Newbie Question about how APs work

[DannyBoy]

I've been taking drugs for awhile now, but still admit I don't really understand how they work or what they're doing.

I'm curious about anti-pyschotics. Do they block chemicals? Or are they responsible for increasing certain chemicals or both?

When I see ADs I somewhat understand that they're recycling serotonin for the most part.

It's the APs I don't understand well.

Thanks for input, and if you have a link that would be great as well.

[tommy000]

the theory at the moment is that people with schizophrenia have too much dopamine. so the antipsychoitcs block it to relieve the symptoms. plz be aware antipsychoitcs will only control/reduce your symptoms they will not cure it.

[DannyBoy]

the theory at the moment is that people with schizophrenia have too much dopamine. so the antipsychoitcs block it to relieve the symptoms. plz be aware antipsychoitcs will only control/reduce your symptoms they will not cure it.

ya I got that, but they do multiple things don't they?

Don't some of the APs do things with serotonin as well?

Which baffles me because I take an AD that boosts serotonin.

Also, do people become depressed on APs? Does the dopamine blocking cause this ever? I'm somewhat curious as I believe my pdoc is going to be increasing seroquel to higher dosages.

[tommy000]

the theory at the moment is that people with schizophrenia have too much dopamine. so the antipsychoitcs block it to relieve the symptoms. plz be aware antipsychoitcs will only control/reduce your symptoms they will not cure it.

ya I got that, but they do multiple things don't they?

Don't some of the APs do things with serotonin as well?

Which baffles me because I take an AD that boosts serotonin.

Also, do people become depressed on APs? Does the dopamine blocking cause this ever? I'm somewhat curious as I believe my pdoc is going to be increasing seroquel to higher dosages.

atypicals can also be used for depression such as zyprexa. im not 100% sure but i think they aps block serotonin. old aps dont do this but the aaps might do. ur going to have to get a second opinion on this one coz i dont have much of an idea. sorry. i think aps are actually meant to help with depression not make it worse?

[DannyBoy]

APs are confusing to me. They can halt mania, yet still hold depression at bay?

But if they are used for depression why do they block serotonin? Especially when most ADs are used to boost it?

And can't a lack of dopamine make someone feel depressed?

Maybe I'm looking at this from the wrong angle, it's very confusing....

[tommy000]

APs are confusing to me. They can halt mania, yet still hold depression at bay?

But if they are used for depression why do they block serotonin? Especially when most ADs are used to boost it?

And can't a lack of dopamine make someone feel depressed?

Maybe I'm looking at this from the wrong angle, it's very confusing....

when there is a lack of dopamine due to antipsychotics you get "parkinsons symptoms" tremor, stiff muscles, shaking etc someone correct me if im wrong but cant a lack of dopamine cause extrapyrimdal symptoms?

[tryp]

Hi,

APs, and the atypicals especially, are very complicated drugs, and to some extent nobody is totally sure what they do.

The typicals (Haldol, Thorazine etc,) are a little easier. They mainly block dopamine. Blocking dopamine in certain areas of the brain quashes psychosis. We think that, broadly speaking, psychosis stems from increased dopamine neurotransmission in the mesocortex and limbic system (some places in your brain). They are also slight antihistamines, which is why they make you sleepy, and slight anticholinergics which gives you a dry mouth, constipation, and some things like that. These are great for hallucinations and delusions, and even mania, but not amazing at treating things like depression. Since they are so strong and non-specific about their dopamine action, they cause a lot of side effects to do with motion. There's a place in the brain called the basal ganglia, and this area controls both voluntary and involuntary movements. It also uses dopamine to communicate. Since the typicals are so indiscriminate, they block this area too and you get EPS and the movement related side effects.

You can think of the typical antipsychotic as a very effective, but very dirty, bomb. It basically slams in and trashes the joint, at least where dopamine is concerned. Sometimes that's what you need - it hits hard and fast, and it's good at what it does. But in exchange, you get more side effects.

The atypicals are more complicated. They do a lot of different things. They do block dopamine, just like the typicals, but they are a little more discriminating in terms of where and how much of that they do. There are many kinds of receptors and places in your brain that use dopamine, and the AAPs can have some very specific modes of action because of those different "flavors" of dopamine use.

