Cram The Pance - S1E52 Antidepressants (SSRI, SNRI, TCA, MAOI, Atypical)

Episode Date: November 26, 2023

High Yield Psychiatric Medications Antidepressants Review for your PANCE, PANRE, Eor's and other Physician Assistant exams. Review includes SSRI's, SNRIs, TCAs, MAOIs, Atypical antidepressants, Serotonin modulators. TrueLearn PANCE/PANRE SmartBank:https://truelearn.referralrock.com/l/CRAMTHEPANCE/Discount code for 15% off: CRAMTHEPANCEIncluded in review: Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Desvenlafaxine, Duloxetine, Levomilnacipran , Milnacipran, Venlafaxine, Amitriptyline, Clomipramine, Doxepin, Imipramine, Trimipramine, Desipramine, Nortriptyline, Protriptyline, Tranylcypromine, Isocarboxazid, Phenelzine Selegiline, Bupropion, Mirtazapine, TrazodoneBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right, so today we're going to be talking about antidepressants. Thank you, everybody who's supporting the podcast, the really nice comments, everything I really appreciate it, and thank you so much for today's sponsor, True Learn. So let's talk about antidepressants, SSRIs, SNRIs, TCA's, MAOI's, atypical antidepressants. There's a lot to know here, so I'll keep it as high yield as possible and throw in a bunch of mnemonics to help you remember what you really need to know. Before we get started, let's really quickly talk about a couple basic fundamental concepts that will help you better understand the meds will go over today.

Let's start with the monoamine hypothesis. So the monomene hypothesis dates back to the 1950s, basically states that the underlying pathophysiologic basis of depression is essentially a depletion in levels of serotonin, noraphenephrin, or dopamine in the CNS. Now, we've learned a lot over the years, and we know that's not all that's going on. There's definitely more to it than just a chemical imbalance. But understanding this basic concept, it's going to help you better understand the meds will go over today and their proposed mechanism of action.

So before we start with the first class of meds, let's really quickly run down this whole neurotransmitter exchange in the brain. So we have two neurons close together. One neuron is the presynaptic neuron. The other is the postsynaptic neuron. They're separated by a teeny tiny space called a synaptic left. So the presynaptic neuron, it's got all the goodies, depending on which type of neuron we're referring to, serotonergic, etc.

It's stocked with either dopamine, serotonin, or epinephrine. And they're all stored in these sack-like. structures called vesicles. So eventually we have to get those neurotransmitters out of those vesicles so they can do their work. So what happens is an action potential zaps this presynaptic neuron, which causes these vesicles to open up and dump their delicious contents into that presynaptic cleft between the two neurons. At this point, those neurotransmitters, dopamine, serotonin, et cetera, they bind to the receptors on the post-synaptic neuron and then they work their magic. After a period of time, though, the neurotransmitters that are still hanging out in the

synaptic cleft, not really doing much. Body's got a clean. them up. So some of them will just drift off in a process called diffusion. Other cases, they'll be sucked back into that presynaptic neuron and potentially broken down by an enzyme known as monoamine oxidase. A lot of the meds will go over today impact this specific area, inhibiting that cleanup process. Some meds block the reabsorption of those neurotransmitters, allowing them to hang out in the synaptic left for longer. Some meds block monoamine oxidase. So those neurotransmitters aren't broken down. It can be recycled for another go. And we'll dive deeper into that once we break down each individual class of medication. So that's the basics. Now that we have

that covered, we'll get started. And we'll start with arguably the most important class of medication to know for psych. And that's your SSRIs. Our selective serotonin reuptake inhibitors, if you're going to focus on one class of medication for psych, let it be SSRIs. If you get a question and it says, which is the first line med for the psychiatric disorder, and you can't remember which med it is, pick an SSRI and you got a good chance of getting it right. So the meds in this class are cetalopram, eschatalopram, fluoxetine, fluvoxamine, peroxatine, and certraline. It's a lot of weird and similar sounding meds. A lot of these antidepressants are just really difficult to memorize, as they all sound so similar. And usually I don't recommend taking the time. But for SSRIs,

this would be the one time where I would make an effort if you can because they come up so often and it's good to be familiar with them. So if you do want a way to memorize them, I do have a mnemonic. So when you think of SSRIs, I want you to visualize for now on is a snake charmer. Those guys who play that flute that makes the snake come out of those little baskets, that's what you're going to associate with SSRI medications from now on. Think of a snake charmer sitting down. He's got a parrot on his shoulder, oddly enough. He's playing the flute. And the snake, also known as a serpent, is slowly escaping the basket. Again, snake charmer sitting down, parrot on his shoulder, playing his flute, the serpent is escaping the basket. So sitting down

should help you remember sitalopram, not the same spelling, but same pronunciation. Parrot should help you remember paroxetine. And the parrot on his shoulder, by the way, is really fat, because paroxetine is the SSRI associated with the most weight gain of all of the SSRIs. And he's playing as flute. Flute helps you remember fluoxetine and fluvoxamine. And then the escaping serpent, remember, serpent slowly escaping the basket. Escaping helps you remember eschatelopram, and serpent helps you remember certuline. All right, hopefully that helps remember Snake Charmer every time. me hear about SSRIs. Now that we know the meds that are in this class, let's talk about how they work. Well, the name certainly helps with that. SSRI stands for selective serotonin re-uptake

inhibitor. So SSRIs selectively inhibit the re-uptake of serotonin. So let's start with the word selective because that's actually really important. This class of medication has relative little affinity for other types of receptors besides serotonin. Unlike some of the other meds will go over today that target a bunch of other areas, often causing a number of unwanted side effects. The selectivity of this class, it's part of the reason they're so well tolerated and have a relatively benign side effect profile. It's also the reason they're preferred over other classes quite often. So selectivity definitely important. Now, how do they inhibit the reuptake of serotonin? Why does this matter? Well, we talked about this briefly before. So SSRIs do this by

decreasing the action of that pre-synaptic re-uptake pump, that pre-synaptic serotonin re-uptake pump. So they essentially block the removal of serotonin from the synaptic left for a period of time. It's like if there was a big vacuum sucking up all the serotonin from the synapse, SSRIs just come in and plug that up. So in turn, we have more serotonin hanging around for longer. And it was originally hypothesized that more serotonin meant improved mood, and that's how these meds worked. And it was so simple.

