and if it was repeated or extreme exposure, then they generally suffer from one or more of the following symptoms. Some either they have recurrent or voluntary symptoms. Some patients do have distressed dreams. In children, they may actually either act out these dreams, or they may feel the need to stay in a form of play. Others complain of dissociative reactions. Some experience intense psychological distress internally, and others also avoid specific stimulus. And then here, we have listed a few other presentations and just examples of what they avoid in terms of traumatic events. They also have to have two or more of altered cognition or altered mood that's associated with the traumatic event. It's important to note that they are in a persistent negative emotional state and detach themselves, and they have negative beliefs, and it must not be due to other factors such as head injury, alcohol, or drugs. If they're just generalized PTSD, because we see in PTSD related to head injury, they may not have any of these criteria. In PTSD, this disturbance does last quite a significant amount of time, and it does cause a lot of social impairment. So when we compare major depressive disorder compared to PTSD, we see that there is common ground when it comes to substance abuse, suicidal ideation, negative thoughts. They do also present with some anxiety features other than their significant distress and social impairment. With pseudobulbar affect, it's a little bit different of a presentation. As opposed to it being a psychiatric disorder, pseudobulbar affect is actually a neurological disorder. It is characterized by a dysregulation of expression or affect, not feelings or mood. It is involuntary, sudden, and frequent, and it is exaggerated or really not compatible with the patient's underlying mood. There is a deficit in the NMDA receptor, which modulates glutamate activity and the corticopontine cerebellar circuit. So we can see here that the circuitry or this network between the cerebral cortex, the PON, and the cerebellum are disrupted. And so as we can see with the comparison, and also mentioned by Dr. Zorowitz, the duration is very short with PBA. There is really no control whatsoever. This is a neurological condition. It is unrelated to or independent of mood. It doesn't change. There's no misperceptions. It's usually there is no impairment of insight, and there is no stimulus, or the stimulus may be even inappropriate to the situation. So these are three common theories or hypotheses about damage in brain pathways in pseudobulbar affect. There's the disconnect hypothesis, which tells us that corticobulbar traps may release bulbar-generated laughing or crying from cortical control. The cerebellar hypothesis just goes over what we mentioned, the corticopontine cerebellar disconnect, and then the monamine hypothesis also with disruptions in those centers. So as we can see here, as mentioned prior, these are some of the diagnosis in which PBA was studied. And in an online survey, they were found that it was important to recognize PBA symptoms since they were easily confused with neurodepressive symptoms. The duration is key in terms of PBA lasting seconds to minutes, but episodes of depression lasting weeks to months. And when it came to crying in depression versus crying in pseudobulbar affect, in depression, their affect matches the mood, but in PBA, there is no congruency. In treatment, and since we were discussing it, it was important to know that dextromethorphan is thought to regulate glutamate signaling. The combination of dextromethorphan and quinidine was one of the factors in terms of the dextromethorphan modulating NMDA activity, and quinidine being a CYP450, as well as reducing breakdown of the dextromethorphan so that it can last longer, and it modulates NMDA response to the glutamate. Thank you very much. So I'll hand this over to Dr. Fusco. So thank you for the wonderful presentation. So I'm going to pull up my slides. All right. I'm going to take over the baton and actually talk about the pharmacological and therapeutic interventions for depression, anxiety, and PTSD to complete the discussion. I know Christine just talked about pseudobulbar affect. My name is Dr. Fusco. I work at NYU and in the field of brain injury. So what we're going to talk about is we're going to kind of first understand the recovery trajectory after traumatic brain injury and how it guides the treatment for the neurobehavioral disturbances. It's important. We'll get into why that's important. We're going to review pharmacological management of neurobehavioral disturbances and focus on anxiety, depression, and PTSD. Obviously, there's a lot more neurobehavioral disturbances after traumatic brain injury, but we're going to focus on these three in this part and then we will review the non-pharmacological therapeutic interventions. So the first we kind of have to get into is kind of understanding traumatic brain injury. There's generally a predictable trajectory. You have your post-traumatic coma, your post-traumatic confusional state, post-traumatic amnesia, post-traumatic dis-executive syndrome, and we'll talk about how it's important to understand each stage and why that can affect your treatment for mood disorders. In the post-traumatic