All right, so today we're gonna 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, S, NRIs, TCAs MAOIs, atypical antidepressants.

There's a lot to know here, so I'll keep it as high yield as possible and throwing a bunch of nomonics 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 monoimmine hypothesis.

So the monomine pothesis dates back to the nineteen fifties, basically states that the underlying pathiophysiologic basis of depression is essentially a depletion in levels of serotonin or apenephrine 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 propose mechanism of action.

So before we start with the first class of meds, let's really quickly run down this whole neuro transmitter exchange in the brain.

So we have two neurons close together.

One neuron is the presynaptic neuron, the other is the post synaptic 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 et cetera.

It's stocked with either dopamine, serotonin, neuropinephrin, and they're all stored in these sac 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 left 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 left not really doing much.

Bodies got to 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 not as monoamineoxidase.

A lot of the meds will go over today impact this specific area inhibiting that clean up process.

Some meds block the reabsorption of those neurotransmitters, allowing them to hang out in the synaptic left for longer.

Some meds block monominoxidase, so those neuro transmitters 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.

You get a question and it says, which is the first line med for the psychiatric disorder?

And you can't remember which met it is?

Pick an SSRI and you got to good chance of getting it right.

So the meds in this class are cytalopram esketalaprem, fluoxetine, fluvoxamine, roxetine, and sertraline.

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 SSRISE, 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 anemoonic.

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 gonna 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 charmers sitting down, parad on his shoulder, playing his flute.

The serpent is escaping the basket.

So sitting down should help you remember sit talipram not the same spelling, but same pronunciation.

Parrot should help you remember paroxetine.

And the parad on his shoulder, by the way, is really fat because peroxetine 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 escitelepram m.

Serpent helps you remember certraline.

All right, hopefully that helps remember snake charmer every time you 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 reuptake inhibitor, so SSRIs selectively inhibit the reuptake of serotonin.

So let's start with the words 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.

Select Ativity definitely important.

Now, how do they inhibit the reuptake of serotonin?

Why does this matter?

But we talked about this briefly before.

So SSRIs do this by decreasing the action of that presynaptic reuptake pump, that pre synaptic serotonin reuptake 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 work, 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 reuptake of serotonin leading to increased serotonin levels, they'd be effected 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 serotinergic activity.

And I don't think you need to know this for your exam, but it's believed SSRIs also increase production of neuroprotective proteins that can modify serotonergic receptors, and these added effects, which occur in the week's following initiation of the medication, are thought to be the reason for the delay therapeutic benefit.

So for the exam, remember, these drugs selectively inhibit reuptake of serotonin, leading to increased 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 snrize atypical an adepressants and serotoninodulators that will go over later, they can be reasonable alternatives to ssriz 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, pre menstrual syndrome, and pre menstrual dysphoric disorder, obsessive compulsive disorder, and then blimia nervosa, but specifically fluoxetine, so believe me is another indication for SSRIs.

Specifically fluoxetine though, is what you should remember as it's the only FDA approved med Other SSRIs can be you second line, but the only f first line FDA proved met for bolimia is fluoxetine.

So this is such an easy test question.

I know I got it, and you'll probably be asked this, 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, bolimia has the word bull in it, so a bull is a cow with horns, and then fluoxetine has the word ox in it, and then ox is just another type of caw with horns.

So when you see bulimia, think of an ox as in fluoxetine, the other caw with horns bolimia, fluoxetine, bull and an ox.

The only crappy part about this mneumonic is there's other meds in this class that have the word ox in them, peroxetine, 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 they ask you what's your first line med for bulimia, be thinking of a bowl, 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 cholinergic receptors exception being proxyetine.

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 block box warning for any medication class.

So SSRIs increase the risk of suicidal ideation in children, adolescents, and adults younger than twenty five years.

This doesn't seem to be the case for older adults, but patients twenty four and under need to be aware of this black box warning.

Now, this black box warning isn't just for SSRIs.

In two thousand and four, the FDA issued this black box warning for all antidepressant drug classes SSRIs, SNRIs, TCAs, etc.

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 citalopram most importantly, and then esctalopram.

This is a very important one when it comes to QT interval prolongation.

The biggest culprit by far is citalopram.

You need to know cetalobram can cause QT interval prolongation.

Esctalopram 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 citalopram.

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 payd 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 remember long QT quiet time QT long for quiet time, long QT escape helps remember escitalopram, and city helps you remember the most important of all, citalopram.

So again, if you long for quiet time, you need to escape the city.

That's going to help you remember.

The SSRIs associated with prolongation of the QT interval citalopram and esctelepram.

Sexual dysfunction is another one.