But in actuality, it's not that simple. And we later realized there's more to it than that, because if the effect of SSRIs were solely based on the fact that they just inhibit re-uptake of serotonin leading to increase serotonin levels, they'd be affected from day one as serotonin levels increase very rapidly after taking the first dose. But in actuality, the full therapeutic effect of SSRIs usually takes many weeks to manifest. So we know something else is going on here besides the increased serotonergic activity. And I don't think you need to know this for your exam, but it's believed SSRIs also increased production of neuroprotective proteins. They can modify.

phy serotonergic receptors and these added effects which occur in the weeks following initiation of the medication are thought to be the reason for the delayed therapeutic benefit. So for the exam, remember these drugs selectively inhibit re-uptake of serotonin, leading to increase serotonin activity in the CNS. But for real life, realize there's more to it than that. All right, now let's talk about the indications for these meds next, starting with major depressive disorder, unipolar major depressive disorder. So when we're talking about pharmacologic therapy for treatment of depression, SSRIs are usually going to be your first line agents. Now, depending on the comorbidities the patient has, in some cases, SNRIs, a typical

antidepressants and serotonomodulators that will go over later, they can be reasonable alternatives to SSRIs for initial treatment, but in general, most patients you're going to start with an SSRI. So some other indications for SSRIs are generalized anxiety disorder, panic disorder, post-traumatic stress disorder, premenstrual syndrome and premenstrual dysphoric disorder, obsessive compulsive disorder and then bulimia nervosa but specifically fluoxetine so bulimia is another indication for ssris specifically fluoxetine though is what you should remember as it's the only fda approved med other ss can be used second line but the only first line fda approved med for bulimia is fluoxetine so this is such an easy test question i know i got it and you'll probably be asked this um so how can you

remember this i have a mnemonic it's not perfect but it's going to at least help you down narrow down the choices on an exam question. So bulimia has the word bull in it. So a bull is a cow with horns. And then fluoxetine has the word ox in it. And ox is just another type of cow with horns. So when you see bulimia, think of an ox as in fluoxetine, the other cow with horns, bulimia, fluoxetine, bull, and an ox. The only crappy part about this mnemonic is there's other meds in this class that have the word ox in them, peroxitine, fluvoxamine. But the rest of the SSRIs do not. And a lot of the other classes don't. So it's going to at least help you narrow it down on the answer choices. So when they ask you, what's your first line med for

bulimia, be thinking of a bull, then remember your other cow with horns and ox, and then make sure you look for a med with the word ox in it, and then you can narrow it down that way. So there's some other indications, but those are the main ones you'll likely be tested on, and that's what you should be aware of. Let's next move on to our adverse effects. So because SSRIs are so selective, as we discussed before, mainly just affecting the serotonin receptor, and not messing around with the other stuff, like the colonergic receptors, exception being proxatine. Anyways, because of the selectivity, they have a relatively benign side effect profile. With that being said, they still, of course, have some side effects.

So which ones do you need to know for the exam? Let's start, of course, with the black box warning, as you should always know, any black box warning for any medication class. So SSRIs increased the risk of suicidal ideation in children, adolescents, and adults younger than 25 years. This doesn't seem to be the case for older adults, but patients 24 and under need to be aware of this black box warning. Now, this black box warning isn't just for SSRIs in 2004.

The FDA issued this black box warning for all antidepressant drug classes, SSRIs, SNRIs, TCAs, et cetera. So this isn't unique to SSRIs, and I'm not going to bring this up every single med class we go over for the sake of time, but just be aware of this risk with all antidepressants. All right. Next is QT prolongation, specifically sitalopram, most importantly, and then eschatalopram. This is a very important one. When it comes to QT interval prolongation, the biggest culprit by far is Citalopram.

You need to know Cetalabram can cause QT interval prolongation. Eschatalepram, it's a close second. Studies are not as convincing. And then the other SSRIs in the class have minimal to no impact on QT interval. So you need to know these two, especially satalopram. They're going to ask you this at some point on an exam question. So when you see an exam question that asks which SSRI should be avoided in a patient with long QT syndrome, I want you to think of this sentence. If you long for quiet time, you need to escape the city.

If you long for quiet time, you need to escape the city. Long for quiet time helps you remember long QT, quiet time QT, quiet time, long for quiet time, long QT. Escape helps remember eschatalopram, and city helps you remember the most important of all, satalopram. So again, if you long for quiet time, you need to escape the city. That's going to help you remember the SSRI is associated with prolongation of the QT interval, satelopram and eschatelopram. Sexual dysfunction is another one. It's one of the most common adverse effects of SSRIs, actually. It's been estimated that sexual impairment in roughly 50% of patients treated with SSRIs. This occurs in both men and women and includes decreased libido, decreased arousal, delayed orgasm. Sometimes this will get better as the weeks go on if they've been

taking the SSRI for a while. Sometimes you need to decrease the dose to kind of help with this. Sometimes you just need to change the med all together. In some cases, though, the side effects are actually beneficial. For instance, SSRIs are considered first-line treatment for men with premature ejaculation. So sexual dysfunction, another big one you need to know. And then serotonin syndrome, it's a potentially lethal condition that usually results from an interaction between multiple meds that increase serotonergic neurotransmission. It's not specific to SSRIs, as this can be caused by pretty much all the antidepressants will go over today,

all of the serotonergic agents. But SSRIs are one of the more commonly implicated groups of meds leading to serotonin syndrome, probably because their frequency of being prescribed. They're so commonly used. And they're usually associated with a more benign course, though, compared to other classes like MAOIs, which can often be fatal with serotonin syndrome. And we'll talk about more about that later once we get into that class. Next, hyponatremia. So SSRIs are also associated with SIADH and hyponatremia. The risk is pretty low, but you want to be careful prescribing you this is a patient.

