How Antidepressants Work | STUFF YOU SHOULD KNOW

welcome to stuff you should know a. production of iHeart. [Music]. Radio hey and welcome to the podcast I'm. Josh and there's Chuck and Jerry's here. too well actually that's not true is it. it's a dirty dirty lie what are you. talking about it's just me and Chuck um. we're we're producing our own Jam today. I guess you could say and this is stuff. you should know that's right and uh The. Listener will never hear where we edit.

out when Jerry bursts into the room in 2. minutes we'll just cut that out nice and. clean we should just leave it in once. just to really punish her yeah oh hey. guys. uh she's got like a little bit of miso. in the corner of her mouth oh always a. little crusty miso so Chuck um today we. are doing something in Grand stuff you. should know fashion we're doing a. tangential um.

episode where we haven't done like the. core episode that it relates to have we. never done one on depression officially. I could not believe it I I looked on the. stat sheet maintained by Jill Hurley. which is infallible I looked all over. the. Internet um I sat there and had a. conversation with myself uhuh nothing. it's not. there yeah I mean that's so like us to. hit stuff like bipol first yeah yeah.

yeah we did do bipolar we've done PTSD. we've done ADHD obviously all that but. um we'll definitely do depression at. some point um okay I think it makes. sense maybe to cover this first so how. about that sure Stick it to me yeah put. that in your uh palm and wash it down. with some. water how's that for a Segway oh that. was a good one that was great man so. yeah we're talking about. anti-depressants that was a great one. thanks uh and to talk about.

anti-depressants we really do have to. kind of give at least the briefest. overview of what depression is like um. it's kind of everywhere I saw something. like 60 million adults in America and I. think they um they defin that over age. 18 these days for this kind of stuff MH. have some sort of diagnosed. depression um I think. 20 million of those have major depr Ive.

disorder which also is called clinical. depression or unipolar depression as. opposed to say like bipolar where you. have ups and downs Mania and depression. unipolar is like just oppression yeah. and it apparently is picking up so much. that the World Health Organization is. saying like hey guys by 2030 that will. be the leading disease essentially in. the entire world depression will be um. just the way that things are going and. everyone in the the world I was like.

yeah we know and um it just kind of is. going from there yeah uh I mean that's a. good overview you know without getting. into the weeds as far as numbers go um. symptoms uh as you might imagine. are. um they're sad um disrupted sleep uh. feeling like you're worthless uh. sometimes it affects your concentration. um sometimes it affects your ability to. even experience pleasure at all mhm uh.

even you know when you're you know doing. something that might ordinarily be fun. for you it's not fun um it's not uh. being sad in a moment or being blue for. a little while um it is a persistent. thing where it disrupts your life it. interferes with your life it can. interfere with your relationships and. interfere with your relationship with. yourself in a big big way yeah and um. for a lot of people I think for most. people statistically speaking it's.

chronic or recurring um you don't just. have one episode it can keep coming back. and and back um and it's nothing new. like depression is not new although it. does it has really kind of picked up as. far as diagnoses and prescriptions go. but I mean we used to call it Melancholy. and they Associated it with black bile. all the way back to. hypocrates um and depending on what. culture you were from they would either. say um tell you that you needed positive.

rewards if say you lived in Persia in. the 9th century or if you were in. medieval Europe they would might burn. you at the stake or something like that. luckily we've come a long way with. treating depression that's the that's I. think we should say here at the outset. that's the message we're trying to say. like it is highly treatable yeah like if. you have depression and you you're not. treating it there's definitely hope so. please don't feel like there's not there. there's plenty of Hope and if anything.

hopefully that's what we get across this. in this episode um but there used to be. they used to give people enemas they. used to give people baths um positive. thinking diet exercise and what's. interesting Chuck is some of those are. still prescribed today depending on the. severity of your. depression yeah for sure and those. things very much help and I'm glad you. said that what you said just a second. ago because when I said uh I sounded. very very down when I said said that the.

symptoms are and I paused and just said. sad um there is a lot of Hope but it you. know I have everybody you know has if. they don't suffer from the depression. you have people in your life and your. family and your friends that do and it. and it makes me very sad because these. are you know great people who have uh a. hill they need to consistently hike up. and I imagine it uh it is something that. drains your life force uh and we here to.

talk about some of the ways that you can. change that yeah um just as an aside. every time I think of depression being. like really accurately portrayed I think. of um Kirsten Dunst in Melancholia the. large von Trier movie yeah large vontre. of all people seems to have most. accurately portrayed clinical depression. great movie in that movie it is a great. movie but she just does an amazing job. um like there's a part where she's just. in physical pain such physical pain from.