confusional state, and I kind of skip post-traumatic coma or your disorders of consciousness phase because you're not going to necessarily see those in those phases. So in post-traumatic confusional state, they're kind of in a post-traumatic delirium. The patient's awake, conscious, but has fluctuating impairments of attention, memory, and orientation. They often present as confused, agitated, or aggressive. They can communicate with variable accuracy and social appropriateness. You know, these are your patients in acute rehab on a one-to-one, giving, you know, the ones that the nurses and now the staff are very occupied with. They may also, you know, the patients also may have disturbed sleep-wake cycle perceptual disturbances, which may look like illusions or hallucinations or just, you know, general confusion. Sometimes these can be seen with a vision disorder or, you know, a lobectomy, you know, where they're kind of filling in the blanks, delusions, confabulations, and emotional ability. In post-traumatic amnesia, you know, so this is the next state. So we know the key, oops, the key feature is actually impaired new learning or anterior grade amnesia. So they're not, they may know things from before, but they're not making new memories. So they're, it's due to the fact that the brain is injured and it has an inability to consolidate new information, orientation information, autobiographical data for peri and post-injury period. How did you get to the hospital? What hospital are you in? How long have you been here? You know, they're just not able to organize that in their head and hold onto it and make a response. They may have fluctuations. They may fluctuate. They may have fluctuating agitation and aggression and basic attention, you know, as compared to the post-traumatic confusional state. They may have impairments of higher level attention. It's, you know, they're not going to be able to kind of hold onto things or attend to, you know, multiple people in the room, multiple tasks, impairments in working memory, executive function insight. So they're not going to remember, oh, I can't get up and walk around because my left leg is weak and I would fall. And I fell, I fell yesterday. I'm frustrated by this. And, you know, as we know, and it's on every board question, brain injury boards, undergraduate boards, any board, they love to say time from the injury to emergence from PTA is important for prognosis. If you can come out of post-traumatic amnesia on the GOAT or the OLOG within 30 days, you're usually doing really well. If it's longer than two months, you're going to have more problems, you know, for life. Post-traumatic dis-executive syndrome. Uh, this, the key feature is executive dysfunction. These are our outpatients. They haven't improved new learning as compared to post-traumatic amnesia. They're going to be independent for basic ADLs. They can get up, brush their teeth, get up, get into the shower, but you know, more complex tasks. They may need some help. Maybe they can make a peanut butter sandwich, but you wouldn't want them, you know, making Thanksgiving dinner, purposeful, socially appropriate behavior. There's higher level cognitive impairments such as complex attention, you know, driving, uh, taking the train with multiple connections, working memory, declarative memory retrieval, not new learning and problems in motor planning. So they're, they're going to need supervision for community living. So, you know, maybe they know to take the train to go somewhere, but, um, what happens if the train is not working and they have to, you know, take a detour that's going to be problematic. So it's important to kind of evaluate and manage, uh, neurobehavioral disorders after TBI. You really, in order to do this, you need to know where you are in their trajectory. Are you in post-traumatic delirium, post-traumatic amnesia, or post-executive, uh, dis-executive, uh, post-traumatic dis-executive syndrome. You want to know what, you know, neurobehavioral domains you're dealing with. What are you, what's the presentation? Are they anxious? Are they psychotic? Do they have an affect disorder? Because it's going to change, you know, not the treatments for psychosis are not the same as the treatments for depression. You want to under, uh, and obviously the treatment for pseudobulbar affect is very different than the treatment for depression. Address underlying contributors, which will breeze through, um, use non-pharmacological strategies where possible, and, you know, you can do tar- targeted pharmacotherapy. Um, so why do you want to know where you are in the trajectory? Well, it really kind of provides a framework for understanding the neurobehavioral disturbance. If they're in post-traumatic amnesia versus post-traumatic executive dis-, you know, dysfunction, your approach is going to be a lot different. Um, you can still include a psychologist and a neuropsychologist, but their approach is going to be greatly different. And as they navigate through that trajectory, your treatment that worked is going to change what they needed on the, uh, in PTA is not going to be the same that they need six months later. So it's important to follow these patients. Um, again, anticipate treatment adjustments. Identify