patients who are at risk for hyponitremia, your older patients, patients taking diuretics, et cetera. And then finally, we have weight changes. So SSRIs can be associated with weight gain. It's usually not a significant amount of weight, and sometimes it's not clear whether it was caused from the med or the weight gain was just the result of recovery from depression. But it is possible to see some weight gain with the SSRIs. Fluoxetine usually causes the least amount of weight gain, and then peroxitine usually

causes the most weight gain. Remember, the fat parrot to help. your member paroxetine causes the most wake in of the SSRIs. Now there's other adverse drug reactions, nausea, headache, insomnia, bleeding. But for the exam, the ones I went over, those are the ones that are likely to be tested on. So focus on those. All right, next class is our SNRIs, serotonin, norepine reuptake inhibitors. This includes des benelofaxine, deloxetine, level monasopram, milanacepan, and venlofaxine. So there's five meds in this class. But if we're being real for an exam, I just focus on two, deloxetine and venlofaxine. Know those really well, especially deloxetine.

That's likely what you'll be tested on. As far as the mechanism of action, they block presynaptic reuptake of serotonin and norephyrine. So very similar to SSRIs, SNRIs inhibit the reuptake of serotonin, but they also inhibit the reuptake of norephenephrine. They do this by binding to and inhibiting the serotonin and norophenephrenorphins on the serotonergic and noradrenergic neurons. They're also technically weak inhibitors of dopamine reuptake, but the effect is pretty minimal, and I wouldn't worry about that. Main effect is on serotonin and norepi. Now, you probably don't need to know this, but how well these meds affect norepinephrine or serotonin really depends on the drug and the dose. For instance, venlifaxine at low doses is essentially just an SSRI.

It really just affects serotonin, whereas in high doses of venlofaxine, it has really significant effects on norepinephrine. So it's just a little extra knowledge. So again, with SSRIs, we were really just affecting one neurotransmitter serotonin. With SNRIs, we have effects on two, serotonin. So you'll notice a lot of overlap when comparing these two classes. A lot of their indications adverse drug reactions are the same. But there are some differences due to this new interaction with norEPI, which will go over shortly.

So let's talk about the indications next, a lot of overlap like I just talked about with SSRIs. So unipolar major depressive disorder, just like SSRIs, SNRIs are obviously indicated. for treatment of depression. And you might wonder if a class that affects both serotonin and nor epi would be more effective than SSRIs that just affects serotonin. And the answer is technically yes. SNRIs have proven to be a bit more efficacious than SSRIs. But the advantage is fairly small. And with that being said, SSRIs are still usually preferred first line for depression. But SNRIs are a reasonable alternative for initial treatment in certain patient populations, which we'll talk about shortly.

SNRIs are also indicated in generalized anxiety disorder, post-traumatic stress disorder, panic disorder. So there's a lot of similarities when comparing SNRIs to SSRIs. But when things are the same, that's usually not what's going to be tested on. What's usually tested on is the unique aspects. And what makes SNRIs different than SSRIs. And what you should really be familiar with is their ability to treat chronic pain syndromes like diabetic peripheral neuropathy, fibromyalgia, chronic musculoskeletal pain.

So SNRIs possess analgesic qualities that we did not see with the use of SSRIs. And this is likely due to the fact that SNRIs also target nor epi, as we discussed. This neurotransmitter likely plays a role in some form of pain modulation. So this is the main difference to know for indications as the rest are really just a repeat from SSRIs. So SNRIs in addition to treatment of depression, anxiety, etc. also have a dual purpose for treating chronic pain syndromes. So you need to remember that. And the SNRI you really need to know is duloxatine,

because while the other SNRIs have indications for some chronic pain syndromes, duoxetine actually has the largest evidence base to support analgesic efficacy, and it's FDA proof not only for fibromyalgia, chronic lower back pain, osteoarthritis, but diabetic neuropathy as well. So that's the one you really need to know, and that's the one to likely test you on. And the way that you're going to remember that is by, instead of remembering dueloxetine, remember it as dual oxytine, D-U-A-L, dual-oxetine, as it's dual-indicated

for both major depression as well as chronic pain. Then you can also remember dual-oxetine because it's a dual-action agent that has an effect on both serotonin and norepinephrine. All right, adverse drug reactions next. So just like SSRIs, SNRIs are pretty specific, meaning they have little to no effect on your alpha-1 adrenergic receptors, your colonergic, histamine receptors. And because of this, like SSRIs, they have a fairly clean side-effect profile. And their side effects are pretty similar to SSRIs, a lot of overlaps. So I'm not going to waste your time with the similarities. Yes, just like SSRIs, they can cause hyponatremia, nausea, sexual dysfunction, serotonin syndrome, bleeding, same black box warning for increased suicidal ideation

and young adults. What you should really focus on in what's different. So we know this is affecting an additional neurotransmitter nor epi. So this causes new issues we didn't see with SSRIs. The main one to know is hypertension. So this one's unique. SNRIs can cause hypertension, which appears to be due to their effect on noropenephrine. So this is different compared to SSRIs,

and this is the one to focus on. Again, remember, focus on those unique aspects of these classes because there's so much to know. You don't want to waste your time with the overlap. Focus on the stuff that's different. All right, so quick recap, Remember, SnerIs have dual effects. They target not only serotonin but norophenephrin.

