Psychiatrist Tells the Truth About Anti Depressants

as we've done more and more studies on ssris what we've sort of found is that the effect of ssris seems to be smaller than we originally thought and that the effect of ssris is a little bit more complicated than we understood let's talk a little bit about antidepressants and specifically ssri medications so the first thing to understand is that there's a you know there's a clinical illness called major depressive disorder unipolar disorder depressive disorder bipolar disorder so these are mood disorders so these are like fluctuations of our mood that tend to be so severe that they cause some kind of impairment in function so everyone experiences sadness everyone has low energy kind of days but what we've noticed in the field of medicine is that for some people these symptoms are very persistent so they'll last for weeks months or even up to a year or over a year at a time and that they're so bad that they make it difficult to live a normal life so it's difficult to engage in social relationships difficult to get your work done difficult to go to school you'll sort of experience negative things like energetically so like your body can feel heavy it can feel really hard to get out of bed um other features of mood disorders and depressive episodes are changes to your sleep so sometimes people will sleep too much 14 hours a day 15 hours a day sometimes people will sleep too little they'll wake up at 4am every single day like with their mind being very anxious and having trouble going back to sleep so we know that there are clinically present these this exists that depression is some kind of illness we also know that it tends to strike particular people so a key thing about mood disorders at their is that they're episodic in nature so i'm doing fine freshman year sophomore year rolls around my second year of uni rolls around and suddenly like i have trouble getting out of bed et cetera et cetera it stays bad for a while but the other thing about depressive episodes is that they tend to resolve over time so one thing to remember is that depressive episodes are not necessarily a diagnosis so you can have a depressive episode as part of a major depressive disorder or a bipolar disorder or related to other things what we're going to be talking about today is a little bit about ssris or antidepressant medication how they work what they do and what their limitations are so before we dive into this one thing that i want to share with y'all is um a paper that came out recently from the the journal nature which is a very high impact factor nature i mean a paper a journal so high impact factor means that it tends to be cited a lot generally speaking it's a high quality journal with high quality evidence and a paper came out recently that suggested that the serotonin theory of depression is actually somewhat false so for a long time people have been saying that major depressive disorder and bipolar disorder and depressive episodes are caused by a neurochemical imbalance in a deficiency of serotonin in the brain and what this paper basically demonstrates is that the quality of evidence that suggests that there is a neurochemical imbalance in the brain that causes depression suggests that the quality of evidence is like low or inconsistent and the paper basically makes the argument that actually this neurochemical imbalance theory is essentially false so this is important to understand for a number of reasons so the first thing is when this paper came out there was a lot of popular media interest in it because people were sort of saying oh like the neurochemical imbalance theory is false and then they would interpret that statement in a number of different ways so that one of the primary interpretations is that if the neurochemical imbalance theory is false that means that antidepressant medication doesn't work or that we've been scammed for the last 30 years by big pharma and drug companies that have been peddling this medication that is based on a theory that is actually incorrect so we're going to talk a little bit i don't really think that that's a fair interpretation we're going to talk a little bit about that but let's first talk a little bit about the neurochemical hypothesis of depression so basically in the 70s and 80s psychiatry experienced somewhat of a revolution and we discovered that there were actually like there was a biological side to psychiatry so prior to the 1970s and 1980s psychiatry was primarily a psychological discipline so it was like freud talking to people interpreting things about the subconscious etc etc and as medical advances improved psychiatry sort of developed this kind of biological side which means that there's like neurochemicals involved there are medications involved and when fluoxetine the first antidepressant or ssri came out people thought it was pretty revolutionary because for you know the last hundred years we really haven't had medication treatments for things like clinical depression and suddenly we've got one and it seems to work really well so it's important to understand though that when we developed antidepressant medication we did not develop antidepressant medication as a response to understanding the mechanisms of depression so it wasn't like we figured out oh by the way depression is caused by a deficiency of serotonin let's try to fix that deficiency of serotonin with a medication what actually happens usually in medicine which a lot of people don't realize is we don't really know why a medication works we just sort of know that it works okay so we'll try a lot of different things we'll do clinical trials some of these things are based on herbs and stuff like that so like we'll know historically for example that we have an herb called saint john's wort which has been shown to