Transcript for:
Understanding Anxiety and Neurotransmitters

Hey everyone, it's Dr. Wood and today we're going to be discussing our module 3 section today on anxiety. So, let's get into it. Alright, this week's neurotransmitter spotlight is going to be on GABA, or gamma-aminobutyric acid, as it is also known by its chemical name here.

So, GABA is really important. This is... used primarily as the major inhibitory neurotransmitter in the brain and they will find that medications that can affect GABA can be used for all kinds of things not only like anxiety like we're talking about today but also for conditions like seizure disorder muscle relaxant purposes all kinds of things here now GABA actually is being made from glutamate and if you know anything about glutamate which will have its own section a bit later on glutamate is the major excitatory neurotransmitter so it's interesting how there's this sort of interplay where you have the excitatory neurotransmitter being converted into GABA the major inhibitory neurotransmitter and this process here does require vitamin b6 which is why sometimes if patients have very severe b6 deficiencies for example they can actually in some medications can do this too like isoniazid for tuberculosis can deplete b6 and basically make it so you cannot produce GABA And you get this imbalance where you get too much glutamate, too little GABA, and seizures is actually one of the big things that can come about from that. But once we have glutamate converted into GABA, it is then stored in the vesicles within the presynaptic neurons where it can be released down the line whenever it is necessary to do so.

We will find there is some GABA reuptake that occurs here to some degree, these GABA transporters, and we also find that the enzyme GABA transaminase is responsible for metabolizing this. back into glutamate where it can then be recycled and used over again generally speaking the function for gaba and there's two primary receptor types we'll talk about gaba a and then gaba b gaba a is primarily inhibitory you're going to see when this gets activated this opens and allows chloride to flow into the postsynaptic neuron and what that's going to do is basically hyperpolarize it just make it more difficult for an action potential to occur which is why it makes sense that it would treat things like seizures because it's basically like Um, just inhibiting the neuron and keeping it from firing, which is that's what a seizure is, is abnormal firing of those neurons there. Um, you'll find this throughout the CNS and used for a lot of different purposes here. GABA-B is typically where you're going to see a lot of like your skeletal muscle relaxants work, like baclofen, tizanidine, et cetera. And so these can have a little bit more variability in terms of what type of receptors are going to be hitting here in terms of the secondary messenger systems and whatnot.

Uh, I don't want to get too down the rabbit hole on this one since it's not going to come up as often clinically. Okay. at least for our purposes for psychopharmacology here.

So we're mainly going to focus on GABA-A and the medications that can sort of affect that. In this section in particular, we're going to discuss it in the context of anxiety. So what are the clinical effects of GABA?

If you were to have, say, an increase in GABA activity, you'd expect to see decreased arousal, sedation, and go along with that. And one of the benefits you'll see is this sort of anxiolysis that can occur, so it'll help to decrease anxiety feelings patients may be experiencing. In some cases, we may be using this as helping with GABA to produce some amount of amnesia. So for instance, if we're sending patients back for surgery, we may try to give medications and enhance GABA in order to allow for some degree of amnesia to occur. So they don't remember being really anxious around that time of surgery, and they just kind of wake up in recovery, and they're kind of good to go.

At really high doses, we can see issues of respiratory depression, and you'll see this is where medications are going to play a big role here. And to go along with that, agents that sort of enhance the actions of GABA can include a lot of your sedative agents here. So this can include things like benzodiazepines.

Ethanol is a really big one that helps to enhance GABA activity. I didn't put it on here, but the barbiturates as well, things like phenobarbital, which you see more often used for seizure purposes, also is pretty heavy in terms of enhancing GABA activity. And sort of secondary to that, we can see things like muscle relaxants. I mentioned they work at the GABA B receptor. They also tend to have pretty sedating effects and then opioids as well.

And we'll talk more about chronic pain management and addictive issues and whatnot later on. And we oftentimes will see a lot of co-ingestion of medications that can increase the side effects of each one of those. So, for instance, patients frequently are on sedative agents like benzodiazepines. They're on opioids for chronic pain.