Remember, they not only treat depression, but also chronic pain syndromes. Duloxatine is the main one to know, aka dual oxytine. And for ADRs, focus on hypertension. Let's move on to our TCA's next. All right, so tricyclic antidepressants or TCA's. These were developed back in the 1950s, starting with amypramine, and they became first-line treatment for close to 30 years for depression. So why did we stop using them?

well, it wasn't for their lack of efficacy. It's quite the opposite, as they were and still are very effective in treating depression. But the same thing that makes them so effective, being very broad spectrum and interacting with so many neurotransmitter systems, it's also the same thing that makes them so dangerous as they have numerous side effects, and they have a very low threshold for overdose. So due to this, this class of meds has fallen out of favor and has been replaced by newer, safer classes like the SSRIs and SNRIs. they still do have some utilization in certain types of issues, which will go over later, but not so much for depression anymore.

All right. So what meds are in this class? Well, there's two main groups TCAs are broken up into. Your tertiary TCA's, they're known as, which include amatryptylene, clomipramine, doxipine, mypramine, mypramine, trimepramine, and then your secondary TCA's, your secondary amines, which are Dysipramine, nortyphthalene, and protryptylene. So there's a lot of meds in this class, and there's not a good way to memorize. all of them and I strongly suggest against trying to do so you're just going to waste your time.

But if you want to remember one that will likely be tested on, remember amatryptylene. And if you're feeling a bit more ambitious and you want to remember a few of the high-yield meds in this class, just remember you're tripping if you're thinking about prescribing a TCA. You're tripping if you're thinking about prescribing a TCA. So tripping T-R-I-P-N if you're thinking about prescribing a T-CA, trip helps you remember amatryptylene, nor tripdoline, pro, Tripylene and PIN helps remember doxapin. That's all I remember for my exam and it was enough for me to get the question right. So remember you're tripping if you're thinking about prescribing a TCA. All right. So now that we know the meds in this class or at least the important ones, let's talk about how they work next. So TCA's inhibit serotonin and norapinephrine reuptake. So you might be thinking that sounds a whole lot like how SNRIs worked. And you're right. SNRIs inhibited serotonin and noropheny uptake. But the difference is they did this very selective. and very precisely, kind of tiptoed in, did what they needed to as to not disturb other systems in the body,

which is why they had a very clean side effect profile. TCA's, on the other hand, they come in like a wrecking ball, not only affecting the intended targets, serotonin and norEPI, but also affecting the muscarinic receptors, histamine receptors, as well as others, causing a bunch of unintended side effects we did not see with SNARIs. So the difference really is about the selectivity of this class or lack thereof. So indications for TCR, They're not really high yield. I wouldn't waste a whole lot of time here, as many other classes have replaced TCA's as first-line agents. But sometimes these still do come up on exams questions. So let's really quickly run down through some of the indications.

So starting with major depressive disorder, these are not first-line meds or depression. You're not going to use a TCA for depression. This isn't going to be the answer on the test unless they specifically mentioned they have tried and failed multiple other classes, SSRIs, S-NRIs, etc. They may still be called tricyclic an antidepressants, but you're generally not going to use them for depression unless all else fails due to their poor side effect profile. Next, obsessive compulsive disorder, specifically chlomipramine. So clomipramine can be used for the treatment of OCD, but SSRIs are usually going to be, or not usually, they're going to be first line. Chlamyne though is another treatment option only if SSRIs proved to be ineffective. Diabetic neuropathy T-CAs can be used.

Amatryptylene, nortreptylene are some common options. migraine prophylaxis amatryptylene is the only TCA that has proven efficacy for migraines, insufficient data with the other TCA's, nocturnal aneurysus, aka bedwetting, you can use amypromine. It's not first line, desmopressin is, but if the child has tried and failed other treatment options, including desmopressin, amypremine is a second line option. I used to remember I'm a peeing instead of amyprimine to help me remember this indication, but you probably not even be asked about this. And then finally, post-thropetic neuralgia.

usually you start with gabapentin or pregabalin as initial therapy but tcAs are a reasonable second line option i'm sure you notice a trend here these are usually going to be backup options indication for tcas they're not really high yield i don't think you should waste a lot of time memorizing them as in general there's better meds for most of these conditions so where you should be focusing on when it comes to tcas and where the questions will usually come from on the exam is with their adverse effects so tcas like we touched on before they got some side effects and the side effects they get tested on a lot. So let's talk about what you need to know and a little mnemonic to help you remember it. So with TCA's, I want you to focus on that C and TCA's

to help you remember the five C's mnemonic I came up with. So the five C's for adverse effects of TCA's stand for cardiac, cutie, chubby, convulsions, and anticholinergic. So what do these mean? Let's start with the first C standing for cardiac. So all of the TCA's are potentially cardiotoxic. So you want to avoid this class in susceptible individuals with heart disease. TCA's can slow intracardiac conduction, cause various arrhythmias, orthostatic hypotension. And the most important cardiac adverse effect that you need to remember, and it's so important it gets its own C is QD. QD-C-U-T-I should help you remember QT prolongation, QD-Q-Q-T prolongation. So this is a major concern with T-CAs, especially when you mix these

meds with other classes that can prolong the QT interval like certain antimic. microbials, anti-arhythmic drugs. QD helps you remember QT prolongation. Next C stands for chubby. Straightforward, the cyclic to antidepressants block histamine receptors, which can cause increased appetite leading to weight gain. Next C, very important one, convulsions. All of the TCAs can lower seizure threshold. This is dose dependent, so the higher the dose, the greater the chance of a seizure, especially in overdoses. So convulsions, aka seizures. And then the last C, and one of the most important, is for anticholinergic. Dry mouth, urinary retention, confusion, all can start from this. So we touched on this before. TCA's, they're not very selective, and they affect a number of neurotransmitter systems.