deviations from the trajectory. So patients are expected to recover. They can plateau, but they shouldn't regress. So somebody who's in PTA, you know, agitated, who, you know, eventually breezes through should not go back to being confused and having no memory. Something is going on. Um, you know, you want to investigate neurological medical or neuropsychiatric disorders, emergence from something, um, hydrocephalus, UTI. We see it all the time. Something's bothering them. You want to evaluate and manage neurobehavioral disorders after TBI, um, which we talked about. You want to identify what, what neurobehavioral domain is. Um, again, and we'll, we'll get to that. So number three, you want to address the underlying contributors. So I, uh, in my first slide, I talk about how I work in a sub acute and I tend to follow patients with traumatic brain injury for, you know, a year or longer. So I'm able to see kind of some of these complicated things come up neuroendocrine disorders, hydrocephalus. These are things that come about infection and infection will come, come up and it may not just be a UTI. We have to go looking for, I've seen, you know, horrible things like four years gangrene. Um, the peg is in the wrong spot. They have pain, heterotopic ossification, you know, things are going on. You want to make sure someone didn't sneak a medication in there. That's going to be problematic. Um, you know, you always want to know the side effects of your medications, internal stressors, pain, urinary retention, constipation. These are things that we deal with acutely external stressors, temperature noise. Is there room really noisy? Is there a roommate really noisy? Is there, I literally just had, you know, I was dealing with a sub acute and that my patient who just returned has somebody coming back and, um, somebody coming and, uh, you know, bothering this person in their room at, at night, another, their roommate. So we had to move him and he's doing much better. You want to have targeted pharmacotherapy. So goals of pharmacotherapy for neurobehavioral disorders and trying to get my, I'm sorry, I'm trying to minimize, there we go. The window of people that I can see in the panel there. I just did it. Sorry. Why, why are we going to use medications? And this is what, this is what I sought out to present what I was doing, but I wanted to set up that, you know, depending on where your patient is in that trajectory, you're going to want to adjust it as they move through it. Um, you know, you, your patients in PTA, you finally get them to the confusional state and you can send them home. Well, when you see them in follow-up at six months, you're going to want to, or not six months, six weeks, whatever, however you're seeing them, their meds are going to change. They're not going to need everything you sent them out with. You want to address neurotransmitter disturbances, everything, you know, that Christine had talked about to compensate for the disrupted neurocircuitry and those neurotransmitters. You want to reduce subjective distress for the patient and caregivers. This talk is a non-agitation and that's its own talk, but you want to decrease agitation. That's one of the main, uh, problems that patients and caregivers, not patients, but caregivers complain about when a patient is, uh, home. Um, it's, it's probably the number one contributed to the disability is agitation and not being able to go out in public. And you want to facilitate participation in rehab. Uh, if they're too sad or too anxious or just affected by everything going on, it's not going to help them. I once had a patient who had pseudobulbar affect. And every time we try to do swallowing exercises with him, he would be giggling and crying and we couldn't do swallowing with him. He had a feeding tube. So it wasn't until we got his pseudobulbar affect under control that we can actually get this gentleman eating. And it was just incredible to bring that to his life, you know, with the help of treatment for PBA. Remember, we expect some natural recovery from brain injury, and this includes the neurobehavioral disorders, not to say, oh, you'll snap out of it when your brain improves, you know, you want to pay attention to it, but there will be some natural recovery. Medication strategies should be geared toward reducing distress and supporting spontaneous recovery trajectory. So some general guidelines for pharmacotherapy of post-brain injury, neurobehavioral disorders, know what you're trying to treat. Understand what are you treating? Don't just throw something at it, not knowing what it is. Identify it. The person is depressed. I'm going to treat this. The person has deficits in attention. I'm treating this. The person has PBA. I'm treating this. You know, you want to identify it. You need it for your documentation. You wouldn't just say start Celexa, and don't explain why, because at least in New York state, they will come after you. Start low and go slow, but go. Yes, fine, start low dose, increase slowly, but commit to your dosing. You want to make sure that patients are getting treatment, and you commit to it. You didn't stop at five milligrams, which is sub-therapeutic because the patient said it didn't help, but you actually have to give enough of it. Make only