be clinically effective to mild to mar for mild to moderate depression we'll kind of study saint john's wort we'll see like okay what's the chemical compound that's responsible oh it seems like the chemical compound that's responsible boosts serotonin so let's see if we can isolate it purify it etc etc so one thing that kind of happened early on as we studied ssris and we sort of realized that they're somewhat efficacious and we'll get to that in a little bit so we discovered antidepressant medication works and then what happened is like there was this big movement to destigmatize mental illness because prior to this mental illness was basically viewed as a personal deficiency right if you if you have trouble getting out of bed because you're depressed that's just laziness and so one of the key things that was very very helpful in destigmatizing mental illness was this neurochemical imbalance hypothesis oh it's not your fault you're not lazy like you just have a neurochemical imbalance and by the way we have clinical trials that show that antidepressant medication works so the interesting thing about the neurochemical imbalance hypothesis of depression is that i don't think that psychiatrists or scientists if the people who are really educated really ever had or necessarily believed that you know neurochemical imbalances caused depression and the key thing to remember is that neurotransmitters do all kinds of stuff in our bodies right so we sort of think about popularly we'll sort of associate dopamine with pleasure we'll associate serotonin with mood and there are some connections but remember that serotonin and dopamine do all kinds of different things so parkinson's disease which is a disease that affects dopaminergic neurons in our brain makes it difficult for us to walk right so like our motor movement anytime i move my hands that's governed by dopamine a lot of our peristalsis so the ability of food to pass through our gi system that's actually also controlled by serotonin so serotonin does a lot of different stuff and just because the neurochemical imbalance sort of theory may not be as strong or may even be false does not actually say anything about the efficacy of antidepressant medication because we have clinical trials that even if we don't know how it works we still have evidence that ssris or antidepressant medication are effective for depression so this is one distinction or nuance that i think has been completely lost in the common media right so we we don't know exactly we'll get to the mechanisms of action explain why even though there may not be a neurochemical imbalance how boosting your serotonin in the synaptic cleft can still be helpful to for depression so we're going to take a step back and just let's recap okay so for a long time recently actually people have thought that depression is based on a neurochemical imbalance we also know that boosting serotonin seems to improve symptoms of depression and actually a key thing there is that remember that the the hypothesis of neurochemical imbalance has actually grown a lot more after we started using antidepressants or ssris and what people basically did is reverse engineer that hypothesis and sort of concluded that okay if i boost someone's serotonin if they start to get better then that must mean that serotonin is deficient in the brain but it actually turns out that that really isn't the case so let's dive in and try to understand a little bit about antidepressant medication and kind of how it works so here's just a google search for the synaptic cleft okay so what we we can do is kind of look at um you know pictures of i don't know what this is but the synaptic cleft so let's try to understand how antidepressants or ssris work so this is um something called a synaptic cleft which is where two neurons or nerve cells meet and in the end of one neuron we have these little things called synaptic vesicles so these are little packages of neurotransmitter and generally speaking what happens is when this neuron activates with an activation potential we'll get it the the vesicle kind of merges with the synaptic cleft and dumps out the serotonin the serotonin floats across this gap and activates some stuff in this receptor so this is kind of how uh synaptic cleft works over time these molecules will then get taken back up into the cell so they'll kind of return where they came from get repackaged into vesicles and essentially recycled so we'll send out a signal and then we'll kind of recycle it so the most common antidepressant medication is called a ssri which means select selective serotonin re-uptake inhibitor so essentially what an ssri does is blocks this receptor and when we block this receptor this stuff can't go back into the cell and floats around longer and increases the signal over here okay so it essentially boosts the serotonin transmission signal in the synaptic cleft thus effectively increasing the serotonin signal between two neurons and when we use this kind of a drug essentially what we discover is that people with depression seem to get better people sort of think about serotonin as kind of like a direct dose response sort of effect and what does that mean so if we think about like other kinds of neuroactive substances like alcohol what we sort of think of is that okay once i you know if i have one drink versus two drinks versus three drinks versus four drinks the more drinks i get the more intoxicated i become but it turns out that the action of ssris or antidepressant medication is actually a little bit different so it's not like doubling our serotonin doubles our happiness if we look at the mechanism of ssris what we discover is that they create a lot of cellular machinery changes so it's like boosting the serotonin signal doesn't make us twice as happy what it actually does is turns