being so depressed that like she can. barely crawl into a bath it's really. it's hard to watch that was a one-time. for me yeah uh not the kind of movie you. watch over and over but l b LS voner can. make a great great flick and I love. Kirsten D she's great for sure um so we. should say that you rarely will get an. enema when you present yourself to a. physician um and are diagnosed with um. Clinic depression major depressive.

disorder instead um they will prescribe. you pills anti-depressants and the. reason that they will prescribe you any. depressants is because ever since the. 70s people have kind of basically um. treated depression based on What's. called the biological model and the. biological model says that you're. depressed because there's an imbalance. of neurotransmitters chemicals in your. brain and usually they zero in on. serotonin they say you are depressed.

because you have low levels of Serotonin. and that's been the the dominant view um. for decades now that's how we treat. depression is based on that presumption. yeah and it's it's accepted and it's not. like it's accepted with you know through. gritted teeth uh I think most people. agree that's uh what what most people. agree on is they don't really understand. what might be the underlying issue or. the mechanism behind that is um we do. know like a lot of the things that may. uh lead to depression uh if you're uh a.

woman you're more likely to get uh what. you call it MDD yeah major depressive. disorder yeah major depressive disorder. um if you have suffered a loss or. unresolved grief and these are things. that can compound it's not like again. that's different than being sad about. you know losing a loved one or something. like that um but it can help contribute. to MDD same as if you suffer uh through. a stress early in your life that can all. contribute so we know some of those.

things but we don't know that underlying. mechanism that actually causes it and. because that we don't exactly know how. anti-depressants work uh we know that. they do work and we know what they do. but if you really don't know the. underlying cause you can't just say like. yeah we have anti-depressants completely. figured out because we know they work. and we know how they function yeah so. much so we have so little of a grasp on. how people become depressed especially. like like MDD depressed um that studies.

show that people with MDD don't have. aren't likelier to have lower levels of. Serotonin than other people uh like and. that just throws out basically the whole. premise of the biological model and yet. we know that anti-depressants work they. work better than Placebo they're. definitely doing something and we know. that by Design what they're doing is. going in and messing with the. concentration of neurotransmitters in.

your brain so we know they're doing that. we just don't know how that mechanism is. treating the depression we just know it. works and I guess over the years um. psychologists or psychiatrists and and. doctors have been like let's just not. ask. questions uh well thankfully we know. that's not 100% true because they are. still studying and trying to figure this. out uh there was a study that uh I guess. you dug this one up from last year.

uh from the University of Colorado go. Buffalo's um that hypothesized that um. increasing well increasing serotonin we. know that alleviates symptoms but it's. not like uh it's just rebalancing your. brain and and picking up um a level that. you had that was low uh they are saying. from the study that maybe it's helping. to repair the neuroplasticity in the. brain and just sort of like uh their. brain circuit it become just sort of.

stuck and lodged in that depressed state. and it helps to unstick those yeah. that's a new wish from what I can tell. rival Theory to the biological model um. even though it's biological itself it's. very very confusing stuff but um the. idea remember you said earlier that like. you differentiate you know um MDD or. even just non major depression but you. know diagnosable depression from from. just a passing.

um feeling of the Blues right for like a. day or so yeah or mood swings you might. call it whatever sure so um this Theory. basically says that thing that people. normally come out of people get stuck. and it just seems to get worse and worse. and worse the longer you're stuck in it. or the the the harder you're stuck in it. so um that's a I I love that theory and. there's actually support for it because. some of the newer more uh far out. treatment ments psychedelics in.

particular like ketamine and psilocybin. MH they have been basically irrefutably. shown to treat major depressive disorder. really well and we know that psilocybin. for example goes in and basically. rewires your brain so that that would. support the idea that it's a change in. neuroplasticity that anti-depressants um. create that helps treat depression yeah. for sure uh and we also know you know. you mentioned serotonin and. norepinephrine and and you know messing.

or balancing out the brain chemistry mhm. uh what's what's literally going on and. what they're designed to do. anti-depressants that is and we're going. to talk about I guess all of them. probably right by God we. are uh they interfere with What's called. the synaptic transmission of these. things of serotonin norepinephrine. dopamine uh and that transmission is is. the movement of neurotransmitters from. one neuron to another they're they're. they're leaping from one to another.

they're talking to each other they're. getting to know one another and it's. that transmission that uh we know is. what anti-depressants affect right. that's where the money is they go to the. the horse's mouth that's another word. for the synapse that's what neurologists. call it the horse's mouth that's right. with the ultimate goal for all of these. to increase levels of uh of those things. um usually uh I mean some nor. epinephrine as as you'll see as we talk.