one change at a time. Don't start a treatment for headache, a treatment for sleep, a treatment for anxiety, treatment for depression, all at the same time, because you're not going to know what you're dealing with. You have to treat one thing and keep in the back burner. We will address this the next time. Continuously reassess symptoms. It's not one and done. Look out for drug interactions. Obviously, you want to be very careful. Things aren't interacting with their blood thinners, big problems there, or giving them, you know, prolonged QT if they have a cardiac issue. And then speak to family members, care gift therapists, and hospital staff. You know, I was rounding one time in the kitchen, the food delivery person, she's wonderful. Her name is also Christine, and she told me, you know, doc, every time I deliver dinner, your patient's crying because their family isn't here, and she's always sad. So, I help her with her food, and I sit with her, and I'm like, oh my goodness. So, you know, that was something we addressed, not with drugs, but actually with environmental. Choosing pharmacotherapy and TBI. So, everything is pretty much off-label, almost. You know, FDA approval, we're not using that, but we're used to that in rehab. We extrapolate a lot of things. So, primary psychiatric literature, or we kind of hypothesize what is the neurocircuitry, the neurochemistry, you know, what are we replacing? What's the, you know, in a frontal lobe injury, what neurotransmitter are we going to try to optimize? Consider the stage of recovery. The same symptom may be treated differently at different points. You're going to treat depression different in PTA versus, you know, post-traumatic executive dysfunction. Consider side effect profiles and use them to your advantage. So, if they make a person sleepy, give them at night. Avoid meds with anticholinergic properties if they, you know, if they have a lot of cognitive dysfunction, constipation, or urinary retention. It's, you know, an 88-year-old who fell down who has BPA, I'm going to, you know, not give him probably nortriptyline or Elevil because then he's certainly not going to be able to urinate. Expect greater sensitivity to all psychotropic med side effects in brain injury. Patients' brains are different. If they were on a four, I'm coming up with something ridiculous, 400 milligrams of Seroquel as an outpatient, and they had a, you know, severe traumatic brain injury with diffuse axonal injury, that dose may be too much for them. Sometimes can use the side effect to your benefit. So, i.e. mirtazapine increases sedation and increases your appetite, give it at night. Remember, we are trying to support neurorecovery, especially of the mesocortical and mesolimbic pathways and dopaminergic pathways that Christine talked about. Sometimes dopamine receptor blockade is necessary, but aim for the lowest dose, shortest time necessary. So, breezing through this, I'm really focusing on anxiety and depression and post-traumatic stress disorder, but I wanted to point out that we have different treatments. The point of this slide is really to show you that there's different treatments for everything. So, mania, hypomania, make sure you're not confusing hypomania with depression. It may be helpful to kind of bring in a psychiatrist or a neuropsychiatrist to evaluate your patients. We're very lucky to have one at Rusk, so lucky. So, moving on. So, literature recommendations. Again, I always recommend going to the literature, but things like propranolol, these are the dosing guidelines. Its benefits is that it best treats proximal sympathetic hyperactivity, but also anxiety, tremor, and headache. So, maybe your patient actually has all of them. Obviously, watch for hypotension, bradycardia, and lethargy. Depakote or valproic acid, again, you can do really low doses. You don't have to start high. You can use it in elderly. Mood stabilizing, better side effect profile than carbamazepine, can work really quickly. You know, you got to check levels. You should always check in ammonia, especially if the patient starts acting bizarre. I've seen ammonia go up on 250 twice a day. It just happens sometimes. So, if you start a patient on Depakote, follow their platelets. Be careful. Maybe you need neurosurgery. You know, make sure they don't have something like amyloid where they're going to bleed. And you want to make sure that they don't, you know, start acting funny at one week, and then all of a sudden, their ammonia has gone up very high. You have to stop it. SSRIs, usual dosing for psychiatry, very helpful in anxiety and depression. Avoid for apathy presentations. Apathy will actually get worse with the SSRIs. It just will. It will actually make it worse in traumatic brain injury. We'll skip over antipsychotics. It's not this lecture. Neurostimulants can actually help with apathy. So, if your patient just has apathy and they're not depressed, consider something like amantadine. Depression and anxiety. Patients, you know, depression, anxiety after TBI is associated with greater cognitive and functional impairments. They can present with depression, mania, anxiety, posttraumatic stress disorder. Again, you got to distinguish it from apathy, emotional discontrol, PBA. Can be a transient feature of