We aren't totally sure yet why the AAPs cause less EPS than the typicals. One theory is the fast on, fast off theory. Antipsychotics are mostly involved with blocking D2. The typicals hit it hard and stick there for a long time. In fact, the dopamine receptors like those drugs even more than they like dopamine. So if that drug is in there, dopamine is totally screwed. The atypicals, on the other hand, bind it with low affinity (they aren't too great at grabbing those receptors and they don't stay on them for too long). The receptors would prefer to have dopamine, even though they still like the atypicals a fair bit. For that reason, the atypicals still help with psychosis, but they allow dopamine to work more normally in other areas of the brain because there is an aspect of compromise or interplay rather than total domination. So you get less nasty side effects.

The atypicals, unlike the typicals, work on serotonin as well as dopamine. We're not sure, but we think that the serotonin-dopamine balance might have something to do with the way these medications work. Different atypicals have different effects - the atypicals are a very heterogeneous class of medications - and can affect these neurotransmitters to different extents.

It's not always as easy as "unblocking serotonin receptors = less depression, blocking serotonin receptors = more depression". For example, Seroquel blocks certain serotonin receptors, true, but this can actually increase levels of some neurotransmitters. For example, seroquel blocks a serotonin receptor called 5HT2C, and when that receptor is blocked, you actually get MORE of certain other neurotransmitters that help with your mood. The effect of blocking serotonin receptors depends on what specific receptors are being blocked and where they are in the brain.

Let's look at an example of how complicated receptor blocking and unblocking can be. Some receptors are actually what's called "autoreceptors". This means that the chemical that communicates with them is the same chemical whose levels they regulate. For example, the serotonin autoreceptor. It's purpose is to make sure that serotonin doesn't get out of control. If it senses serotonin, it tells the brain "hey, we already have enough serotonin in here - shut it down". Blocking this receptor, although it is a serotonin receptor, would actually result in MORE serotonin activity in that part of the brain.

Neurotransmitters are very complicated. They are used in very different ways depending on the location in the brain and the specific receptor they are binding. A lot of drugs act on various receptors rather than on the transmitter itself. That is why the action of AAPs is so complicated. They do a lot of different things and they are specific about where they do them. The anti dopamine action helps with mania and psychosis, while the effect on serotonin helps with depression and anxiety.

The effects are also very dose dependent because of a difference in how much the drugs "like" to do the different things they do.

Suppose your favorite thing to do is fish, but you also like bike riding and playing soccer, and you're okay with basketball if you're really bored. If you have an hour or so of free time, you'll probably go straight for fishing. But if you've done all the fishing you're going to do, you might bike for a while or play soccer. If you've done all those things and you still have free time, maybe then you'll play basketball.

The atypicals are like that. Let's look at Seroquel. The first thing it does is to hit histamine receptors (this is ballparked at something like below 100 mg). If you take more seroquel after that, the histamine receptors are all full, so it starts to hit serotonin and some of the other junk. Then, if you take even MORE, it'll start to go after dopamine. This is why it's given for sleep at very low doses, depression/anxiety at moderate doses, and psychosis/bipolar at the higher doses.

All this to say, it's a long story, and even the experts aren't so sure how these things work. But the effects can depend on everything from dose to the specific receptors hit to the specific areas in the brain hit. That's why these drugs are so unique.

And yes, some people can have problems with depression on the APs because of the dopamine blocking action. This is especially an issue at higher doses. The Atypicals tend to be gentler than the typicals, though, and many people do well on them for depression.

[koali777]

I always had to be on an antidepressant when I was on an antipsychotic, regardless of if they were supposed to hold depression at bay. I mean, logically, if something is blocking dopamine, it's not like you're going to have extreme pleasure in anything. I have noticed that some people have been able to deal with it better than I have been able to though...some are on APs for years, while I could never make it more than 6 months. I just couldn't stand not ever being happy. I was docile, yes, but not HAPPY. I have heard that things like Risperdal and Abilify help with the depression...or they're supposed to...just made it worse for me! I'm fine with Pristiq only.

[Velvet Elvis]

More complicated answers are here:

http://neurotransmitter.net/

although it's getting to be a few years out of date in places.

I'm working on a more detailed answer to this and the EPS question dealing with hormones and dopamine pathways but my own dopamine deprived brain isn't working too well.