about but more along the lines of. Serotonin right here's the twist to all. that though neurotransmitters do all. sorts of other things besides say like. regulate your mood um I think serotonin. does all sorts of crazy stuff like um it. helps regulate sleep digestion nausea. blood clotting bone growth it does. everything right so if you start messing. with the serotonin in your brain it can. also start to mess with the other.

functions that serotonin uh does hence. side effects so those are something that. we are still figuring out too but. luckily that's another thing we're. getting a handle on is the side effects. uh that feels like a good break point. that's a a big old table setting yeah. yeah yeah we've got a dessert knife and. a butter knife I don't know which is. which pal can you help me out the. dessert knife is a little smaller. fancier it's got a kind of a sharp. pointy end that you could easily drive.

through the hand of the person sitting. next to you at the table well no I mean. when I reach for the wrong one just just. give my hand a little smack I'll drive. my dessert knife through your hand how. about Perfect all right well we'll be. right back and start off with the star. of the show The SSRI. [Music].

[Applause]. [Music]. all right so we promised to start off. with ssris and we're starting off with. that we're kind of gonna jump around. starting with the most frequently.

prescribed sort of modern version of. anti-depressants and then we'll jump. back in time uh and talk about drugs. that you know maybe your parents took. who knows uh but these came around in. the mid 1980s I think the very first one. to became uh to become available was uh. fluoxitine in 1988 mhm um and we're. going to I guess we'll say both their uh. regular name and their trade name or.

trademark name just so everyone knows. kind of what we're talking about yeah so. the people who take them can like be. like yeah yeah. EXA uh fluoxitine is is Prozac uh. perotin is. paxel uh caline is Zoloft uh. fluvoxamine is louo MH uh these are a. challenge for me you're doing great man. I appreciate it. uh satala pram is Celexa. and why don't you take that Lex Lexapro.

for me what is that uh escalo pram. escalo pram oh okay I just had a little. Es at the beginning of that you did. fantastic my favorite out of all of them. is. fluvoxamine yeah that's a good word I. just like I like all those letters. together like that it's great yeah and. I'm not saying the drug itself just the. word yeah so these are the ssris um that. are going to block they're called. reuptake Inhibitors and what that means. is they're going to block that that bust. trip that serotonin takes back to that.

original cell the pre synaptic cell M. the one who sent that. transmission uh and it leaves it. floating around in that space in between. uh I believe that's probably you that. said that's where all the action happens. yes but that's in the What's called the. synaptic Clift so it sends that that. serotonin out and when it comes back. instead of uptaking it or re oftaking it. it blocks that from happening so that. just means there there's more of it. where you need it there just hanging out. there like where's my Uber yeah.

exactly so uh that was lame I'm sorry. everybody um pretty good it's like it's. an Uber share there is so many other. things I could have said and I just I. don't know I couldn't come up with. anything better you're trying to wedge. in jokes in a unfunny episode okay thank. you for that that's what we try and do. wedge in jokes where they're not. appropriate so that's what that's. specifically what you just said SSRI is. to and they live up to their name.

essentially yeah I don't think I even. read out what it stands for Selective. serotonin reuptake inhibitor or it may. have but there it is I thought I think. you did but yes so they specifically. focus on serotonin and they prevent its. re-uptake from the the synapse that sent. it or the um the neuron that sent it out. right um so the great thing about ssris. is that they work really really really. well on most people with the fewest side. effect um and it's in part because they.

selectively Target serotonin and despite. the fact that there's fewer side effects. and fewer people than other types of. anti-depressants some people do not. respond particularly well to it um it. depends on the brand not necessarily the. brand but the type of drug I mean all of. the ssris aren't exactly the same so if. one's not working for you you can try. another one and another one and another. one and if that doesn't work then you. might move on to another class of.

anti-depressants but uh from what I can. tell ssris are essentially still today. like basically the um the flagship. anti-depressant if there is such a thing. yeah I think you're right and I think. that uh when it comes to getting that um. if you're on more than one either that. that cocktail right or that single SSRI. correct uh that is where your doctor. comes into play but that even though. I've never been through this I've been. know plenty of people who have I I.

believe it's safe to say that's also. where you come into play though as. advocating for your for yourself in in. uh concert with your doctor right for. sure is that a good way to say that it. is and patient education is a really. important part of um treating depression. like it's not one of those things where. you just turn up and say what you know. here treat me like you're going to be. armed with a lot of stuff on how to help. yourself too and I guarantee you they're. going to say exercise every day for 20.