on some machinery within our cells so it activates gene transcription so it starts our cells start producing more machinery it affects our receptors so the effect is a little bit more long-term what does that mean practically what it means practically is that when you take an ssri it's not like alcohol where if i drink three shots of alcohol over the course of three hours that i will notice the effect right away in fact the studies on ssris show that ssris take anywhere between one week and eight weeks to work so this is something that's really important to remember about antidepressant medication is if i feel super depressed and i take it today tomorrow and the next day i may not notice any kind of effect and why is that it's because it's not a direct boost to serotonin it's because we're turning on certain cellular machinery we're activating particular genes so for example one of the things that we know is that ssris create more proteins that are neuroprotective for our brains so they'll activate so they'll create these kind of protective proteins in our brain and those may take time to work so the the action of ssris and antidepressant medication is actually weeks so this is important to understand because if you start an ssri or antidepressant medication you may not notice a benefit right away this becomes doubly important because sometimes the side effects of antidepressant medication we do notice right away so for example people will sometimes feel a little bit nauseous or have some upset stomach and that's because remember serotonin is in our gut as well and as we boost serotonin transmission we can sort of mess up our tummy a little bit but the key thing to remember about antidepressant medication is that it can actually take weeks to work and so even if you're not really seeing a benefit right away that's actually perfectly okay it can take a couple weeks so let's try to understand a little bit about the efficacy of antidepressant medication so a lot of people will be kind of you know curious or concerned about how effective antidepressant medication is people will be concerned that they'll be hooked on it and that it sort of is a happy pill and sort of creates an artificial sense of happiness whereas the truth is that really isn't the case so people have also been concerned that you know there's an over prescription of antidepressant medication especially during things like the pandemic and that essentially like you know big pharma is trying to get everyone to take antidepressants and they may be trying get getting everyone to try to take antidepressants i can't really comment on what they're doing or not doing but the the good news is that the data for ssris and antidepressants is pretty good right so we know for example that if you start an ssri that you can expect somewhere between a 30 and 50 improvement in your depressive symptoms over the course of one to eight weeks so it's not going to make you magically happy by the way ssris are not drugs of abuse so a lot of people will think that if i improve my depression it's like making me happy it doesn't make you happy it really seems to resolve the depression but it's not like ssris create any kind of euphoria you don't hear you know ssris don't have any street value people aren't abusing them because they actually are happy pills those are substances of abuse things like amphetamines cocaine you know even alcohol benzodiazepines marijuana like so ssris really aren't happy pills what they really seem to do is reduce the frequency and severity of depressive episodes so what we know is that when people start them you'll get sort of a 30 to 50 improvement in depression now the other thing that that i kind of want to point out is that as we've done more and more studies on ssris what we've sort of found is that the effect of ssris seems to be smaller than we originally thought and that the effect of ssris is a little bit more complicated than we sort of understood so here's just one example of kind of the nuances of antidepressant medication and this is a good example of how antidepressant medication a lot of it seems to be based on belief so as people are more hopeless or if they think that an ssri will not work it actually reduces the efficacy of the ssri so some people even have even hypothesized that 70 or up to 70 percent of the therapeutic value the clinical benefit of an antidepressant medication is actually placebo and only 30 percent of it is biological now if i say something like that y'all may be very very surprised because you may say well like you know if it's placebo does that mean that it's not effective and i shouldn't take it whereas not necessarily in fact what we sort of know is that even if it's placebo we sort of still know that it knows know that it works and there are even studies that show that if you tell a patient this is a placebo but you also tell a patient that placebos lead to clinical improvement giving that person that medication even though they believe it's a placebo if you tell them hey i think this ssri is going to help you even if it's a placebo it turns out that it actually works and it helps them so knowing that something is a placebo doesn't actually remove its effect as long as the patient understands that placebos can actually be helpful so we we sort of know that ssris may not be quite as efficacious as we thought so here's kind of my clinical experience on it so what i'd sort of say is when you when we look at a 30 to 50 percent improvement which is what most of the meta-analyses show about antidepressant medication what we discover is that that's an average right so we'll take a hundred people and on average we see a 40 improvement but more specifically if you're a clinician and we saw this a lot during covid what you actually see is that it's not actually a 40 