HealthyGamerGG - Psychiatrist Tells the Truth About AntiDepressants

Episode Date: September 3, 2022

Dr, K talks about antidepressants, serotonin, SSRIs, and more! Support this podcast at — https://redcircle.com/healthygamergg/donationsAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy Learn more about your ad choices. Visit megaphone.fm/adchoices

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, 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. 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 4 a.m. every single day, like with their mind being very anxious and have trouble going back to sleep. So we know that there are clinically present, 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 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 a paper that came out recently from 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 and 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, et cetera, et cetera. 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 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 St. John's Wart, which has been shown to be clinically effective for mild to moderate depression. We'll kind of study St. John's Wart. 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, et cetera, et cetera. So one thing that kind of happened

early on is 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 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, the people who are really educated, really ever had or necessarily believed that, you know, neurochemical imbalances cause 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 peristulses, 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. So we don't know exactly, and we'll get to 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 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 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 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 can do is kind of look at, you know,

pictures of, I don't know what this is, but the synaptic cleft. So let's try to understand how antidepressants are SSRI's work. So this is something called a synaptic cleft. So this is 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, 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 this is kind of how 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 selective serotonin re-uptake inhibitor. So essentially what an SSRI does is blocks this receptor. And when we're 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 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 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 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, getting everyone to try to take antidepressants. I can't really comment on what they're doing or not doing. But the good news is that the data for SSRIs in antidepressants is pretty good, right? So we know, for example, that if you start an SSRIs, 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, 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 I kind of want to point out is that as we've done more and more, 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 have even hypothesized that 70% or up to 70% of the therapeutic value, the clinical benefit of an antidepressant medication is actually placebo. And only 30% 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 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 we look at a 30 to 50% 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 100 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 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 COVID 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 percent, let's say half of people who go off of antidepressant medication will be depressed. kind of two years out. But what that also means is that about half of people actually, even if they'll really only need to SSRIs once in their life and then it'll kind of be okay after that. So in no way is an antidepressant medication something that 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 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. They'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 eating healthy every single day. And I feel really fit. And I have tons of energy because I have tons of energy because I'm working out and 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, 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 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 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, 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 there are a couple of things to understand about SSRIs in terms of when they, quote, 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 alcohol can induce a depressive episode. So we know that alcohol kind of makes us kind of feel down on ourselves, can sort of act as 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 illnesses, trauma can be sort of the great masquerader. So it's like the great chameleon. And trauma can 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. SSRI's, 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 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 try 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% of people see 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 Eucolili is talking about, 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 there are 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 get increased feelings of suicide. 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 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 what 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 is 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 get better altogether. 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 a boost 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 kind of bizarrely in 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.