30 minutes a day will be one of the. things that they say because it works so. well it's crazy what it does and that's. that's part of also treating things with. anti-depressants is if you are um. suffering from major depressive disorder. you probably can't get yourself up and. exercise right so on anti-depressants. you are you the it increases the chances. that you can exercise and then that just. makes it uh even more effective. yeah I uh if you suffer from depression.

and you feel a little lost um and you. are a a fan of Comedy um I can highly. highly recommend the uh great comedian. Gary Gman um he's a comedian who has. he's been around a long long time and. it's not like that's his act but he did. have one tour and one sort of set where. he really really dug into this and one. special uh and then lately uh he wrote. about it in his book which is great I. read the book uh this is all about his. childhood growing up but lately on. Instagram he has been um posting just.

daily things he's kind of written down. on a paper that helped him when he was. at his darkest and you know take a walk. things like that but but drilled down. and got more specific and um advice on. if you're a friend of someone like what. you can do like it it's really really. really helpful so Gary Goldman's awesome. and I encourage you to check out that. Instagram as silly as that sounds um it. can really help it doesn't sound silly. at all well anytime you're like oh go to. a social media thing and look at what.

this comedian said but you know what I. mean uh no I still don't think it was. silly I think it was a great shout out. for sure good um so a couple more things. real quick on ssris before we move on um. they are they have fluoxitine in. particular Prozac has a long um halflife. yeah so you can get away with just one. dose which you're like who cares one a. day yeah but that um actually decreases. your chances of missing a dose so that's. a good thing and then one of the other. things too is when you go to the doctor.

especially if you're a kid they start. treating you with anti-depressants. they're going to start out really really. low dose and just kind of slowly move it. up and as you get adjusted to it it cuts. down on the chances of side effects but. there can be side effects with SSR from. anxiety to sexual dysfunction to vertigo. um so I mean you you need to go into it. understanding what you're facing but a. good psychiatrist or doctor will be like. okay let's just do this a little at a. time. to get you on your feet as as gently as.

possible yeah for sure all right so. that's a quick overview of the ssris and. how they work now we're going to move on. to we're going to jump back in time oh. we get in the Wayback machine that's fun. oh okay let's do. it uh to the 1950s and 60s when uh. tricyclic anti-depressants made their. debut. um yes those were some of the first but.

not the first strangely um but these. were really kind of early pioneering um. anti-depressants that they worked on. serotonin that was kind of their goal um. they were a re-uptake inhibitor as well. the problem with these things are is. that they um weren't selective that's. that's why ssris are just so desirable. tricyclic anti-depressant they just like.

come here a neurotransmitter and they. kind of dry hump the neurotransmitter no. matter what kind of neurotransmitter it. is and prevent it from being taken back. up again all right that's one way to put. it uh all right we're going to name. these and these again might be things. you saw if you're a a gen xer you might. have seen them in your in your. grandparents uh medicine cabinet even. yeah you probably associate these names. with the smell of moth balls that's. right. exactly uh let me see here here's the.

first one nor. norri nortryptiline. naline these are no ssris jeez I even. practice these nortryptiline why am I. getting all these that's Pamelor how. about you take the next one I I can't. yeah sure you can uh. Molene that's L the the brand name's. even worse Ludo Mill yeah uh deseine. that's nor Prine is the brand name name. uh amitryptiline good job yeah.

chamine that does not roll off the. tongue that's anril and then. imipramine which is trenel I've never. heard of any of these um but they. apparently work fairly well it's just. the side effects that are really. problematic I mean strangely they treat. it just as well as ssris but again they. treat everything all the. neurotransmitters and because as we've.

seen neurotransmitters perform more than. one function in the body um they have a. whole host of side effects that you just. don't want yeah I mean yeah we could go. through them but it sounds like one of. those commercials uh but you're way more. likely to experience those with those. than the. ssris uh it's also they were uh the. tricyclic were easy EAS easier to. overdose on yeah uh and you're just not. going to see them a lot for depression. these days they're they're still around. I think neuropathic pain is something.

they found use for yeah uh and if you. you know if you don't tolerate SSR eyes. they might say you know they might pit. you a drug from the 1950s right that has. for I saw a blackbox warning that the. FDA slapped on it that says wow really. can cause suicide uh and I was like how. how does that stuff happen and um the. the way that I saw it explained is that. um if you have have like if you are um.

if you're suicidal and you have. depression you're thinking of suicide. you may be too immobilized to actually. carry it out uhhuh a tricyclic um anti. depressant May lift the depression just. enough for you to act and apparently. they they they there's a warning on the. box that says that um so yeah tricyclics. don't sound particularly desirable yeah. but they probably saved quite a few. people in the 50s and 60s when they came.