improvement for all 100 people that there are people actually fall into three camps so for about a third of people ssris are very very effective so we're talking 70 improvement 80 improvement 90 improvement really kicks the depression to the curb for about a third of people they're like moderate lead to mildly helpful we'll see that sort of 30 to 50 range it does seem to help but it doesn't really cure my depression and for about a third of people it really doesn't seem to help at all and this is what we've seen a lot as we've sort of seen the nature of depression changing is that a lot of depression now seems to be very circumstantial or existential in nature so i'm like covet is happening i lost my job there's inflation there's climate change all these kind of existential factors if those are leading to our depression it seems that ssris are not really effective at helping that the key thing to remember here is that that 30 to 50 number is probably due to multiple different kinds of depression within a population and that antidepressant medication is very very helpful for about a third of people and for the other third of people it helps some so we're still talking about a success rate for about let's say two-thirds of patients in my clinical practice that's kind of what i'd say historically that i've seen but that's another important nuance so the last thing that we're going to talk a little bit about in terms of antidepressants is a lot of people are really curious or concerned that if i start an antidepressant medication am i going to be stuck on it is this the kind of thing that i will then be dependent on as a happy pill and the evidence here is actually like pretty interesting so it turns out that if you start someone on an antidepressant medication they should stay on it for probably about a year so for a lot of people who go off of antidepressant medications about 50 to 60 percent of people who go off of antidepressant medication will depending on how they go off and what other kinds of things that they do they'll experience depression again later in life so within about one to two years about 50 let's say half of people who go off of antidepressant medication will be depressed at kind of two years out but what that also means is that about half of people actually even if they'll really only need ssris once in their life and they'll kind of be okay after that so in no way is an antidepressant medication something that you you'll become dependent on for the people who require antidepressant medication for longer periods of time these are people who tend to experience frequent or severe depressive episodes so remember that a depressive episode is it's an episode so it's kind of time limited so generally speaking the people who are on ssri's long term are the ones that will tend to get depressed over and over and over again and this is also important to remember about ssris or antidepressant medication is that it kind of reduces the severity and frequency and duration of episodes so if you're someone who struggles with depression and you're on an ssri versus not on an ssri you're less likely to get depressed in the first place if you do get depressed the severity of that depression it won't be as bad and you'll stay depressed less right so like one person may depress be severely depressed for eight months and they'll get one episode of depression a year versus someone who's on an ssri may get depressed once every three years for a period of two to three months and it won't kind of be as impairing so the goals of ssri treatment are really sort of reductions of duration frequency and severity of depressive episodes now the other thing to remember about ssris is that they oftentimes do have side effects the good news is that side effect profiles for ssris are some of the best tolerated in medicine that's part of the reason why we sort of prescribe them as much as we do because most people will take an ssri and not even notice anything they may have a couple of days of like some sort of change maybe like a little bit of fogginess a little bit of headache a little bit of upset stomach but that tends to go away within a week so they tend to be tolerated really really well one other thing to remember about ssris and this is where a lot of people run into problems is that you have to be a little bit careful about coming off of ssris so a lot of times what patients will do is they'll take the ssri when they're very depressed because they'll do anything to get out of the depression they'll start to feel better two or three months later and they'll be like i feel fine every day i don't need to take this medication it'll kind of stop it so that's something that you should definitely talk to your doctor about because there's some evidence that shows that ssris need to be tapered so you can't just kind of quit cold turkey i mean you can but you really shouldn't you should really sort of go off it sort of smoothly and when you taper it properly it also helps in terms of not having a relapse of your depression and you also have to consider that sometimes the reason that you're feeling good every day is because you're on the medication right so this is sort of like someone who's like wow i feel really healthy because i'm i'm eating healthy every single day and i feel really fit and i have tons of energy because i'm working out and i'm i'm eating healthy every single day and so because i'm healthy now i no longer need to exercise or eat healthy right so something you have to really remember about antidepressant medication is if it helped you get to where you are you may want to consider staying on it for a little bit longer or at least talk to your doctor about it as always when it comes to details of okay does do ssris work for me or not work for me you know should i use them should