And then they're drinking alcohol and they just tend to synergize really well with another. They can get patients into pretty big trouble. especially when it comes to that respiratory depression that we sort of mentioned there. Agents that would mitigate the actions of GABA tend to be stimulatory in nature.

I mentioned glutamate sort of being the mirror image of GABA in terms of it being the excitatory neurotransmitter, but we oftentimes find stimulants like cocaine and amphetamines and whatnot are able to counteract that effect to some degree. And interestingly, I remember several years ago, there was an alcoholic beverage that came onto the market called Four Loko. And Four Loko came in a really big tall boy can, and it was something like, it was malt liquor, and I think it was something like 12 or 14% alcohol by volume. So pretty hefty dose of alcohol into this container here.

But the kick with Four Loko was, is it actually contained caffeine, which is a known stimulant. And so it got into really big trouble with the government because... You'd have these younger people who may have been inexperienced drinking alcohol, slamming these really high percentage alcohol by volume drinks. And whereas normally if they were just consuming alcohol, then they would have had the suppressive effects. They would have had the sedative effects.

They probably would have passed out, right? Well, unfortunately, having the caffeine in with the 4-Loco, you end up finding that these patients were staying awake for longer, and then they're able to go and do a lot of really. dumb things like go and drive cars and things like that. I actually had a pharmacist friend whose little brother during this time snuck a Four Loko and ended up driving his car.

And when he woke up, he was actually faced the wrong direction on an off ramp for the interstate. Fortunately, everyone was alive. So they ended up having kind of telling the company, hey, you better take the caffeine out.

Otherwise, we're going to make you. So nowadays, the stuff you find is just the alcohol. But a little interesting sort of interplay here between your sedatives versus your stimulants and sort of how they can interact with one another.

to some degree there. All right, so let's get into our anxiolytic drugs here. So with anxiety disorders, we can find that this is going to be broken up into a wide variety of categories, whether you're dealing with just more generalized anxiety issues, whether you're dealing with more issues of PTSD or OCD specific phobias, you'll tend to find a lot of overlap in terms of management here. So I will talk about some specific situations like social anxiety disorders.

or like performance anxiety issues and how that might be treated a little differently but largely speaking you're going to find that the pharmacologic management of these will be similar obviously using your non-pharmacologic therapies in addition to your meds are going to be absolutely synergistic and almost mandatory in a lot of cases to help patients process through a lot of these issues especially there is like a really focused event or specific phobia they happen to be having issues with Now anxiety is basically this maladaptive response. Now anxiety is really useful in certain situations. It keeps you on edge so that if a tiger or something was trying to hunt you, you would be very on edge and be able to activate that fight or flight response, right?

So unfortunately, though, when you're just anxious all the time or anxious at really inappropriate things, potentially, this ends up leading to this sort of maladaptive sort of process here. And so this is what we're going to try to interrupt. So we're going to see this is an issue of both norepinephrine, which we see basically flooding the patient's system when they're having anxiety because your fight or flight response is sort of on overdrive.

Serotonin can play some role here, and certainly GABA as well can help to ameliorate or reduce those symptoms of anxiety by basically trying to basically take a chill pill when we get into the medications here in order to help deal with that sort of anxious sort of responses there. This can also lead to issues as well because as you're having this increase in stress and anxiety, you end up finding that the adrenal gland is going to be pumping out a ton of cortisol as well. You might experience that being in this program perhaps and being stressed out around test time and all that sort of thing there.

Cortisol levels go up and that has a whole host of effects on the patient including effects on their blood sugar and their blood pressure, their weight, etc. Again, it can be a pretty sort of... Interesting sort of overlay of different things that are happening here, but if we can deal with that maladaptive response, it can help to sort of deal with all the other downstream sort of effects we're going to run into.