Recommended reading is the Essential Psychopharmacology series by Stephen Stahl in the crazystore if you really want to understand the nuts and bolts of this stuff. That's what I'm working from.

[Pamito]

Tryp,

Your post was really interesting. I was on Seroquel for 10 years and you taught me stuff about it I never knew, so thanks! It explains why I had to end up taking around 1200mg when the psychosis wasn't arrested. It also explains the intense sedation from it hitting the histamine receptors first. Thumbs up for the info

[conundrum]

APs are confusing to me. They can halt mania, yet still hold depression at bay?

But if they are used for depression why do they block serotonin? Especially when most ADs are used to boost it?

And can't a lack of dopamine make someone feel depressed?

Maybe I'm looking at this from the wrong angle, it's very confusing....

The thing that separates an AP working as an anti-depressant and working as an anti-psychotic.

A low dose of an anti psychotic will antagonize the PRE synaptic D2 auto receptors on dopaminergic neurons. The auto receptor is like a switch that tells that neuron to stop producing dopamine. When dopamine binds to this auto receptor it tells the neuron to stop releasing as much dopamine. So if you block dopamine from getting to this receptor the neuron will continue to release dopamine. This can help with depression.

The flip side is that if you take a higher dose you start to block POST synaptic D2 receptors and D3 and sometimes D1 which are associated with drive, motivation, cognition, and reward. By blocking these receptors you prevent mania and psychosis but you can lose the antidepressant efficacy, especially if you're not manic. Blocking dopamine is also associated with weight gain, and can make one feel their mind is slowed down(which can be helpful for some). This is also what can cause TD symptoms including movement disorders.

The atypical anti psychotics block some serotonin receptors mainly the 5HT2a and 5 HT2C receptors. Under normal conditions when serotonin activates, or agonizes this receptor, it acts as a brake on the release of norepinephrine and dopamine in the prefrontal cortex and possibly in other areas. So if you block this receptor you disinhibit the release of norepinephrine and dopamine in those regions. Drugs that agonize the 5 HT2A receptor can cause hallucinations so I guess this may be part of the theory of how they can help with dellusions.

Like tryp said the negative aspects of atypicals APs are supposed to be less than typical, but the risks still do occur. Talk to your doctor about those and the benefits.

[tryp]

I think that stuff can be pretty situational. I've tried Wellbutrin, and it makes me paranoid, and I can't have benzodiazepines either, but Seroquel is my magic bullet. For depression + anxiety, the AAPs can be a better idea than Wellbutrin or Ritalin or anything activating like that. I'm also Borderline and I really think my Seroquel helps a bit with some of that stuff.

[conundrum]

I think that stuff can be pretty situational. I've tried Wellbutrin, and it makes me paranoid, and I can't have benzodiazepines either, but Seroquel is my magic bullet. For depression + anxiety, the AAPs can be a better idea than Wellbutrin or Ritalin or anything activating like that. I'm also Borderline and I really think my Seroquel helps a bit with some of that stuff.

Yes, I'm sorry for the end of my post. It is a personal thing and I let my feelings on the subject get the best of me. I should not have given my opinion since Danny Boy didn't ask my opinion in the first place and I don't know everything, (as much as I think I do). I'm going to edit that part out of my post.

[conundrum]

I always had to be on an antidepressant when I was on an antipsychotic, regardless of if they were supposed to hold depression at bay. I mean, logically, if something is blocking dopamine, it's not like you're going to have extreme pleasure in anything. I have noticed that some people have been able to deal with it better than I have been able to though...some are on APs for years, while I could never make it more than 6 months. I just couldn't stand not ever being happy. I was docile, yes, but not HAPPY. I have heard that things like Risperdal and Abilify help with the depression...or they're supposed to...just made it worse for me! I'm fine with Pristiq only.

My pdoc prescribed abilify for my anhedonia. At a low dose it gave me energy without a decrease or increase pleasure. At a high dose it just made me feel weird, I can't even put it into words. Everyone is different. (Off topic)Interestingly I just read about how the supposedly selective NRI desipramine actually increases dopamine. http://www.ncbi.nlm.nih.gov/pubmed/6877537. Not sure how that pans out in humans though.