It's one of the most common adverse effects of SSRIs.

Actually, it's been estimated that sexual appairment and roughly fifty percent 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 metal 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 serotenergic 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 to these patients who are at risk for hyponatremia, 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 weightain with the ssrise Fluoxetine usually causes the least amount of weight gain, and then peroxetine usually causes the most weight gain.

Remember the fat parrot to help your remember.

Peroxytine causes the most weake in of the SSRISE.

Now there's other adverse drug reactions nausea, headache, insomnia, bleeding, but for the exam, the ones that 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 nor epinephrine reuptake inhibitors.

This includes ben lefaccine, deuloxetine, level, manaciprim, milnacipran, and ben lefaccine.

So there's five meds in this class, but if we're being real for an exam, I just focus on two, deloxetine and ven lafacxine.

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 nor epinephrin, so very similar to SSRIs.

SNRIZE inhibit the reuptake of serotonin, but they also inhibit the reuptake of norepinephrin.

They do this by binding two and inhibiting the serotonin and norepinephrin transporters on the serotonergic and neuadrienergic 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 nor epi.

Now you probably don't need to know this, but how well these meds affect nor epinephrin or serotonin really depends on the drug and the dose.

For instance, venlofaxine at low doses is essentially just an SSRI It really just affects serotonin, whereas in high doses of ventlefacxine it has really significant effects on norepinephrin.

So it's just a little extra knowledge.

So again, with SSRIs we were really just affecting one neurotransmitter, serotonin.

With s nrize we have effects on two serotonin and norapinephrim.

So you'll notice a lot of overlap when comparing these two classes.

A lot of their indications out of our drug reactions are the same, but there are some differences due to this new interaction with nor epi, which will go over shortly, so let's talk about the indication's next 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, snrize 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 sentrized are 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 similar when comparing snriz 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 s NRIs different than SSRIs, and what we should really be familiar with is their ability to treat chronic pain syndromes like diabetic peripheral neuropathy, fibromyalogia, chronic muscular skeletal pain.

So snriz possess analg sequalities that we did not see with the use of SSRIs, and this is likely due to the fact that SNRI is also target or P.

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 as.

The rest are really just a repeat from SSRIs, so s nrize, in addition to treatment of depression, anxiety, et cetera, also have a dual purpose for treating chronic pain syndromes, so you need to remember that.

And the s NURI you really need to know is douloxetine because while the other SNRIs have indications for some chronic pain syndromes, duloxetine actually has the largest evidence base to support nalgesic efficacy and it's FDA proof not only for fibromyalgia, chronic lower back pain, osteoorithritis, but diabetic neuropathy as well.

So that's the one you really need to know, and that's the one they'll likely test you on the way that you're gonna remember that is by instead of remembering duloxetine, remember it as dual loxetine dul 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, s NRIZ are pretty specific, meaning they have little to no effect on your alpha one adrinergic receptors, your cholinerges, your kissamine 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 gonna 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.

Well, you should really focus on in what's different.

So we know this class 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.

Snriz can cause hypertension, which appears to be due to their effect in neuropinephrin.

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 snrize have dual effects.

They target not only serotonin but norropinephrin.

Remember they not only treat depression but also chronic pain syndromes.

Deloxetine is the main one to know aka dual oxetine.

And for ADR's focus on hypertension.

Let's move on to our TCA's next.

All right, So tricyclic anidepress or TCAs.

These were developed back in the nineteen fifties starting with empromine, and they became first line treatment for close to thirty 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 wore 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?

While there's two main groups.

TCAs are broken up into your tertiary TCAs they're known as, which include amatriptoline, chlomipramine, doccipin, empromine, trimipramine, and then your secondary TCAs, your secondary amens, which are decipromine, nor trip delene, and pro triptlene.

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 gonna waste your time.

But if you want to remember one that will likely be tested on.

Remember Emma trip Delen.

And if you're feeling a bit more ambitious and you want to remember a few of the high old meds in this class, just remember you're tripping if you're thinking about prescribing a TCA.

You're trippin'.

If you're thinking about prescribing a TCA, so trippin' trip space Pin.

If you're thinking about prescribing a TCA, trip helps you remember Amma trip Delene, nor trip Delene, pro trip to line and pin helps remember Doc Sipin.

That's all I remember from 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 TCAs inhibit serotonin and nor epinephrine reuptake.

So you might be thinking that sounds a whole lot like how NRIs worked, and you're right, scent arize inhibited serotonin and orpinephrine reuptake.

But the difference is they did this very selectively 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 scn ARISE.

So the difference really is about the selectivity of this class or lack thereof.

So indications for TCAs 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 exam's questions.