So it's important to understand many medications can actually induce symptoms of anxiety, and if you can try to get rid of these if a patient is potentially using them, that can be one easy way to fix the problem here, although you may not always be able to do so. We'll get into some of our antipsychotic medications a bit later, but a common symptom that can happen from these medications and something we talked a bit about with the SSRIs last time is this feeling of akathisia, right? This is the sort of ants in your pants.

You just can't sit still. You just want to just get this nervous energy out. That can be a common side effect with a lot of your, especially first-generation antipsychotic medications.

A lot of your stimulants and sympathomimetics with things like cocaine and amphetamines we've mentioned before. In some cases, patients taking hallucinogens may have a really bad trip. So things like lysergic acid, diethylamide, which is LSD, psilocybin, which you can find in magic mushrooms, and even things like dimethyltryptamine or DMT, which is pretty popular nowadays in terms of the hallucinogen sort of, you know, what is in vogue nowadays. Patients can have really bad paranoid sort of episodes while taking these. uh that can manifest as sort of acute anxiety panic sort of attacks here and along with that things that can just cause symptoms of anxiety so that uh you know feeling of a racing heart um you know pounding in your head sweating uh tremulousness things like stimulants we mentioned before can cause these symptoms here a lot of anticholinergic drugs so a lot of your um like first generation antihistamines like benadryl can do this um your tcas can do this uh you know a whole host of different medications that block muscarinic receptors blocking the acetic choline causing these symptoms here.

Another big one that we would frequently run into is actually drug withdrawal. So patients who are withdrawing from sedative agents can tend to manifest a lot of symptoms of anxiety because their body is sort of being deprived of that substance, which they had become dependent on over time. We see this a ton with ethanol for patients, especially if they're like being admitted to the hospital for something unrelated to their alcohol use disorder.

And all of a sudden they're cut off from their source. they can then start to manifest a lot of these symptoms of anxiety, both physical and mental. Same thing with opioids and benzodiazepines as well.

And so that's an important question to ask. And of course, patients may not be always forthright with you, but it's an important consideration for sure. So obviously supportive care is first-line therapy for these patients here.

And we'll find that pharmacotherapy is going to be better used to manage things. And we'll see how different medications can affect different. sort of phases of the anxiety, right?

Especially if you have a whole anxiety disorder. For acute anxiety issues, panic attacks, things like that, benzodiazepines are going to be our best friends. I'm going to go into depth on those here in just a minute.

For chronic management, typically our antidepressants are going to be playing a role here. So either your SSRIs, SNRIs, maybe even TCAs is sort of like a third line kind of agent there. And that's what I mentioned last time was that a lot of your symptoms of depression can be overlaid by some degree of anxiety and they can sort of co-mingle with one another.

Even if the patient doesn't have a full diagnosis of a whole anxiety disorder, they can still be quite anxious while depressed. And that's why we see that the antidepressants are nice because they can have benefits for both in a lot of situations there. We'll talk about as well, alternative agents like buspirone, and I'm going to save the antipsychotic agents when we talk about schizophrenia later. But generally speaking, these are the meds we're going to be talking about today. So a little bit of retread with antidepressants.

We'll have some new agents here as well. So we're going to see these are effective. At least antidepressants are good for acute and long-term management of generalized anxiety disorder.

Just keep in mind, again, the same caveat applies here is that these medications do not kick in immediately. It will take some time, maybe even up to six weeks to see the full effects of the actual meds here. You can certainly see effects sooner than that.

But, you know, by the time you get to that six-week mark, if you don't see any kind of improvement yet, the patient probably needs to be switched to something else. And so things that actually have FDA-approved indications can include drugs like your venlafaxine, duloxetine, which those both fit into your SNRI category, and then things like paroxetine and escitalopram. It's not to say that the other ones can't also be used for anxiety disorders. They certainly can, it's just they may not have an FDA-approved indication. So they're used off-label, but you have lots of evidence to back you up to say, yeah, it makes sense to try using something like fluoxetine, for example, for patients with anxiety issues.