One of those is your muscarinic receptors. TCA's block the muscarinic acetylcholine receptors, which causes anticholinergic effects. So these patients may have dry mouth, urinary retention, confusion, blurred vision, tachycardia, etc. So remember, anticholinergic for the last C. All right. So those are your five Cs of TCA's that you need to know. cardiac QD, chubby convulsions, and anticholinergic. If you know those, you should be good for the exam.

Now, one last thing to be aware of is the potential for overdose with TCA's. TCA's have a high potential for overdose, especially when we compare them to SSRIs. For instance, take only takes as little as 10 times the daily dose of a TCA to be fatal. Compare this to an SSRI where it usually takes a really large dose, usually greater than 150 times the daily dose to prove fatal. So in a patient overdoses on a TCA, it can lead to anticholinergic toxicity seizures, but most concerning, it can prolong the QT interval. So you can give them benzos to control the seizures, but the most important therapeutic intervention and the right answer on an exam to treat a TCA overdose is going to be sodium bicarb. Sodium bicarbonate, you need to know this. Sodium bicarbonate is the standard initial therapy for a TCA overdose with hypotension, arrhythmia QT prolongation.

This is the intervention you need to know for TCA overdose. It's what they're going to ask you. So how can you remember this? Well, you remember a tricycle is a small bicycle. A tricycle is a small bicycle. Tricycleic antidepressant. And small bicycle helps remember sodium bicarbonate. Remember, if they ask you, how are you going to treat a TCA overdose?

Remember, sodium bicarbonate, aka a tricycle is a small bicycle. So I wanted to quickly talk about today's sponsor, an amazing tool. for PA students called True Learn. True Learn is a game-changing solution for students preparing for the pants exam or just for some extra help during didactic year. True Learn's test bank offers over 900 test items specifically designed for the pants and 1100 items for the pan read. The questions are mapped to the NCCPA content blueprint, which ensures you focus only on what truly matters for exam day, eliminating the worry of wasting time on irrelevant topics. The questions are created by board certified physician assistants who understand the exam's nuances, and you can

and you can conveniently access TrueLearn's content through their website or their user-friendly mobile app, perfect for studying on the go. You can visit TrueLearn.com to sign up or click the link in the show notes and make sure to use the code, cram the pants when signing up to save 20% off subscriptions of 90 days or more. Now, back to the show. All right, let's move on to the monoamine oxidase inhibitors, the MAOIs. So MAOIs, like TCA's, were one of the first drugs developed to treat depression. We discovered this class really by accident back in the 19.

1950s, they were trying to develop a drug to treat tuberculosis, a drug called iproniazid. And during the study, they found other potential benefits outside of its intended purpose when the patients in the study exhibited improvement in mood. So this med kicked off the MAOI class, and while ipronizate was later removed from the market due to hepatotoxicity, it was replaced by the other meds will go over today. In general, MAOIs, like TCA's, they're rarely used anymore because of their side effect profile, food and drug interactions. and quite simply because we have better and safer options now.

In general, these meds are really only going to be used where nothing else has worked. So the meds in this class are tranolsipermine, isocarbacizid, phenylene, and seledgillin, aka TIPS, because the letters in those medications are TIPS, just a little mnemonic to help you remember the meds in this class. There is another one, mochlobamide, but it's not available here in the U.S., so I wouldn't really worry about that one. So how do these drugs work? while they increase dopaminergic, noradgernergic, and serotonergic neurotransmission by blocking

monoamine oxidase. So I'd understand how these meds work, we first need to understand what monomene oxidase is. So most of the other antidepressants we discussed so far worked by decreasing re-uptake of the neurotransmitters, serotonin, nor epi, et cetera, which in turn left more of them hanging out in the synaptic left to be utilized. But anyway-wise, they work differently. So once serotonin nor epi or dopamine have been reabsorbed by those re-uptake proteins, Some of those neurotransmitters get packaged into vesicles waiting for the next go-round to be released into the synaptic cleft.

But a good portion of those neurotransmitters are actually broken down before they get that opportunity. And they're broken down by an enzyme called monoamine oxidase. And we briefly touch on this at the beginning. Monomene oxidase, it's a mitochondrial enzyme. It's found in the brain as well as a number of other organs. And one of its jobs is to inactivate or break down dopamine, norapenephine or serotonin once they've been pumped back into the presynaptic left. So the more we inhibit monomene oxidase, the more neurotransmitters are available for the next go-round. Now, as another side note, there's actually two different types of monomene-oxidase A and monomene-oxidase B.

They both break down different neurotransmitter. Monomone oxidase A metabolizes more neurotransmitters than monomene oxidase B, and I wouldn't worry too much about that, though. Just know that different meds in the MAOI class can be selective and that they only inhibit one type of monomene, and some are non-selective in which they inhibit both types of. of monomene. So the non-selective agents are isocarboxid, phenylosine, and tranelocypramine. Non-selective, again, meaning they inhibit both M-A-O-A and M-O-B. And then we have seledgillin, which technically can be selective or non-selective, depending on if it's high or low dose. But for the sake of the exam, it's best to just know it as a selective agent. So

seleduline at low doses around 5 to 10 milligrams selectively inhibits only M-A-O-B. And due to this, it's not so effective for treatment of depression, but it can be used in Parkinson's disease due to its effect on dopamine. There's a transdermal patch version of sulegylene that's used for depression, but in general, if you see this med on an exam question, it's usually going to be referred for its use in Parkinson's disease. So I'd really focus on that indication rather than for depression. All right, next let's talk about the indications for MEOIs.