So let's really quickly run down through some of the indications.

So starting with major depressive disorder, these are not first line medser 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, centriize, et cetera.

They may still be called tricyclic anidepressants, but you're generally not going to use them for depression unless all else fails due to their pre side effect profile.

Next obsessive compulsive disorder, specifically clomippromine, so clomippermine 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.

Clomippermine, though, is another treatment option only if SSRIs proved to be ineffective.

Diabetic neuropathy TCAs can be used am atriptlene or triptlene or some common options migraine prophylaxis.

Am Atriptlene is the only TCA that has proven efficacy for migraines insufficient data.

With the other TCAs nocturnal and USIS aka bedwetting, you can use emippromine.

It's not first lined.

Desmopressin is, but if the child has tried and failed other treatment options including desmopressin, mippermine is a second line option.

I used to remember I'm appeeing instead of emipramine to help me remember this indication, but you probably not even can be asked about this.

And then finally, post trapetic neuralgia usually start with gabapentin or per gabbling 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 mets 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 that 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 TCAs, I want you to focus on that C and TCAs to help you remember the five c'snmonic I came up with.

So the five c's for adverse effects of TCAs stand for cardiac, QT, chubby convulsions, and anticholinergic.

So what are these meaning.

Let's start with the first C standing for cardiac, So all of the TCAs are a potentially cardiotoxic so you want to avoid this class in susceptible individuals with heart disease.

TCAs 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 QT QTCUTI should help your member QT prolongation QT QT prolongation.

So this is a major concern with TCAs, especially when you mix these meds with other classes that can prolong the QT interval, like certain antimicrobials anti arrhythmic drugs.

QT helps your member 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 anticholinar dry mouth urinary retention confusion.

All can start from this, so we touched on this before TCAs they're not very selective and they affect a number of neurotransmitter systems.

One of those is your muscarinic receptors.

TCAs block the muscarinic acetylcholine receptors, which causes anticholinergic effects.

So these patients may have dry mouth, urinary retention, confusion, blurred vision, tachycardia, et cetera.

Just remember anticholinergic for the last c all right, So those are your five SE's of TCAs that you need to know, cardiac qt, 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 TCAs.

TCAs have a high potential for overdose, especially when we compare them to SSRIs.

For instance, take only takes as little as ten 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 one hundred and fifty times the daily dose to prove fatal.

So in a PATI 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 arrhythmic 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.

Tricycle helps remember try cyclic and a depressant, and small bicycle helps remember sodium by carbonate number.

If they ask you how you're going to treat a TCA overdose, remember sodium bicarbonate aka a tricycle is a small bicycle.

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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 discover this class really by accident.

Back in the nineteen fifties, 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 ipronyzid was later removed from the market due to hepatotoxicity, it was replaced by the other meds will go over today.

In general, MAOIs like TCAs 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 chrannelcipermine, isocarboxyzid, phenozene, and celegilline aka tips TIPS because the letters in those medications are tips.

Just a little nomonic to help you remember the meds in this class.

There is another one, meklobamide, but it's not available here in the US, so I wouldn't really worry about that one.

So how do these drugs work?

While they increase dopaminergic, ner adrenergic, and serotonergic neurotransmission by blocking monoamine oxidase.

So I understand how these meds work, we first need to understand what monomine oxidase is.

So most of the other endidepressants we discuss so far worked by decreasing reuptake of the neurotransmitters serotonin or epi, et cetera, which in turn left more of them hanging out in the synaptic left to be utilized.

But MAOIs they work differently.

So once serotonin, nor EPI or dopamine have been reabsorbed by those reuptake proteins, some of those neurotransmitters get packaged into vesicles waiting for the next go round to be released into the synaptic left.

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.

Monomine 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, europenephrin or serotonin once they've been pumped back into the pre synaptic left.

So the more we inhibit monomine oxidase, the more neurotransmitters are available for the next go round.

Now is another side note.

There's actually two different types of monomine oxidase, monomine oxidase A and monoamine oxidase B.

They both break down different neurotransmitter.

Mono monomine oxidase A metabolizes more neurotransmitters than monomineoxidase 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 monomine, and some are non selective, in which they inhibit both types of monomine.

So the non selective agents are isocarboxyzid phenozene and chranocipromine non selective again, meaning they inhibit both MAO A and MAO B.

And then we have celegoleine, 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 celegoleine at low doses around five to ten milligrams selectively inhibits only MAOB 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 for version of celegentaline 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 MAOIs.

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 too 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 to polar depression.

You can use an maoi, but only when the patient is unresponsive to several other pharmacotherapy regimens different SSRIs as, centriize, et cetera.