Imipramine and some of your other TCAs can be sort of used as a second or third-line agent there. However, due to the higher adverse effect rate, due to things like the alpha blockade we discussed, blocking of the muscarinic receptors, etc., we'll try to hold off on those as best we can and try to stick with the cleaner mechanisms of the SSRIs or SNRIs. Again, we're not really sure why this is working for anxiety disorders. Maybe it's thought to activate some of these stress-adapting pathways.

And again, we mentioned it's going to take several weeks. And of course, we talked about the adverse effects previously, so that still applies here as well. So just like we talked about. For instance, like QT prolongation with acetalopram and citalopram.

We talked about, you know, issues like having, you know, a little bit maybe worse in hypertension with some of your SNRIs like venlafaxine, for example. So that stuff still applies here. It's just we're using it for a potentially different purpose.

Or maybe using it for both conditions at the same time, depression and anxiety, depending on the patient's situation. So let's look at our benzodiazepines. This will be the newest and kind of biggest class we'll talk about today and very helpful for managing not only seizure disorders, anxiety, muscle relaxation, all kinds of purposes here we're going to see for the benzos.

And what these do basically is they're going to be working as what they call an allosteric modulator, a positive allosteric modulator, a PAM they sometimes call it. And these potentiate the effects of GABA. Basically what you're going to find is here's the GABA channel here.

Normally GABA is going to bind at this site and it does so you know somewhat regularly but when you have the benzodiazepine receptor binding site occupied here it makes GABA bind much more readily so it's just much more likely to bind to the receptor and then there it opens up and allows chloride to flow in just like we talked about before. Again this is a GABA A channel that we were talking about before that's the main one the benzos are going to be affecting here. So the benzos don't open up the channel itself they just help GABA to work that much better they facilitate GABA basically. We have a lot of drugs in this category here. And again, these are widely used.

A lot of patients may be on these chronically. And we'll talk a little bit about development of tolerance and physical dependence and things like that. I believe these are the first ones we're seeing so far that are actually controlled substances. I take that back, actually.

Ketamine was the first one. These are all going to be on your C4 category. So there is some restrictions for prescribing. Generally speaking, you can't do more than...

say, six months worth of the medication at a time. So say if you're writing for a monthly amount, you know, the initial fill plus five refills. So there will be some restrictions there as opposed to something like, you know, your SSRIs, for example.

So just to go through the list here, we have things like alprazolam, we have chlordisopoxide, we have clobazam. This one I used a bit more in like pediatric epilepsy and neurology. Clonazepam, chlorazepate, diazepam. lorazepam, midazolam, oxazepam, temazepam, and then triazolam.

So there's a lot of these, and they actually have a lot of different sort of idiosyncrasies when it comes to how they're being metabolized, if they're fat or water-soluble. I'll talk a bit more about that in a second here, but one thing I wanted to bring to your attention are the four agents I have starred here. Now, one of the big problems you find with benzos and elderly patients in particular is that they... tend to have a lot more kind of dramatic effects of these medications. So they get more sedated from this.

They may have more altered mental status. It may seem like they're having worsened dementia. And so we want to have benzos, if they're necessary for these patients, to have a much cleaner sort of pharmacokinetic profile. And what I mean by that is you want agents that are more water soluble, meaning they're more likely to be filtered through the kidneys to be eliminated in the urine.

And you want things that don't have a lot of active metabolites. One of the problems you're going to run into is that when they get broken down in the liver, they get turned into another active form of a benzo, basically. They can cause further sedation and things like that.

So the benefit of using water-soluble agents with no active metabolites is that they leave the system relatively quickly, assuming your patient has relatively okay renal function. Otherwise, patients with hepatic dysfunction, they tend to accumulate this stuff. If you're using fat-soluble agents, these tend to accumulate into the fat tissue. And so you can have much longer durations of action for these medications in your elderly patient than you might expect.

So the four agents that have that sort of cleaner kinetic profile, I call them the lot benzos. So lorazepam, oxazepam, temazepam, and then triazolam. So if you're going to use a benzo in an elderly patient, these tend to be preferred because they're less likely to accumulate in these elderly patients and cause that worsened mental status, et cetera.