i not use them here are my concerns you should always talk to a doctor about starting them stopping them talk to your doctor i think it's very very common as psychiatrists we hear all the time that people don't want to be on their ssri so it's absolutely something that you can do in sort of like a low risk fashion right so you want to be monitored as you come off of it to make sure that symptoms don't emerge re-emerge and there are other things that you can start to do instead of ssris that will sort of keep you mentally healthy so that's kind of our brief discussion of ssris or antidepressants we started off talking a little bit about the neurochemical imbalance hypothesis and some of the associations that people make with that so there's a recent research that shows that depression is not actually clinical depression is not actually caused by a neurochemical imbalance and so a lot of people will interpret that as oh my god that means that antidepressants don't work whereas the truth of the matter is that we don't really know sometimes why our medication works in medicine and every day that goes by we discover some new effect of a medication we'll discover off-label uses it turns out that ssris are also helpful for anxiety we didn't really know that originally but what we do know is that ssris and antidepressant medication does seem to be effective and those clinical trials haven't changed just because depression may not be caused by a neurochemical imbalance we also know that that ssris tends to take some time to work so we're talking somewhere between one to eight weeks to reach full efficacy and we also know that sometimes people do need to be on ssris for extended periods of time sometimes two years three years four years but that a lot of people can actually safely come off of ssris and you're not going to be dependent on it for the rest of your life so hopefully that's kind of useful hopefully it's sort of a quick introduction to antidepressant medication how it works how it doesn't work and um you know by all means if you're interested talk to your doctor about it questions okay so someone's asking about thoughts about someone who has ptsd and depression who ssris don't work for so a couple of things to understand about ssris in terms of when they quote unquote don't work so the most common reason actually i don't know about the most common reason but one of the most common reasons that ssris don't work quote-unquote is because there is another thing going on that interferes with the efficacy of the ssri so a good example of this is something that we call dual diagnosis in psychiatry so we made some interesting observations as clinicians that when someone has let's say a substance use disorder like they're addicted to alcohol or marijuana and they have depression that you can't treat one of those on its own so for example if i start someone who has an alcohol problem on an ssri or antidepressant medication that may help some but the alcohol itself if i'm drinking every day that's going to cause depression so we know for example that al alcohol can induce a depressive episode so we know that alcohol kind of makes us kind of feel down on ourselves can can sort of acts as a a cns a central nervous system depressant it literally like slows down the transmission in our brains and so as long as we're sort of drinking the ssri doesn't seem to work the other thing that we know is that when people are alcoholics and they have an untreated depression that can make it hard to become sober so i use alcohol as a coping mechanism and i become sober for let's say six months and then the depression kicks in so even though i've been sober i have a separate process going on that makes me feel depressed and until i sort of take care of that process when i start to feel really really depressed and down on myself what do i start doing i start drinking so what we know from dual diagnosis is that you can't sort of tackle one problem at a time and that good treatment actually involves sort of addressing the depression because if you get depressed you're going to start drinking and addressing the alcohol use because if i start drinking i'm going to get depressed right so if i start drinking i get written up at work people get upset with me in my personal life that lowers my mood makes me feel depression can kind of trigger a depressive episode so for people who have multiple diagnoses i would be super careful about thinking that something quote unquote doesn't work probably what you need is treatment for both diagnoses simultaneously for that antidepressant medication to work that being said remember that sometimes especially when it comes to trauma uh illnesses trauma can be sort of the great masquerader so it's like the the great chameleon and trauma can look like all kinds of other things so sometimes i've seen people who are you know get diagnosed with a major depressive disorder or unipolar depression or bipolar depression and actually what they've got is some form of ptsd or complex ptsd or something like that which can look like depression so trauma you've got to be really really careful about because it can really interfere with all kinds of stuff and even look like all kinds of stuff you may not even have depression you may just have trauma that looks like depression so i wouldn't give up on ssris you know just because you had a trial and it sort of didn't work you know i would really think a little bit about getting into good treatment that tackles kind of everything at the same time sort of a comprehensive personalized treatment plan with like a really good medical team doctor and um and and really then sort of determine whether ssris work or don't work a couple of other things to keep in mind there have been studies that show that even if the first ssri or antidepressant