This is not going to be first line.

Other indications refractory cases of panic disorder, social anxiety disorder, bulimia.

Key here with all of these conditions is again that MAOIs are not first line meds only for refractory cases.

So probably best to just mentally skip the indications for MAOIs, leaving some space in your brain for something more important, such as the highest yield thing to know about moois 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.

Monominoxidase, 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 MOOA is to break down something called tiramine.

But in a patient taking in maoi, as we know, this drug inhibits monomine oxidase, meaning tiamine isn't broken down as it should be.

So out of this matter well, tiramine in high concentrations can increase nor epinephrine release.

Nor epic can cause vasoconstriction, increased heart rate, and cause a rise in blood pressure, which can precipitate a hypertensive crisis.

Long story short, MOOI is 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 tiamine in them?

The main ones are cheese, meat, poultry, fish, beer, and really any aged or fermented food.

If you're a gain of thronespan, I have a way for you to remember which foods are high in tiamine.

So tiamine sounds a lot like Tyrian Lanister and Tiian he liked his tiamine rich foods, beer and other alcohol as well as those classic medieval foods cheese, meats for men or spoiled food.

So if you can't remember which foods are high in tiamine, just think what did Tyian Lanister 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 in 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, s centrii, et cetera.

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 will 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 exams, so let's briefly go over them.

So first one is bupropion.

This is a really high yield meant to know.

Bupropeon is considered an atypical antidepressant atypical as the way it works is distinct from the other classes we have gone over thus far, a SSRIs, at centarize, 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's it different?

Well, bupropeon inhibits presynaptic reuptake of dopamine and nor epinephrine, which leads to increased levels of these neurotransmitters within the synaptic left.

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, as, centraized, 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.

So luckily, everything you need to know about bupropion starts with the letter S at least it does formynomonics.

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 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, barbituates, et cetera.

And then the highest deeled 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 the 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 bupropeon 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 bupropeon after the U, it made bump ropeon bump ropeon bump because it's the antidepressant of choice if you want to bump in grind, so remember it as bump ropeon instead of bupropeon to remember antidepressant of choice if you want to bump and grind.

Next S is smoking pretty straightforward.

Bupropeon 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 metal noalo is found that on average, patients taking bupropion actually lost around one kilogram.

So if you have a patient who's fear full of weight game 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 is just a combination of bupropion and nowtrexone.

So if you remember those four s's four bupropion, very likely you'll get the question right again, seizure, sex, smoking, and skinny.

Next atypical to know is mere tazepine.

There's not a lot to know for this one.

One major point will go over in a second.

So the mechanism of action for meretazipine, 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 two adrenergic receptors.

That's really important.

Antagonizes pre synaptic alpha two adreenetic receptors and post synaptics serotonin five H two and serotonin five HT three receptors.

So I'm going to break this down, but for the exam again, remember if you can just remember this drug antagonizes alpha two 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 two adrenergic receptors.

We didn't really talk about these receptors yet because most of the antidepressants didn't work on this specific area.

Last, why this is considered an atypical antidepressant, But alpha two 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 two receptors, which in turn inhibits further release of neropinephrin.

So this medication blocks these receptors so that negative feedback loop is shut off, and in turn we have more nor epinefrin released as well as serotonin through an additional pathway, so that's good.

In addition, this medication also has an antagonistic effect on postsynaptic serotonin five HT two and serotonin five HT three 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 five HT two and five HG three, this allows them to bind to a more useful receptor known as the five HT one a receptor, which has a stronger effect on depression.

This medication also has a high affinity for histamine H one 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, and 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 mertazipine is that it stimulates appetite and causes weight gain.

This is so high yield, I definitely got a question on it.

Martazipine has a big impact on appetite and could cause significant weightain, up to a seven percent 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 mere tazipine, I want you to remember it as meal tazipine, meal meal, meal tazipine.

Because you remember this can stimulate appetite, making patients finish their meals and gain weight.

They're less important side effect to be aware of is sedation.

Close to twenty percent of patients will have drowsiness or sedation, which is likely due to the drugs high affinity for histamine H one receptors.

But focus on the weight gain as that's the most important thing to know, all right.

So last ndepressent we're going to go over as trasidone.

So trasidone is in a class of meds called serotonin modulators.

There's a few other drugs in this class and the fazodone velazidone, but trazodone is the one you'll likely get tested on.

So trasidone inhibits presynaptic serotonin reuptake and acts as an antagonist at the five HT two A and two C serotonin receptors.

So both of these mechanisms we've gone over with other medications.