your post-traumatic confusional disorder, post-traumatic amnesia. So, again, you have to know where you are. The first-line treatment are SSRIs. SNRIs or TCAs, tricyclics. They're studied less because the SNRIs are newer than Prozac, Celexa, and Lexapro. The TCAs, we don't really study them that much because we use them for headache management. This is your amitriptyline. You want to be careful with those. Pamela, that's the name, because it can give you, you know, they have the anticholinergic effect and can affect your bladder and cognition. Bupropion can lower seizure threshold. So, you may not want to be starting that one. So, in PTSD, your first-line treatment is actually SSRI, SNRIs, alpha adrenergic blockers. So, that's actually an adjuvant. So, the parazacin, you know, this is going to prevent that surge, that fear surge, you know, the uncontrolled surge that patients get. You give it at night because it can make them orthostatic. Mirtazapine will help with sleep and also help, you know, again, with PTSD. Shown to be ineffective in the literature are your amitriptyline, nortriptyline, MAOIs. I don't know who's prescribing MAOIs, you know, very specific psychiatrist, not myself. Mood stabilizers, Gabapentin for gabbling, atypical antipsychotics. So, again, you know, the patient's freaking out at night. My residents like to say, make sure they're not having PTSD. They're waking up screaming, you know, are they having night terrors? What are they presenting with at night? Maybe they're screaming because they're in a PTSD, you know, terror episode. You're not going to give them Seroquel. It's not going to help them. It'll calm them down and they'll be quiet, but that's not what we're dealing with. You know, this is where it's helpful to have a psychologist who can see the patient or a neuropsychologist. Be very careful, benzodiazepines. In the outpatient world, PTSD is affiliated with alcohol use. Benzodiazepines can interact with that, obviously. Affect cognition in the long term with a traumatic brain injury and, you know, be addictive and has, you know, potential for overdose. To be very careful. I just found an article on the potential for MDMA, for adjunctive drug assisted psychotherapy. And the theory behind it is that PTSD sufferers may have increased difficulty with psychotherapy alone. Talking about the episode, it's just, you know, the triggers of going into that, you know, make psychotherapy ineffective. So really quickly, and I'm sorry for taking so much time. I could talk about this all day, all night. Psychotherapy interventions with anxiety, depression, and PTSD. It's going to be with a skilled clinician. Not, not me. I'm not a skilled clinician. You know, I don't, my patients like to tell me everything, but I'm like, we need to get you in front of a social worker, a psychologist, a neuropsychologist. You know, I also don't make very good pasta sauce. So, you know, go to an Italian restaurant, you know, and I tell them, I don't think you're crazy. There's no, it's not a red flag for me to send you this. This is part of the healing process. Your brain is getting better. And that's why these things are coming out. What is psychotherapy? Well, it's a lot of things. It could be cognitive behavioral therapy, dialectical DBT. ACT is something that they do. It's acceptance commitment therapy. It's like short-term sessions, eight sessions, individual talk therapy versus group therapy. A psychologist or, you know, a counselor will determine what the patient's most appropriate for. Sometimes group therapy can be very helpful. Sometimes the patient can kind of get lost in it. And group therapy can be for, you know, many things. They're different group therapies. At NYU, we have, you know, every group therapy under this, we have an aphasia post-stroke, post young person stroke aphasia group therapy. It's just nice to have these options. Psychodynamic therapy, that's like your Freudian. Sleep hygiene is often addressed and we'll get to that. Sorry, repeated ACT here. That's how, you know, prevalent it's becoming. Neuropsychology. Neuropsychology testing is important. If, you know, especially if you can use the results of the testing to inform the treatment. So, you know, that will tell you the person has problems with attention, processing speed, executive dysfunction. Some of your approaches for treating anxiety, depression, and PTSD may not be effective because they have such a hard time understanding it. EMDR, it's documented quite a bit for use in PTSD. And I have a few patients who go and actually get it done. It's eye movement desensitization and reprocessing. It's demonstrated benefits in PTSD sufferers across cultures. So, in the literature, but we need studies and more studies specific for TBI and PTSD. But again, I have patients who do it and they seem to be very happy. It can be very expensive. Non-PHARM treatments for anxiety, depression, and PTSD, continued physical exercise. These are things that I talk about with the patient. This is where, you know, I tell my patients do all these things. You have to be moving every day. You can't just lay in bed. You're, of course, anybody could be, anybody will get worse if they're not moving. They're not getting out of bed. They're not going outside. They're not