So what happens when you take antipsychotics? Anti psychotics famously block the D2 receptor here. It’s one of the defining attributes of an antipsychotic, which is helpful because if I take a medicine that blocks this section here and then me’s Olympic pathway, it’s gonna prevent my psychosis from firing off. That’s a good thing. We don’t want the psychosis to go, but it doesn’t know the difference between a D2 receptor here and a D2 receptor here.
It’s just hidden D2 receptors everywhere. So if we go back to our fun movement pathway, if we block this guy, we just took the breaks off the system. Remember, you hit the D2 receptor, it slows everything down. So that means D1 receptor is just going unchecked. And he’s like, go, we can only turn the gain up. So if I take a medicine, I turn the gain up way too fast. That just means gas, all gas, no breaks, risk gonna fire all the way.
My arm’s gonna go on this or my next thing else. And that’s what we call a cute dysonia. That’s actually really bad symptom that could happen when you first take an asthetic.
If you block these receptors for a long enough period of time and you’re having issues, you can get essentially a parkinsonian type syndrome from this D2 blockade because the same effect is happening. You’re blocking the dopamine receptors to s keep psychosis at bay, but at the same time, you’re still hitting the substantial nigres. So it’s gonna lead to some parkinsonian symptoms. And if you take antipsychotics for a long enough time and they’re always blocking these receptors, you’re just gonna keep making more receptors. And this means it’s gonna be harder to simulate this neuron.
And so this is, there’s gonna be a mismatch here no matter how much dopamine I produce, I’m not gonna be able to meet all these extra receptors that are striding up. Cuz I’m like, all right, I’m just going terminal. You keep blocking those receptors, I’m just gonna make so freaking many of them. I don’t even freaking care. And now that there’s too many receptors to try to satisfy, we get an issue here where this will never be fully firing properly. That is something called tardive dykinesia, gets to the point where everything.
Your long term compensation for this just becomes so discornate that you’re always just kind of moving around. So what we see a lot with Hard Live is this conjugate movement and lip smacking is really common. It kind of looks like I’m not doing very well, but it’s kind of like.
That in the old days, we used to just give more antipsychotics where like too many these are popping up. Let’s just go, let’s knock them all out and it would help with the symptoms for a little bit. We’re.
Like, nice, we’re back to where we were. But then you just brought.
Up more receptive. Your body’s like, I can play this game all freaking day. I’ll make even more of them. And then you just get right back into tardive. So what we do instead, actually, is we try to recover some of our dopamine. Remember for this VMAP vessel up here, we actually inhibit the reuptick into it a little bit. It’s just enough to get the edge off. And so that gives us some more dopamine here. And that actually helps balance, bounce this out. Female inhibits are so subtle. They’ll help with the tar dive, but it’s not enough to put you into psychosis. It’s just a little bit on the edge.
Now you have to remember that not all anti psychotics are created equal. They all have different affinities for the dopamine 2 receptor, which means they’re gonna have different rates of side effects. These are called extra parameter symptoms. Your parameter track is your intentional motor track. So extra parameter just means outside of your intentional movement, extraneous movements. PS can be associated with the potency of the antipsychotic. So a high potency and psychotic like how doll is gonna have more API symptoms authority, which is lower potency.
When I say potency colloquia, I just want you to think about how tightly the receptor is bound by the drug. If it’s binding it really tight, that’s higher. Potency has nothing to do with the global effect. So they’re the dose you need. So these are the older drugs we had.
Thorium was the first antipsychotic that was ever made. And then how do’s oldest too. And we got a lot of these extra parameters, symptom problems. So what do we do? We made a second generation where we have them atypical. What makes these guys a typical or second gen?
We did this magical thing where we hit the 5HT2A receptor. That’s a serotonin receptor. So if you recall, we’re blocking all the dopamine neurons here, causing downstream motor issues. And that’s because we’re overblocking these dopamine neurons at the synapse level.
We don’t want to give a bunch of dopamine to put someone back into psychosis, but we want to recover just a little bit of our dopamine. So how could we do that? It turns out all of these neurons actually are surrounded by serotonin neurons. Remember, we’re not in a vacuum. Everything here is interconnected, and there’s a 5HT2A receptor that sits on the edge of these dopamine neurons.
What does this 5HTTA receptor do? It’s like breaks. It, inhibits it. So if you activate this guy, it shuts down the whole system. He’s also got receptors appear in the dendrites.
So we have a natural serotonin mediated break sitting on our dopamine receptors. What if we just inhibit that? So if I block this guy right here, I’m taking the breaks off the system and I can recover some of the function of my dopamine receptor. So that means I can recover some of my function here in the nigostrial pathway, and I’m not just going scorched earth on every dopamine receptor ever, keeps you from overshooting the runway, like we were saying earlier, this 5HT2A blockade is the defining attribute of a second gen ant, a typical anti psychotic. Because of that, atypal antipsychotics tend to have less extra primitive side effects.
They have less motor side effects. So they’re often preferred by psychiatrists. There are a million things to consider here. This is just one little lens we’re looking at. You may be seeing all of a sudden thinking, why on earth would someone take an antipsychotic then? This seems like such terrible side effects.
That induces parkinsonanism. You can get targeted dykinesia. Cute to Sonia. Like why are the risks worth it? And I want to impress upon you how much of a burden schizophrenia is to people, the risk of suicide with someone who’s diagnosed with schizophrenia is somewhere between 5 and 13%. That is so high, the life expectancy of someone schizophrenia is reduced by 15 to 20 years by average.
When you have a really nasty disease like cancer, you use chemotherapy, which sometimes can feel like poison. It is a really hard drug that while it takes away cancer, wreaks havoc on your body. I want you to think about schizophrenia like the mental health equivalent of lymphoma.
I’ve had patients that have tardived dyskinesia from clause pine that they take chronically. And when the psychiatrist even broached the idea of going off of clause pine, they were very resistant to it. They said closepin is a good drug for me. I would rather handle the side effects and go back into psychosis. I don’t wanna do that again.
So while I can understand some people have terrible experiences with side effects, other people acknowledge the side effects, but ultimately decide that they’re worth it because of how awful psychosis is and because of how dangerous these drugs are. If don’t wanna use them incorrectly, that’s why I smash my fist when it comes to getting diagnoses, right. If I diagnose someone who has a personality disorder with a psychotic disorder and give them anti psychotic says, I’m creating undo harm. Borderline personality disorder is named so because it was borderline with psychosis, it was so hard for us to distinguish between it. So that means you have to be really good and really careful when you give someone a diagnosis.
Like this is my own soapbox to other psychiatrists and just to myself of like why I need to be good at what I do and why this is so hard. The it’s so freaking hard. I can’t tell you enough.