So trasidone weekly inhibits presynaptic serotonin reuptake, so same thing we saw with SSRIs blocks reuptake up serotonin, so we have more serotonin hanging out in the synaptic left to do its thing.

And then this drug also blocks serotonin receptors, specifically post synaptic serotonin five HT two A and five HT two C receptors.

So We talked about this with mertazipine, basically redirecting serotonin away from certain receptors, causing them to bind with more useful ones.

Now trazodone, it's a bit sloppy and it also affects alpha adrenertic receptors and histamine H one 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 sixty one percent of patients taking traszone experience sedation.

This is likely due to the strong effect this medication has on histamine H one 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 priapism.

So priapism 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 medications effect on alpha adrenergic receptors.

So you definitely need to know both of these side effects.

They're likely going to be on your exist and the way that you're going to remember them is by instead of remembering trazodone, I want you to instead remember trasabone traszebone, so tras with a bunch of dizas to help you remember the sedation commonly experienced with this medication, and bone to help your remember priapism, the boner that just won't quit.

So those are the two high old things you need to know for this medication, and that's why you'll likely be tested on.

Remember trasabone and you should be good.

All right, So that was your antidepressants.

It's a lot, but stick to the unique, high old stuff.

Remember the namonics we went over, and you'll likely be Okay.

Let's do five quick questions to see what you retained.

Question one.

A sixty seven year old male presents the office today complaining of persistent low mood and hedonia 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 patient has a history of type two diabetes, hyperlipidemia, and diabetic neuropathy.

His current medications include glomepera and resove a statin.

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 meritazepine, B bupropion, C duloxetine, D S catalopram or E fluvoxamine.

So that is going to be C duloxetine.

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 duloxetine.

Duloxetine, as we know, is an SNRI.

It's often preferred in patients with comorbid depression and chronic pain conditions such as diabetic neuropathy.

So remember, instead of duloxetine.

Remember dual oxetine for the dual indication for both depression and chronic pain making and an appropriate choice in this patient.

Question two, the decision is made to initiate antidepressant therapy and a twenty eight year old female with a recent diagnosis of major depressive disorder.

Past medical history includes hypertension, hyperlipidemia, and coeliac disease.

She states her friend found great success with cytalopram 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 citalopram.

So that is going to be QT prolongation.

So ctalopram 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 the family history of unexplained syncope sudden cardiac arrest.

Patient definitely needs a work up to ensure she doesn't have congenital long QT syndrome given her family history.

Remember the main ssrise where QT prolongation is a concern cetalopram first and foremost and esctalopram.

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 esketealopram city, cetalopram.

Question three.

A thirty two year old male with the history of depression has been treated with searchulene 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 SSR I dose, but the sexual side effects persist.

Which medication would be most appropriate to replace cetralene in this patient A citalopram, B bupropion, C fluoxetine, D peroxetine or e venlefaccine, So that's B bupropion, so bupropion and atypical antidepressant.

As we discussed before, does not have the sexual side effects that we see in ssrise and is very commonly the antidepressant of choice for a patient experiencing sexual side effects.

So remember bump ropeon instead of bupropeon, as it's the antidepressant of choice if you want to bump and grind.

All the other choices are either ssrise or snrise, which all carry the risk of sexual side effects.

Question four.

A fifty eight 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 age cheese cured meats when he begins to experience headache, nausea, and chest pain.

Paramedics were called to the scene and his blood pressure is reported to be one eight four over one twenty two.

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 certralene, B mertazepine, C fluvoxamine, D phenylzene or E S catalopram, 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 all we have to figure out at this point is which one of these is an maoi.

So even if you can't remember the names of all of the MAOIs, which I don't blame you.

If you can at least remember the mnemonics tips, tips, you can narrow it down so we know all of the MAOIs at least here in the US.

Start with the letters tips, so that narrows it down to just two meds in these answers.

So you have a fifty percent chance of getting it righteous by using this mnemonic And if you can remember that Serchralene is an SSRI from the Serpent Snake Charmer pneumonic, you know all that's left is fenolzine and maoi And that's the correct answer for this question.

Final question number five.

A thirty eight 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 personscryption 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 isocarboxyzid, B doxipin, c amatryptylene, D fluoxetine, or E peroxetine, 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 mets.

We know we start with our first line medications, and we know TCAs and MAOIs are never first line treatments for depression.

So right off the bat, you can eliminate isocarboxyxid and maoi, and you can eliminate doxipin and amatriptlene, which are TCAs.

So what we're left with is fluoxetine and peroxetine.

Both of these are SSRIs.

So which one is the right answer?

Well, technically, either one of these would be a probe to treat her depression.

But she mentioned she's concerned about wekain and we know peroxetine 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.