Is there really anything we're still using these meds for? So the short answer is no for the exam and for real life. You're really not going to pick an MAOI. These meds will only be used when all else has failed. And just like in TCA's, it's not that these meds don't work. They actually work very well. They just have two damn many dangerous side effects. So I wouldn't really bother memorizing indications for these meds as it's unlikely to be tested on.

So we'll just really briefly run through the indications. But again, I wouldn't memorize these as it's not usually where you're going to get tested on. So depression, it's not first line. Unit Polar Depression. You can use an MAOI, but only when the patient is unresponsive to several other pharmacos. therapy regimens, different SSRIs, SNRIs, etc. This is not going to be first line. Other indications, refractory cases of panic disorder, social anxiety disorder, bulimia. Key here with all these conditions is, again, that MEOIs are not first line meds, only for

refractory cases. So probably best to just mentally skip the indications for MEOIs, leaving some space in your brain for something more important, such as the highest you'll think to know about MEOIs and what you'll likely get tested on, and that's their adverse effects. So let's talk about that next. So MAOIs can cause blurred vision, constipation, dry mouth, headache, liver enzyme elevation, orthostatic hypotension, insomnia, sexual dysfunction. But that's not what they're going to ask you about. They're going to ask you about the drug-to-drug interactions that can cause serotonin syndrome and the drug-to-food interactions that can cause a hypertensive crisis. That's the juicy stuff you need to know for exams. So let's start with probably the most

important of all, and that is a hypertensive crisis. So if you take an MAOI and eat some cheese, you can have a hypertensive crisis and potentially die. Hopefully it's starting to become a bit more clear why we don't use these meds so much anymore. So let's elaborate on this a bit. So monomine oxidase, as we discussed before, it's not just found in the brain. It's found all over the body, including the lining of the gut wall. And one of its jobs in the GI tract, mainly MEOA, is to break down something called

tiramine. But in a patient taking an M-A-O-I, as we know, this drug inhibits monomone oxidase, meaning tiramine isn't broken down as it should be. So why did this matter? Tiramine in high concentrations can increase norepinephrine release, nor epi can cause vasoconstriction, increased heart rate, and cause a rise in blood pressure, which can precipitate a hypertensive crisis. Long story short, MEOIs combined with foods that have a bunch of tiramine, can cause your BP

to go sky high. So you want to avoid that. Now, what foods have a lot of tiramine in them? The main ones are cheese, meat, poultry, fish, beer, and really any aged or fermented food. If you're a game of Thrones fan, I have a way for you to remember which foods are high in So, tiramine sounds a lot like Tyrion Lannister. And Tyrion, he liked his tiramine rich foods, beer and other alcohol, as well as those

classic medieval foods, cheese meats, fermented, or spoiled food. So if you can't remember which foods are high in tiramine, just think what did Tyrion Lannister eat and drink back in those medieval times, and that's your answer. At least that's how I remembered it. All right, last thing you need to know, these meds can cause serotonin syndrome. So yes, all of the meds we went over today can potentially cause serotonin syndrome. So this isn't unique to MAOIs, but what is unique to MAOIs and why it's often tested on is that episodes of serotonin syndrome involving an MAOI versus other classes are generally more severe and can potentially be fatal. So you really want to be careful with this class of medication.

You never want to mix an MAOI with another serotonergic agent like an SSRI, SNRI, etc. So that's really important. And there are, of course, a lot of side effects for MAOIs, but make sure you really focus on your hypertensive crisis with tiramine-rich foods and serotonin. syndrome, that's likely what we'll be tested on. Okay, so we're almost to the end here. There's three other antidepressants. I want to go over that don't fall into any of the above classes, but they come up very frequently on exam, so let's briefly go over them. So first one is bupropion. So this is a really high-yield meant to know. Bupropion is considered an atypical antidepressant, atypical as the way it works, is distinct from the other classes we have gone over thus far, SSRIs, ascenerize, etc.

What you'll find with these atypicals is they have some unique characteristics, which can make them desirable for certain patient populations. You'll see what I mean in a minute. So how does this medication work? How is it different? Well, bupropion inhibits pre-synaptic re-uptake of dopamine and norepine, which leads to increased levels of these neurotransmitters within the synaptic cleft. Now, how is this different than the other antidepressants we've gone over so far? The main difference you'll notice is bupropion has little to no effect on serotonin. Unlike all of the other classes we have gone over so far, SSRIs, ascenerized TCA's, etc., which did have an impact. on serotonin. Bupropion does not, and its main effect is only on dopamine and nor epi.

All right. So there's a few other high-yield things you need to know for Bupropion, and I recommend committing these to memory because they really like to make exam questions on this drug. So luckily, everything you need to know about bupropion starts with the letter S. At least it does for my mnemonic. So here's the four S's you need to know for this medication, which are seizures, smoking, skinny, and sex. You're very likely going to get a question on one of those, so let's break them down, starting with the first thing. S that stands for seizures. So this is a very important thing to know. Bupropion can cause generalized seizures. The higher the dose, the higher the risk of a seizure. So you want to avoid

using these in patients at risk for seizures. So patients withdrawing from alcohol, benzos, barbiturates, et cetera. And then the highest yield patient populations that's at risk for seizures, at least for the sake of an exam, the one that's always tested on, is a patient with a history of eating disorders. So anorexia, bulimia, they always ask questions on this. You need to know you do not use bupropion in a patient that has a high risk for seizures, especially those patients with eating disorders. You can thank me later when you get this question right on your exam because they always ask it. Next S stands for sex.

So bupropion is the antidepressant of choice if you want to avoid sexual side effects. So if you have a patient who's concerned about sexual side effects is going to start an antidepressant or maybe a patient who's already experiencing sexual side effects from SSRIs, which we know can cause that. Switch them to bupropion. There's even some studies that show benefit from adding bupropion to an SSRI to help mitigate the sexual side effects experience. So you definitely need to know this. It'll likely be tested on.