that you tried doesn't work that about half of people will see a good response from their second trial of an ssri so if you've tried one and it didn't work and you try another there's about a 50 chance that that'll actually work well the more trials that you have the lower your success rate is so for your third trial maybe about 20 percent of people see a a pretty good benefit from it and so there are people for whom ssris don't seem to be very effective and that's we kind of know that yeah so you ukulele is talking about there's there's a really interesting black box warning here in the united states that starting an antidepressant medication actually increases the risk of suicidality in younger adults or teenagers there is actually there was an observation that teenagers and young adults who get started on antidepressant medication for a brief period of time actually have a higher increase an increased risk of suicidality and suicidal behavior so this is a really interesting black box warning i think there's a lot of complexity to it and they're kind of two i think prevailing theories that i put stock in the first is from a public health standpoint let's start by sort of saying that just because you started an ssri be aware that you may actually increase uh get increased feelings of suicidality or suicidal behavior so it's just something to watch out for and it tends to be like a temporary effect we'll talk about why that is so it's not like it'll increase it over time it's for a brief period of time it sort of increases it and then the suicide alley actually goes down and gets better over time so why could this be there are two primary reasons that i sort of think of right so these are not necessarily correct they're just based on my clinical experience and all the evidence i've read this is sort of where i put my money the first is that there is a selection bias with severity of illness and starting an ssri so if you think about if i take let's say 100 teenagers who are 16 years old who are all suffering from depression who is the most likely to get started on a medication the more severe the illness the greater the likelihood that you'll get started on medication so if i take that 100 you know teenagers who are 16 years old and i split them into three groups a third of people are severely depressed a third of people are moderately depressed and a third of people are mildly depressed they all go see a doctor and so the people with mild depression they don't get started on ssri because their depression is pretty mild oh it doesn't seem that bad i don't need to start you on medication the moderate people some of them get started some of them don't get started and then the severe people they all get started and now what we do is we compare these groups so what is the likelihood of suicidal behavior in the severe people it's actually higher than the mild people so the third of people who all got ssris have more suicidal behavior than people who got no ssris then what we start to do is potentially create a causal link does the ssri cause suicidal behavior or is it a selection bias does that kind of make sense so that could be a one reason for it the second reason which is kind of interesting is that the way in which ssris help us is the different dimensions that antidepressant medication affects work at different timelines so i know that doesn't make a whole lot of sense but let's just take a look at this for a second so if i take someone who's depressed remember that an ssri takes up to eight weeks to work so we tend to see practically when we give someone an ssri is all of their symptoms don't get better all at the same time so depression manifests as low energy suicidality and hedonia which is the inability to experience pleasure sleep problems appetite problems and what we tend to see is that not all these things all of these things get better all together and so sometimes what actually happens is the energy level actually increases first so people will start sleeping better they'll start eating better they'll have a little bit more energy and some of the more cognitive stuff like the suicidality the feelings of guilt the feelings of shame some of that stuff takes longer to get better so what some people have hypothesized is that we actually see a boost of energy before we see improvement in the suicidal thinking so if i have two suicidal individuals and one of them has low energy and one of them has high energy who is more likely to commit suicide or try to engage in suicidal behavior it turns out that maybe the high energy individual is actually more prone to engage in suicidal behavior so one of the really interesting theories about the black box warning is that it actually boosts the energy of people who are still actively suicidal which actually like it kind of bizarrely and their low energy level is actually protective against actually trying to commit suicide so this could be another reason for the black box warning we don't really have a very clear answer i think both of these are really really sort of reasonable hypotheses and the key thing to remember is that when you're starting an ssri just to be aware especially if you're on the younger side so as an adolescent or young adult you may actually experience more suicidality this once again is exactly why you all should talk to doctors about it because there are going to be a ton of other things to consider in terms of side effects and stuff like that great question you

Channel: HealthyGamerGG

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Length: 34min 59sec (2099 seconds)

Published: Mon Sep 12 2022

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[u/seven_seven]

I don’t think doctors consider the long term downsides of SSRIs when they prescribe them for patients after a 10 minute appointment.