out yeah for sure I mean that was a long. time ago so this was early sort of you. know medicine at work yes um we have. snri. serotonin uh not just serotonin but. serotonin and norepinephrine reuptake. Inhibitors M uh they came around in the. mid 90s so after the SSRI is a little. bit after and they do exactly what you. would think they block the reuptake of. both of those uh in the same way uh yeah. and what's weird is SN eyes you think. it's better right yeah despite.

selectively targeting two. neurotransmitters it's basically just as. good as the. ssris yeah I think they have about the. same number of side effects too yeah and. those are uh there's only a couple of. those um effexor and. syala in calta's case that's. duotine and effector is uh. venlafaxine not not the best name ever. Ben LAX scene Ben Affleck scene that's.

right what just happened that was great. man Ben affle scene is dunan yeah you're. right there's another related class. called noradrenergic and specific serot. serotonergic I'll bet the psychiatrists. are just laughing laughing laughing have. fun fellas or else they turned this off. a long time ago yeah but those type of. anti-depressants. nsas uh lowercase a first so I'm pretty. sure there's no other I guess you could.

say n. ssas surely people don't say that nasas. sure that's even better it's better than. ven. Laine yeah yeah they came around in the. what mid 80s yeah um they the the. nassas have they do the same thing but. they have different side effects it's. just so bizarre yeah um like you can. experience weight gain and sedation. rather than say sexual dysfunction like. on a um snri but it they're all doing.

the same thing but again none of them. seem to be any better than ssris and. ssris have the fewest side effects this. episode is brought to you by ssris by. the. way uh the next thing we're going to. talk about are M aois or uh monoamine is. that right monoamines monoamine uh. oxidase Inhibitors you got all fancy and. I yeah I don't think we've mentioned yet. that that's what that group is called. serotonin norepinephrine and dopamine.

are all monoamines MH uh because of the. molecular structure of those things yes. so I've heard of maois like basically my. whole life haven't you uh no oh okay so. they're this like very like widespread. class of drugs but they have a weird. twist to them in that they um prevent. you from breaking down something called. tyramine which is an amino acid. and tyramine is great because it.

regulates blood pressure but you don't. want too much tyramine it gets out of. whack and your blood pressure gets out. of whack and tyramine is present in a. lot of different foods from like soy. sauce to fish to sausage age cheese the. best cheese yeah um and as a matter of. fact it's called the cheese reaction. where people get hyper hypertensive from. taking maois and accidentally eating the. wrong food so what the mono amans get. broken down by is monoamine oxidase.

Mao and MAOI is a monoamine oxidase. inhibitor that's right so it prevents. this thing from breaking down the. monoamines and that's why you can't eat. age cheese do you think anyone ever goes. in and they're like can I just do the. ssris because everyone kind of knows. those. right uh should we name check. those um I've never heard of any them. but sure if you want no I don't feel the.

need to well I think what's also. interesting is that it was discovered by. accident uh oh yeah that's right this is. one where um I think it was in the early. 1950s they were testing U drugs for TB. for tuberculosis MH and it was one of. those deals where they said hey um these. people over here taking this thing. they're sleeping pretty good they have a. a good appetite they're they're bouncing. around the room they seem pretty happy. um and so that that's how it was born. they found that I think that uh when.

they gave it to patients with depression. that 70% of them showed an improvement. so they said I guess we've got a new. thing here yeah so I think they started. in 1958 with Marcel the first ever MAOI. anti-depressant but again because you. can't eat age cheese people don't. usually prescribe that as an. anti-depressant anymore got to had that. cheese doc sure I mean yeah that'll make. any way depressed not being able to eat. age cheese uh I guess now we can uh jump.

over to or should we take a break or. should we cover uh neutral I think it's. I think it's break time all right we'll. take a break and then we'll come back. and talk about um something that you can. just get over the counter it's called a. neutraceutical right after this. [Music].

[Applause]. [Music]. okay Chuck so we started to talk about. neutraceutical and that's just a fancy. name for a supplement that you could. conceivably use to treat a malady and in.

this case uh people have long been. seeking supplements to treat depression. with uh whether it's clinical or you. know diagnosable or passing depression. who knows people don't necessarily want. to take Pharmaceuticals and it's tough. to blame them so they'll follow studies. and they will read about new discoveries. with people poking around trying to. figure out what causes depression and. very often they'll turn up some specific.

amino acid or something like that that. they show that there's low levels of. that in the brain of people with. depression and so they'll go off and. test this amino acid and they'll show. like yep actually it improves symptoms. and then people go out and buy tons of. that supplement but the problem is in. the United States if it's a supplement. it's essentially totally unregulated so. there's no one checking out like to make. sure that the dose is the same pill to. pill that there actually have what they. say they have in them that they don't.