So as I mentioned, there are plenty of other uses for benzos, seizure, acute agitation, muscle relaxants, sedation. I mentioned using in the surgical realm before patients go back for surgery, usually they get a dose of something like midazolam or Versed, and that's useful because it causes some of the anterograde amnesia, similar to how alcohol causes like brownouts and blackouts with your memory. These are doing very similar actions.

They both potentiate the effects of GABA there. So the kinetics, as I mentioned, is going to be related a little bit to how we're using these agents here. So looking at the onset of action, obviously the benzos have to get into the brain in order for them to work. So things that have a higher lipid solubility tend to cross more easily and can have a faster onset.

So maybe within 30 minutes to 60 minutes or so. So much faster acting than we're going to see with our antidepressants, meaning these are good for having acute anxious issues, panic attacks, things like that. These work relatively quickly, so you're going to get much more kind of rapid and intense effect, but you may end up seeing a shorter duration of action with these here.

So that's one thing to kind of note. Things like oxazepam that has lower lipophilicity, meaning higher hydrophilicity, may take longer to cross the blood-brain barrier, but once it's there, it kind of stays around for a longer period of time and, again, doesn't tend to accumulate into the fat tissue like you may see with more fat-soluble drugs there. Obviously, we have many routes that we can give these medications. PO is going to be slower.

but is more suitable for outpatient use. We use a lot of IV benzos for sure for patients having acute panic or anxiety issues. We even use, at least in the PDR, we use a decent amount of intranasal midazolam. That's one really nice way to be able to get some anxiolysis for your patient. Maybe they need a needle stick or they're going for a procedure or something.

We would do intranasal midazolam if we didn't have an IV established. And that was a really nice way to try to kind of take the edge off a little bit for the patient. make themselves a little bit more comfortable there.

There's also a lot of SIP interactions that you run into, especially when it comes to the benzos. In particular, they tend to be substrates for SIP3A4, meaning if the patient happens to be taking another SIP inhibitor or an inducer, it can really affect the kinetics for these benzos, causing them to have much more dramatic or reduced effect, depending on the interaction there. So like a SIP3A4 inhibitor would cause the benzo levels to elevate because they're not being metabolized as quickly.

I mentioned there again the exceptions here being lorazepam, clonazepam, and oxazepam. Two of those we saw on that lot list there of the preferred agents in elderly patients. Typically, if they have liver dysfunction, they cannot metabolize these as well, so they stick around for longer. And a lot of them do have active metabolites, meaning, again, that further extends the duration of action.

Probably okay for younger people who have decent organ function, but for these elderly patients, it can really throw them for a loop there, causing dizziness and falls and fractures and all kinds of things like that. So adverse effects-wise, the biggest thing you should expect to see, which makes sense based off the mechanism, that's what we're using it for generally, is drowsiness, sedation. some psychomotor impairment and ataxia patients will appear sort of drunk when they're using these depending on the dose and how sort of tolerant they are to those effects there initially you'll get a lot of that sedation effect but tolerance does develop over time the body just sort of gets used to having that drug around and then that's sort of the status quo for these patients here interestingly for some patients who are getting like a benzo for the first time they may even have what they call paradoxical excitation we see this sometimes in kids and rarely in adults But basically, you give them a dose of a benzo, and all of a sudden, they are bouncing off the wall. They get the akathisia really bad, and they're just going crazy. And it's like, what is happening here?

This sort of sedated the patient, but now they're really kind of bouncing off the walls. And so usually, more benzos will fix that problem there. But it's just kind of an interesting little idiosyncrasy you might see for some patients because it's very unexpected there.

I mentioned the memory impairment, which can be a good thing if patients are going back for surgery, as an example. Um, but in some situations it could be bad things. So if like, for instance, in situations where a patient's drink was spiked with a benzo, that could be, you know, one big issue in terms of causing anterograde amnesia for those patients there.