doing anything. Physical exercise will help your anxiety, depression, and PTSD, as long as you're not exposing yourself to the triggers without addressing them appropriately. Sleep hygiene. We'll get, we'll go back to sleep. Work interventions. So, make sure they're not going back to work to a very challenging, abusive, stressful environment that is exacerbating what's happening to them. They were injured on the job and they go back to that same job where they're going to get injured again. I mean, I'm just, or they have, you know, a right brain injury and problems with attention and processing speed. And they're put in a work room, you know, on a main floor surrounded by 20 other desks with people on phone calls. You know, they're going to have a very hard time at work, get very stressed out. And if they already have anxiety about performance, they're not going to do well in that. And that's something that you can address. Eating well. If you don't eat well and nourish yourself with the correct things, you're not going to do well. And, you know, there's different things in the world and at least New York state, I know where we can help get the proper food for patients. Social interactions, outdoor activities. You need these things. You need support. Animal assisted, you know, that can be any animal program, but, you know, if you think about pet ownership, obviously you don't want the pet to be put in a dangerous spot, but pet ownership actually results in a schedule. Social interaction for social interaction. You have to take the pet on the elevator, go outside. People want to talk to you about your pet. The pet loves you unconditionally. You know, obviously you need to be appropriate to have a pet, but it's a very beneficial thing for a lot of my patients. Yoga, meditation, mindfulness-based interventions, all have been recently studied and shown to be beneficial in traumatic brain injury. One last word on sleep. Poor sleep has been demonstrated to exacerbate symptoms of TBI. The person cannot cope appropriately with their symptoms from traumatic brain injury if they're not sleeping. I can't cope with anything if I don't sleep. You have increased neuropsychiatric symptoms, inhibited participation in therapies. Patients with TBI are at increased risk of sleep disorders regardless of therapy. And then it's also been shown that patients with TBI and sleep disorders are at increased risk in anxiety, depression, and PTSD. So it's just one big miserable circle revolving around sleep. Treatment of sleep disorders. Again, I'm sorry, that's a whole nother lecture, 90-minute lecture. So in conclusion, understand where your patient is in TBI recovery spectrum. Understand where are they? Are they in PTA or are they, you know, 90% recovered and now dealing with anxiety, depression, and PTSD? Use, you know, history and mental status exam to identify, you know, what we're dealing with to target that therapy. Look at their brain injury. Look at the imaging. What pathways do you think are disrupted? Is it the cerebellum or the frontal lobe? And maybe the whole thing. Look for underlying neurological medical contributors always. Physiatrists are very good at looking at that. I, you know, I will challenge the neurosurgeons and say, there is something there, there is, you know, we're dealing with something here. There's swelling, whatever. I'm going to get the CAT scan. They're like, don't get the CAT scan. We get the CAT scan and there's something there. Actually, they love getting CAT scans. I shouldn't say that. When using medications, know your rationale. Why are you using it? Can we use the side effects or the side effects to our benefit? Are we going to treat the headache, anxiety, and the elevated heart rate all at once with propranolol? Maybe that's going to be awesome. Use literature, start low and slow, go slow, but go commit to your dose. Make one change at a time and involve your patient and the caretakers and, you know, these decision makings, nothings. There's no silver bullet. There is no FDA approval. So you want to manage their expectations and get approval for making these medication recommendations. Okay. So thank you so much. We're going to open it up for questions and let's all come back and I'm so sorry about the time, but I'm hoping we can talk and answer any questions. So Christine, Dr. Zorich, we're all here to chat with you. So we do have a Q&A session later on. And again, like no question is unwelcomed. You know, we're so happy to talk to you today and, you know, thank you for, you know, for some of us, it's nine o'clock. You know, if nobody has any questions, we can end. And, you know, physiatry is a very small world. You guys know where to find us. Okay. Let's turn it back over to Brian. I think you wanted to talk about the session in four weeks. Yeah. Yes. So thank you for everybody for participating. This has been great. Again, we will close out tonight, but then I will be sending a follow-up information regarding the Q&A follow-up on the 30th with information on how to access this recording and evaluate it on there. So thank you, everybody, and have a good night.

mood disorders

brain injury

depression

anxiety

post-traumatic stress disorder

diagnosis

epidemiology

pseudobulbar affect

rehabilitation