have um old newspapers ground up with it. like it's just the wild west when it. comes to supplements which makes it. really a tricky thing to treat your. depression with even though I I totally. understand how somebody would not want. to take Pharmaceuticals if they don't. have to yeah for sure and uh you know. this is a real shame because a lot of. these studies on these uh have come back. with some some results that are that. look pretty good um some of them show. you know can kind of be over the all. over the place again maybe because it's.

not regulated is the reason because some. studies show that uh results can can. treat MDD pretty effectively others show. it's not any better than a placebo MH um. they can also have side effects so it's. not like oh it's just a supplement so I. don't you know I don't hear the. commercial listing you know a laundry. list of things that could go wrong then. and I can buy it uh just over the. counter then there can't be any side. effects right but that's not true at all. there are side effects the supplements. as well and it can you know there have.

been plenty of situations where uh. there's a supplement that becomes kind. of the the all the rage yeah um and. people just start like uh St John's wart. used to be when people were just like. hey St John's W's the best we just. should take tons of it and that can. result in its own set of issues I. remember that that was our parents. taking St John's wart wasn't it uh yeah. I. remember my parents even at one point. signed up for one of the uh supplement.

uh you know pyramid schemes I guess it. was no really sort of like the Avon. Laney but it's supplements I remember a. short time I mean they were always. trying to hustle some side gig because. they were teachers but um I specifically. remember when I was a kid that we just. had like a house full of this stuff for. a while and I can't remember which. system or brand this was but if someone. wrote in and told me I would be like oh. yep that's the one yeah I I can't bring. it to mind either but I'll bet I I know.

what you're talking about yeah um so. yeah St John's wart it was all the rage. in the 80s and I think one of the other. things that lent it a lot of credibility. is people have been using St John's wart. to improve mood for probably thousands. and thousands of years if not longer. yeah the problem is is all that time. through history people weren't also. taking like birth control pills or. pharmaceutical anti-depressants both of. which St John's wart reduces the effect. effess of you don't really want to.

reduce the effectiveness of your birth. control pills if you're trying not to. get pregnant at that time uh it also. breaks down it also prevents the. breakdown of antihistamines it does all. sorts of unwanted stuff and that's just. such a great like Stellar lesson in the. problems with using a supplement to. treat something like major depressive. disorder but it's also a lesson in just. how far we need to go to look into. non-pharmaceutical treatments for stuff. and actually study them and figure out.

exactly how to do it and start producing. that treatment as well um because I you. know I think most people do prefer. something that you could conceivably. consider more natural than a. pharmaceutical no for sure the problem. with that though is is that it's we're. not set up the United States at least. isn't set up to make a trillion dollars. off of St John's wart it's tough to do. that that as opposed to creating a new. proprietary compound that that treats.

depression yeah for sure uh so I mean. that leads very nicely into psychedelics. uh we promised talk of those earlier. with ketamine and psilocybin and here we. are uh they um at least for for ketamine. that is one that is um way out in front. of psilocybin as far as like official. studies in the government kind of. getting behind some of this stuff yeah. they love K yeah they love that K. they're being tested um ketam that is as. a breakthrough treatment and. breakthrough is a label or a designation.

rather that the FDA says hey um we can. FastTrack this through the approval. process because we think it has so much. potential um and these still though even. though like ketamine has shown a lot of. Promise it's still looked at and studied. as a last resort if you're resistant to. other more traditional treatments yeah. so the government was all about I should. say the FDA um back in. 2019 they prescribed or they approved. sorry sorry a a prescription version of. ketamine called.

esketamine and apparently that to. ketamine I've seen compared to CBD to. THC right there were a couple double. colons in there if you didn't that up a. water down version exactly that like say. a geriatric person might take yeah. exactly um they started to develop uh. ketamine in the. 1960s uh in Belgium and um you know. they've been like you said I think uh. starting in 2000 um is when they really.

started kind of looking into stuff so it. had a big jump on psilocybin um that's. one that's just now starting to kind of. uh people are starting to say Hey you. know you know magic mushrooms I know has. a has a a bad connotation for a lot of. people so let's call it psilocybin you. know the medical or you know the I guess. biological name uhuh and let's let's. study this stuff yeah so psilocybin is. just gang ERS at treating depression. ketamine is too we should say also that.

psychiatrists are like we need a more. potent version of ketamine so please. approve that FDA right uh they're not as. far as I know uh on the way to do that. but who knows um but siloc cybin in. particular um there's just study after. study after study that's like this stuff. really works and it works in like you. don't have to stay on it you don't have. to take mushrooms every day for the rest. of your your life which you know but you.