Um, and these are very synergistic with other CNS depressants, alcohol probably being the most common co-ingestion with the benzodiazepines. And in fact, I knew a girl one time, I remember in way back in the day in undergrad, she was like, oh yeah, I'm always a cheap date whenever I go out drinking because I just take a benzo. before I go. And then I only have to have a drink or two and it's fine.

I'm like, Oh, yikes. Um, but yeah, that's, that's a very common co-ingestion. It's very easy to find. Patients can definitely overdo things when they start to have those inhibitions sort of starting to, to loosen a little bit there. Um, one thing, you know, in terms of safety wise, one thing I was always tall told in fellowship, they're saying, you know, the only way you can really die from a pure oral benzo exposure.

is if you get hit with a truck that came to deliver it to you and it goes to show you that you know you're very unlikely to die just from a pure benzo exposure but the unfortunate thing is is patients have so many co-ingestions opioids being a big one ethanol being a really common one and then your muscle relaxants cause chronic pain patients maybe self-medicating with alcohol they get into real serious situations in terms of causing risk for things like respiratory depression that may need to be intubated can be really significant there The other thing to know as well is that patients chronically on benzos, I mentioned they have tolerance that they develop over time, but they also develop a physical dependence, which is very common to see here. And if you have patients withdrawing from this, they can have some pretty significant side effects from this. So agitation, tremor, sweating, seizures in some really severe cases here. And so that's really the biggest thing we worry about.

This is something to where patients who are having a benzo withdrawal, that's possibly fatal you know opioid withdrawal you know patients will probably feel like they want to die but with a benzo withdrawal and alcohol withdrawal as well since they're kind of so related um definitely definitely you can see these uh withdrawal seizures and and really the only treatment is more benzos at that point there so again it's kind of self-defeating to some amount um a lot of rebound anxiety i can tell you for sure the most anxious patients i ever saw uh the few times i worked retail and and in my pharmacy school days was patients coming to the pharmacy And they were out of their benzos, usually Xanax, and they had a refill too soon. And just that like look of dread on their face when I said, I can't give you anything right now because you're too soon. So a lot of rebound anxiety because they knew that withdrawal phenomenon was going to come on.

And so a very kind of unfortunate situation there. Best thing to do is to titrate them off slowly, right? So if you can kind of build into some kind of taper, use agents with longer half-life or have active metabolites, that can certainly help for sure. But again, this can be quite dangerous.

Now me being a toxicologist, I always like to note when things have antidotes available to them because it can be potentially life-saving. This one I'm not quite so in love with here. So we do have a benzo antagonist.

So it's a benzo receptor antagonist here called flamazenil or romazicon. And so this can be used sometimes for patients who maybe are slow to recover after surgery. You can kind of wake them up a little bit faster.

If I have little kids that accidentally take mom or grandpa's benzo. that's relatively safe to do because those patients are otherwise sort of benzo naive. You really don't want to use this in patients who are potentially chronically on their benzodiazepines because of that potential for putting them into withdrawal seizures.

So generally speaking, if we have like a true benzo overdose, we just give them time to sleep it off because even this enhanced recovery is not worth the risk of potentially causing seizures, which as I mentioned, the only treatment is more benzos at that point there. Now, it can be difficult to discern a benzo withdrawal from other agents like opioids and sedative hypnotics. They all appear pretty similar in their presentation. Anxiety, agitation, they're very irritable, maybe some GI hyperactivity here.

As I mentioned, the key exception, the key difference here is opioids, no withdrawal seizures, so relatively survivable. Like I said, they'll feel like they want to die, but they're not going to die. Sedative hypnotics like alcohol, benzodiazepines, you know, barbiturates.

Those can cause a withdrawal seizure because their brain is so used to having all that extra gab activity. Then when you withdraw that, all of a sudden glutamate takes over and that's so excitatory and ends up causing those seizures there. So just something to kind of make note of.

Moving on, the other agent we may use as sort of an add-on sort of adjunctive sort of agent is buspirone. This is a non-benzodiazepine anxiolytic. It doesn't have any anticonvulsant properties, no hypnotic issues, no dependence issues.