I used to remember if you add an M to bupropion after the U, it made bumpropion, bump, ropon, bump, rop,on because it's the antidepressant of choice if you want to bump and grind. Next S is smoking, pretty straightforward. Bupropeon is that. is one of the first line pharmacotherapies that can be used to assist with smoking cessation. So another important S for smoking. And then the last S stands for skinny. So bupropion, unlike some other classes, does not generally cause weight gain. In fact, a meta analysis found that on average patients taking bupropion actually lost around

1 kilogram. So if you have a patient who's fearful of weight gain with the other classes, this is another compelling reason to use bupropion as it can cause weight loss. They actually have a weight loss medication called Contrave, which, which is just a combination of bupropion and naltrexone. So if you remember those four S's for Buprion, very likely you'll get the question right. Again, seizure, sex, smoking, and skinny. Next atypical to know is meertazepine.

It's not a lot to know for this one. One major point will go over in a second. So the mechanism of action for myrtazepine, it's kind of complex. There's a lot going on. I don't think you need to know all of the specifics. But the main thing to know is that this drug antagonizes presynaptic alpha-2 adrenergic receptors. That's really important. antagonizes pre-synaptic alpha-2 adrenergic receptors and post-synaptic serotonin 5H2 and serotonin 5-h-3 receptors.

So I'm going to break this down, but for the exam, again, remember, if you can just remember, this drug antagonizes alpha-2 receptors, probably be enough to get the question right, but we'll dive a little deeper for the sake of understanding. Let's first start with the alpha-2 adrenergic receptors. We didn't really talk about these receptors yet because most of the antidepressants didn't work on this specific area. Alas, why this is considered an atypical antidepressant. But alpha-2 adrenergic receptors, they're mainly found in the presynaptic neuron,

and they work primarily through a negative feedback loop. For instance, when nor-epi is released, some of it binds to these alpha-2 receptors, which in turn inhibits further release of noraphenephrine. So this medication blocks these receptors so that negative feedback loop is shut off, and in turn we have more norepine-released, as well as serotonin through an additional pathway. So that's good. In addition, this medication also has an antagonistic effect on post-synaptic, serotonin 5HT2 and serotonin 5 ht3 receptors so it basically blocks certain serotonin receptors which sounds

counterintuitive blocking serotonin receptors but by blocking these two specific receptors redirecting it away from 5H2 and 5HC3 this allows them to bind to a more useful receptor known as the 5HT1a receptor which has a stronger effect on depression this medication also has a high affinity for histamine H1 receptors, which accounts for some of its side effects. Again, this is a complicated mechanism. I don't think it's necessary to know all of this. You probably won't even be asked about this on the exam, but you are likely going to be asked about in the main and possibly the only thing you need to know from mertazepine is that it stimulates appetite and causes weight gain. This is so high yield. I definitely got a question on it. Mertazepine has a big impact on

appetite and could cause significant weight gain up to a 7% increase in body weight. This can be seen in short and long-term use. You need to remember that it's always asked about. So how are you going to remember that? Well, instead of remembering meir-tazepine, I want you to remember it as meal-tazepine, meal-M-E-A-L, meal-tasapine, because remember, this can stimulate appetite, making patients finish their meals and gain weight. One other less important side effect to be aware is sedation. Close to 20% of patients will have drowsiness or sedation, which is likely due to this drug's high affinity for histamine H-1 receptors, but focus on the weight gain as that's the most important thing to know. All right. So last endopressant, we're going to go over is

Trazidone. So Trazidone is in a class of meds called serotonin modulators. There's a few other drugs in this class, nephazadone, velazidone, but tracidone is the one you'll likely get tested on. So Trazidone inhibits presynaptic serotonin reuptake and acts as an antagonist at the 5HT2A and 2C serotonin receptors. So both of these mechanisms we've gone over with other medications. So, Trazidone weakly inhibits pre-synaptic serotonin. So same thing we saw with SSRIs, blocks reuptake of serotonin. So we have more serotonin hanging out in the synaptic cleft to do its thing. And then this drug also blocks serotonin receptors, specifically post-synaptic serotonin

5H2A and 5HT2C receptors. So we talked about this with mertazepine, basically redirecting serotonin away from certain receptors, causing them to bind with more useful ones. Now, trazadone, it's a bit sloppy. and it also affects alpha adreneric receptors and histamine H1 receptors, which causes some high yield, very often tested on side effects you need to know for your exam. This is another drug where the side effects are the most commonly tested on aspect of the drug. So first one is sedation. A study found that 61% of patients taking Traszone experience sedation.

This is likely due to the strong effect this medication has on histamine H1 receptors. So you'll often see this medication being used off label for patients with insomnia. So you need to know this. And the other side effect you need to know a rare but serious one that's often tested on is preepism. So preepism, a persistent erection while rare can happen with this medication. It's a medical emergency. And while it's not common, they love to test on it. And it has to do with the medication's effect on alpha adrenergic receptors.

So you definitely need to know both of these side effects. They're likely going to be on your exam. And the way that you're going to remember them is by instead of remembering trazodone. I want you to instead remember trazabone. trazzo bone so traz with a bunch of disease to help you remember the sedation commonly experienced with this medication and bone to help you remember priapism the boner that just won't quit so those are the two high-ealed things you need to know for this medication and that's what you'll likely be tested on so remember trazabone and you should be good all right so that was your antidepressants it's a lot but stick

to the unique high-yield stuff remember the mnemonics we went over and you'll likely be okay let's do five quick questions to see what you retained question one a sixty-s-sixthes 7-year-old male presents to the office today complaining of persistent low mood, anhydonia, and feelings of hopelessness that have been affecting his daily life for the past several months. Additionally, he reports tingling and burning pain in both of his feet over the past few years and is seeking medication to alleviate this. The patient has a history of type 2 diabetes, hyperlipidemia, and diabetic neuropathy. Its current medications include glomeparide and resuvicatin.