only take them a couple of times and it. can have effects that last up to a year. there was a I think a John's Hopkins. study from. 2022 where they gave two doses of. psilocybin to patients two weeks apart. uhhuh and um so they gave each patient a. dose of psilocybin two weeks apart they. didn't just wait two weeks to go to the. next patient I guess is what I'm saying. yeah so they found that this the effects. could last like a year after a year from. the second dose um they they and that.

the effects were like just mindblowing. too as far as the the I guess. quantifying the symptoms of depression. right yeah do you know how what uh what. the dose was before I give this number. um I think it was like melt your face. half a bag right two handfuls I'm very. curious but um this is uh I think it was. depression rating scale they were using. where 24 was severe and seven or below.

was no depression and before they had. the psilocybin they scored 22 an average. of 22.8 out of 24 as far as being. severely depressed uh and then afterward. it went all the way down to 7.7 which is. just a sco above no depression yeah and. that 7.7 was that followup a year later. yeah that's remarkable yeah so that was. 2020 2 I wonder if they check in with. these people now what the scores will be.

you know ises it do you have to take. psilocybin every two years twice over. two weeks and maintain control over. depression that's it's pretty amazing um. there's another study from 2024 that. found that psilocybin um is at least as. effective at treating um MDD as ssris. probably more yeah and I think they had. did try to follow up with those people. people but they got no self-service out. there in Joshua Tree that's.

right so just real quick there's um we. we because we'll probably go over this a. little bit in the depression episode but. if you go in for treatment of depression. they're going to treat you in three. different phases two possibly but. probably three the first is acute where. you show up and you're like I can't take. this anymore I need treatment they're. going to get you on SSR or yeah probably. an SSRI but they're going to get on some. anti-depressant to start they're going.

to try to work their way up while also. balancing getting you feeling better as. soon as possible and time was they would. um try an anti-depressant for like four. to six weeks that was the what was. generally prescribed like that's what. all psychiatrists did and if after four. to 6 weeks there wasn't more than a 25%. reduction in symptoms they would say. this isn't working for you let's try. another one but I guess something. happened to the psychi Zeitgeist and now. they're waiting as long as 6 months to.

give it a chance um which has got to be. tough when you're suffering from major. depressive disorder but that's the acute. phase and once they get a once they find. an anti-depressant that can manage your. symptoms you'll move into What's called. the uh continuation phase that's right. and that's um after remission has begun. and that is when they're trying to uh. you know knock down or or out eliminate. uh the symptoms that are still sticking.

around and get you back to where you. were before your MDD episode um after. six months of that if there's no relapse. then uh they may wean you down or. completely off of something um it you. know it just sort of depends like again. like talk talk a lot to your doctor. through all this stuff so you really. have a good handling what what's going. on so I think I said most people will. suffer multipolar chronic or recurring.

episodes of major depressive disorder. once they have one yeah something like. 50 to 85% of people who have one will. have another episode um so there's it's. probable that your continuation phase. will eventually turn into a maintenance. phase where they'll just keep an eye on. you you'll probably keep up with say. therapy or psychoanalysis or something. like that um and if your episode starts. to come come back they'll put you on the. anti-depressant that worked before yeah.

and this can go anywhere from a year to. indefinite mhm just the point is to stay. on top of your symptoms so that you. don't have another episode or if one. starts to come along they nipp it in the. bud very quickly yeah for sure um which. kind of all leads to the question are. are these being prescribed too much. that's you know you can't hardly bring. this up without hearing somebody say. yeah they're just doctors are just. willy-nilly prescribed this stuff to. everybody like young children all the. way to senior citizens like they'll just.

throw anyone on that and that's just a. very sort of dumb down way to look at. this uh there are critics who you know. have valid points about stuff but you. have to look at real numbers um as far. as like an increase in prescriptions um. if if you look at the numbers part of it. is that they are uh they are staying on. something for longer so if if they're. keeping you on something for six months. rather than just switching something out. at six weeks then the numbers for that.

prescription are going to be higher over. a six-month period so there's just a lot. more Nuance in those uh numbers as far. as there's been a big increase like a. sweeping statement like there's been a. big increase in the number of. prescriptions right plus if you're just. counting prescriptions of. anti-depressants you might miss that say. the tricyclic anti-depressants are now. being prescribed for neuropathic pain. right so that would get lumped into that. as well and yet you can totally get the. Viewpoint of people who are like yeah.