So this might be useful for patients who have a history of substance use disorder, who you're more hesitant to give a benzodiazepine to since that can possibly cause relapse of their symptoms depending on their, you know, their potential susceptibility to that. No impairment properties as well, so I'm not really worried about someone getting in the car and driving on buspirone, but I am if someone's taking, you know, Xanax for the first time here. Generally due to kind of inconsistent efficacy here, it's going to be considered sort of second line, and it does take a couple of weeks to kick in.

So overall, I would not say this is going to be a slam dunk for any of your patients there by any means. Now, again, we don't know the full mechanism for how this works, but we do think it's partial 5HT1A agonist. So by activating this receptor, you may actually inhibit further firing of serotonin.

Again, beyond that, we're not really sure what the overall effects are going to be as a result of that. Pretty well tolerated. And again, that kind of goes with it not being super effective as compared to things like your benzos and SSRIs. You may see some dizziness, nausea, headaches.

This is also metabolized by CYP3A4, so it is subject to those drug interactions if patients happen to be taking a CYP3A4 inhibitor, like a macrolide antibiotic like azithromycin, for example, or Zithromax. One thing to kind of switch gears a little bit and to discuss a specific sort of anxiety would be more of a social anxiety or a performance anxiety sort of situation here. And this is where beta blockers can come into play.

And basically what these are going to do. And if you imagine if you had something like a big event to give, you had to go give a presentation in front of a room of, you know, world renowned physicians, you might be pretty worried about that pretty anxious. I think public speaking is still one of the most common phobias out there in the world. And so what you can find is, yeah, you could probably drink some alcohol. You could probably take a benzo, but that's going to cloud your, your mental function, right?

That's going to impair your mental function. And you want to be on your game. You want to be able to speak clearly in your mind, be clear, not have any of that inhibition there, right? So what beta blockers do is they blunt the physical manifestation of anxiety while maybe not necessarily reducing the anxiety you're feeling up in the CNS here. So it reduces the effects of those endogenous catecholamines, things like norepinephrine they're spilling out as a result of that fight or flight response being really kicked up here.

So if you're having sweating, tachycardia, tremor, blushing, this really helps to reduce a lot of that. So you may feel nervous up here, but elsewhere you're not going to really be showing it there. So good for performance-based or social situations. Some typical agents to use here include things like propranolol or atenolol are used pretty commonly here.

I think propranolol or inderol is probably the most common one you're going to run into just because that's pretty good CNS penetration since it is pretty lipophilic there. Generally speaking, you take this one hour prior to the performance or event. And then one thing to know is like, don't have them take it the first time before the event. They probably want to try it at least a test dose at home. in order to determine adverse effects and determine tolerance.

You wouldn't want someone to take, you know, preparing a lot for the first time before the event, and all of a sudden their heart rate bottoms out into the 40s and they pass out due to hypotension, right? It probably would be a bad situation there. So do a test dose at home, and then an hour before the performance or event, and then typically speaking, they're kind of good to go there.

So generally speaking, if you need more, if you're having more urgent symptoms, Typically, you can start off the short-term course of a benzodiazepine, maybe two to four weeks or so, and then start up your SSRI or SNRI therapy and kind of assess kind of what else is going on with the patient there. If they're not having any kind of acute urgent symptoms, you don't necessarily require the benzodiazepine. You can just get them started on an SSRI or SNRI as appropriate there. Of course, if they're not having an adequate response to therapy, you can switch to another agent within the class. You know, don't...

Think you have to try every single SSRI under the sun before you switch to something else, another class, you know, maybe try one or two and then try switching it up. And of course, always try to figure out what patients have been on previously to they've responded to as well. Typically, they've gotten no adequate response at that point, then we can consider using other TCAs like amipramine as an example.

But again, side effect profile may be worse for those patients, but it may work for them. So who knows? So that'll do it here for this section.

Thanks so much for joining me. If you have any questions, let me know. Otherwise, I'll see you soon. Thanks a lot. Bye.