This patient was diagnosed with depression and the decision is made to initiate pharmacotherapy. Which of the following choices would be most appropriate for the patient mentioned above? A, mertazepine, B, Bupropion, C, duloxatine, D, eschatalopramm, or E, fluvoxamine. So that is going to be C, duloxatine. So we have a bunch of different medications that could all potentially treat this patient's depression, but the question also mentions this patient has untreated diabetic neuropathy, evident by the tingling and burning pain in his feet, in which he is also seeking treatment. And there's only one medication listed here that can treat both his depression and neuropathic

pain, and that's deloxetine. Deloxatine, as we know, is an S-NRI. It's often preferred in patients with comorbid depression and chronic pain conditions such as diabetic neuropathy. So remember, instead of duloxateen, remember dual oxytine for the dual indication for both depression and chronic pain, making an inappropriate choice in this patient. Question two, the decision is made to initiate antidepressant therapy and a 28-year-old female with a recent diagnosis of major depressive disorder. Past medical history includes hypertension, hyperlipidemia, and celiac disease. She states her friend found great success with satelopram and was wondering if she could try this medication. Upon reviewing her past medical records, you find a family history of unexplained syncope and sudden cardiac

arrest. What should be ruled out before starting this patient on satalopram? So that is going to be QT prolongation. So satalopram is an SSRI, and one of the biggest concerns with this medication is QT prolongation. You want to avoid this medication in patients with congenital long QT syndrome or any other risk factors for prolonged QT syndrome. So you have a patient with a family history of unexplained syncope, sudden cardiac arrest. This patient definitely needs a workup to ensure she doesn't have congenital long QT syndrome, given her family history. Remember the main SSRIs where QT prolongation is a concern, satalopram first and foremost, and eschatalopram. And if you remember the sentence, if you long for quiet time, you need to escape the city.

You'll never forget the SSRIs that carry the risk for QT prolongation. Long for quiet time, long QT. Escape eschatalopram, city satalopram. Question three. A 32-year-old male with the history of depression has been treated with Certraline for the past six months. He initially showed improvement in his mood, but developed bothersome sexual side effects, including decreased libido and difficulty achieving and maintaining erection. In response to these side effects, you decide to decrease the side effects, you decide to decrease

the SSRI dose, but the sexual side effects persist. Which medication would be most appropriate to replace certraline in this patient? A, satalopram, B, bupropion, C, fluoxetine, D, peroxatine, or E, venlofaxine. So that's B, bupropion. So bupropion, an atypical antidepressant, as we discussed before, does not have the sexual side effects that we see in SSRIs, and it's very commonly the antidepressant of choice for a patient experiencing sexual side. side effects. So remember, bumpropion instead of bupropion, as it's the antidepressant of choice, if you want to bump and grind. All of the other choices are either SSRIs or SNRIs, which all carry the risk of sexual side effects. Question four. A 58-year-old male is spending a night out

with friends celebrating a recent promotion. He is enjoying a few beers, as well as some appetizers of aged cheese, cured meats when he begins to experience headache, nausea, and chest pain. Paramedics recall to the scene, and his blood pressure is reported. it to be 184 over 122. He reports he was recently started on a new medication for his refractory depression, but does not recall the name. Which of the following antidepressants is he most likely taking? A. Certraline, B, mertazepine, C, fluvoxamine, D, phenylene, or E.

Eschatalopram. So that is going to be D. Fenelzine. So we know this is a hypertensive crisis. We know this was caused by an MAOI due to the high amounts of tiramine he consumed, beer, cheese, etc. So what we have to figure out at this point is which one of these is an M-A-O-I. So even if you can't remember the names of all of the M-A-O-I's, which I don't blame you, if you can at least remember the mnemonics tips, T-IPS, you can narrow it down. So we know all of the M-A-O-I's, at least here in the U.S. Start with the letters T-IPS. So that narrows it

down to just two meds in these answers. So you have a 50% chance of getting it right just by using this mnemonic. And if you can remember that certraline is an SSRI from the Serpent Snake-Charmor her pneumotic, you know, all that's left is phenyl zine and M-A-O-I, and that's the correct answer for this question. Final question number five, a 38-year-old female presents to the office to follow up on her recent diagnosis of depression. At the last visit, the decision was made to start psychotherapy, but she finds this to be ineffective and is seeking medication to improve her mood. She's not currently taking any prescription medication, denies a family history of depression, and has no other medical conditions. This will be her first time taking an antidepressant,

and her only concern is the potential for weight gain as she has struggled with her weight in the past. Which medication listed below would be most appropriate to start in this patient? A, isocarboxid, B, doxipin, C, amatryptylene, D, fluoxetine, or E, peroxatine. So that's going to be D fluoxetine. So we have a patient with no medical conditions who's going to start pharmacotherapy for depression. She hasn't tried any meds. We know we start with our first line medications. And we know TCA's and MAOIs are never first-line treatments for depression.

So right off the bat, you can eliminate isocarboxazid and MAOI, and you can eliminate doxapin and amatryptylene, which are TCA's. So what we're left with is fluoxetine and peroxatine. Both of these are SSRIs. So which one is the right answer? Well, technically either one of these would be appropriate to treat her depression, but she mentioned she's concerned about weight gain. And we know peroxitine is the SSRI associated with the most weight gain. Remember our fat parrot. And since this is a concern of hers, fluoxetine would be the most appropriate choice in this patient.

All right, so that is your antidepressants. I hope that was helpful. Thank you so much for listening and good luck in school.