that probably accounts for some of it. but dude um I saw a statistic that in. the United States um people ages 12 to. 25 uh between 2016 and 2022 monthly. prescriptions of anti-depressants went. up. 66% yeah I mean 2016 to 2022 is also a. period of a lot of upheaval in the. United States and with and starting in. 2020 with co uh around the world so uh. all all of that stuff comes into play.

for sure yeah I think from 2020 to 2022. if you just look in that window. especially for I think girls and women. aged 12 to 25 it went up like. 150% in those two years kids pulled out. of school in their entire social. structure sometimes yep yeah yeah so um. it's also possible that that the stigma. has been reduced thank you Jen Z around. seeking treatment for mental health and.

talking about your mental health so more. people could be seeking help which could. lead to a higher increase in diagnosis. which would of course lead to an. increase in prescriptions at the same. time some people are like we're just it. a lot of this is just pathologizing. human sadness and we need to especially. so everybody agrees basically that if. you have a low level diagnosable. depression that's not MDD mhm then you. should not start out with anyti. depressants you should start out with.

Lifestyle Changes like changes in your. diet exercise again right um getting. good sleep just stuff you can do without. Pharmaceuticals everyone agrees except. I'm sure for the pharmaceutical. companies that you should not start with. that for like lowlevel depression yeah I. I was curious too about kids about I. wondered if that was just a minimum age. and from what I found each drug is FDA. approved starting at a certain c age mhm. what's the youngest you found uh mostly.

the youngest I found was seven years old. I would have guess five yeah I mean. there that may be but uh I just found. seven uh so there's just a couple of. other things we want to cover real quick. that fall under the umbrella of anti. depressants making depression worse. right because you would probably be. bewildered if you were taking anti. depressant and you're like I actually. feel way worse than I did before and. there's a whole kind of little Suite of. possible reasons for why that might. happen yeah I mean you may be just it.

may be simple misdiagnosis um it could. be bipolar disorder it could be uh BPD. which we've talked about borderline. personality disorder uh but those are. not the same things so you just might be. misdiagnosed yeah you might have a chump. for a doctor yeah um genetics is also. one apparently that also determines. whether you have whether a risk factor. like you said earlier like grief or. something like that pushes you into.

major depressive disorder um there's a. gene the SLC 64a the serotonin. transporter gene I think there's a. variation in that where you can actually. get feel worse after taking. anti-depressants because of that Gene. yeah uh your metabolism might affect it. if some people just don't clear drugs. out of their system as quickly yeah um. so if if if it's taking longer than. usual then usually a dose adjustment can. help with that but that could imbalance.

things even more yeah and then uh being. under 25 before your brain is fully. developed that's one there's something. called. athesia um which it's basically just an. internal restlessness that keeps you. from sleeping makes you anxious and then. those will um make your depression. symptoms worse and then just being on. too many drugs right yeah poly Pharmacy. uh pretty good band name um but not a. great thing to live with because uh you. know things interacting with other drugs.

is a real thing and if you're if you're. on a lot of them then it's some kind. sometimes can be hard to even uh tell. what might be affecting what you a get. at a certain point right. exactly so that's it for. anti-depressants right you got anything. else I got nothing else okay well go. forth and uh seek treatment if you have. depression especially if you think you. have major depressive disorder go get. help things can get a lot better and. since I said things can get a lot better.

everybody it's time for listener. mail uh this is one of a couple I'm. going to read in the next few episodes. about the inner monologue episode we. heard a lot from people about that yeah. uh and specifically in this case my um. inner monologue when I'm falling asleep. getting really weird uh Hey guys Chuck. mentioned before falling asleep his. thoughts start to get weird and that's. how he knows he's falling asleep right. away an he was talking about uh and the. reason I read this one cuz I had dozens.

and dozens of people that have the same. thing it's cuz it's very common but this. person names it there's a term called. hypnogogic imagery H uh which I think. we've talked about that in something it. might have been lucid dreaming it's got. to me uh which I learned about from Jeff. Warren's awesome book The Head trip it's. basically the stage before falling. asleep when her brains start to produce. hallucination likee images this happens. to me though I'm not consciously aware. of it on nights when I fall asleep. quickly uh often I'll drift into the. hypnogogic stage and then catch myself. and think that was weird uh which is.

what happens to me and then drift back. in Chuck described his experience as a. series of nonsensical thoughts so I. wonder uh if his is truly verbal versus. visual I would love to hear more I think. mine are a little bit of both Jill and. that is Jill in Connecticut thanks Jill. that was a great one we love naming. stuff that we experience and didn't know. there was a name for right. right so uh okay well if you want to be. like still send us an email uh send it. off to stuff podcast iheartradio.com.

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