The antipsychotic (atypical or typical) that causes the least cognitive impairment

[etkearne]

So, yes. Most of you know me as the ragingly insane person on the forums of late. I'll try my best to keep this post rational and non-delusional, but be warned.

So, since I have shown many signs of schizophrenia in addition to my bipolar disorder (that are independent of mood), I am starting to fearfully realize that I might need to take an antipsychotic to keep myself from murdering people or committing suicide. I have taken them in the past and hated every second of it.

See, the problem isn't the weight gain or sexual crappola. It is the very clear and noticeable decline in the ability to form abstract associations and think properly. My whole life, since I was a child, has centered around my above-average intelligence. That is all I have ever been praised for, and therefore that is all I identify myself with. Without my intelligence, I am nothing. Just another idiot in the world. So, what is the point of living.

Anyways, to the point of the topic. I have taken Zyprexa, Risperidone, Abilify, and now Seroquel. They rank 1)Zyprexa 2)Seroquel 3)Risperidone in descending order of propensity to destroy one's cognition. I left out Abilify, because it never actually worked well as an antipsychotic for me.

So, what other ones would allow me to keep producing fresh research, intelligent mathematical proofs, etc. , while keeping my blatant insanity under control? The thing that confuses me is that I always hear about people with severe mental illnesses completing med school, law school, grad school, etc. How do they do it? How does someone honestly take 15mg of Zyprexa every night and pump out a doctoral dissertation? Fill me in, please, because I lose sleep over it every single night.

I want to be remembered for something when I die. I don't want to just have my memory fade away in seconds upon my death. I know this sounds very egotistical, but this is the culture that America promotes and I am simply sucked into it.

Please help. For now, I will take Seroquel since that is what my doctor gave me, but I have to learn how to time it so I can perform in school.

THANK YOU

[raincloud]

I had no cognitive problems with Seroquel, but I sure did with Risperidone. Risperidone made my mind and body heavy and sluggish. Awful. As for having a severe mental illness and pumping out a doctoral dissertation -- I don't know. I made it through a master's program, and I don't know how I did it. I don't even feel like I was there or that it really happened.

[bpladybug]

Seroquel (25-50mg prn)

Is that your current dose of Seroquel? That is pretty low, good for insomnia. I don't think that will slow your cognition. Well, especially if you take it at bed time. Does your doctor want you to titrrate up? Maybe you and your doctor can find the delicate balance between controlling your symptoms and maintaining good cognition.

I am taking 200 mgs right now. I am slightly slower in my thinking. But I am on several drugs. I still function, work, and enjoy my life. I think it is possible for you to function in grad school, (is that right?) and control your MI. From my perspective being acutely aware of my moods, and any delusional thoughts so that we can treat it right away is important. That enables me to ultimately take fewer meds. Or at least that is my theory. If I let myself go into mania or depression then it takes more to pull me back to stable.

[etkearne]

Yes. I will be needing to increase the dose significantly if I hope to function whatsoever. Either that, or go to another antipsychotic. I don't know. Even having a little mental slowness scares me. What areas of your cognition do you notice are decreased the most? I am just curious to see if it would be the areas that I need to be in crystal clear shape. Thank you for the replies.

[rowen]

I haven't quite figured out if Abilify is slowing my brain down or if my brain is slowed down because I'm not hypo/manic.

Maybe try Geodon. It's a little more activating for some people, so maybe the lack of sedation will help keep your thoughts in good shape.

[etkearne]

I haven't quite figured out if Abilify is slowing my brain down or if my brain is slowed down because I'm not hypo/manic.

Maybe try Geodon. It's a little more activating for some people, so maybe the lack of sedation will help keep your thoughts in good shape.

Maybe I'll bring it up tomorrow when I see the pdoc. It is the one atypical (other than colzapine) I haven't been on. Well, technically, I have. I was given an IM shot of it at an emergency room once, but I don't think that counts.

[Velvet Elvis]

This is the kind of thing that's going to vary from individual to individual to such a degree that there's really no point in asking. I get zero side effects of any kind off 2mg Risperdal but I've read posts from plenty of other people saying that dose turns them into a zombie. I got no side effects off Geodon either, but there have been plenty of other reports here where people had severe side effects.

I'm afraid the only way you're going to be able to get an answer to this question is to try them all and see. What's true for one person will likely not be true for you and there's no way of using their symptoms or reactions to prior medications to predict how you might respond.

[gizmo]

You know, there was a brilliant mathmetician who really blew everyone away, and everyone knows him for more than his many degrees. Who is he? The Unibomber.

Ok, I shamelessly stole a version of that story from A Good Will Hunting, but you get my drift. Do you want to be seriously fucked up in the head, but brilliant, or normal and able to function with society and not in jail or dead? Seriously, because for you, it may come down to that.

In the years before my diagnosis I was tested and given an IQ of 158. Two years ago when given a simple memory test for the Social Security Administration, I couldn't count backwards by 7's. I still have memory banks of data stored in my head, it's just harder to access and takes longer to do so. Is it the medications? I'm getting off the Topamax, which I consider to be a major player. But my pdocs (yes, there have been multiple) have all told me that the number of mood episodes I've experienced, the kindling, has almost certainly contributed to my mental situation.

So, for now, I rely on my trusty iphone to get me through things which I might otherwise forget. And I continue to take two AAP's.

[Guest Vapourware]

I think it's not only just a matter of your meds having a side-effect on you [although I can't dispute that being a factor, of course] but studying involves more than just intelligence and the impact your meds may/may not have on your cognitive abilities. It's a lot more holistic than that. It's about time management, living a healthy, balanced lifestyle, and it's about your mental and emotional approach to your studies - which is why I think some people are able to complete their studies successfully despite their med cocktail.

I guess what I'm trying to say [perhaps inarticulately] is that the meds aren't going to be the be-all and end-all of your studies. You can take a med that can have no impact on you cognitively and help you control your symptoms, but if the other factors regarding studying have issues then you're still going to run into trouble with your studies.

As for your question - it's really hard to answer because psych. meds can be quite variable according to individuals and also dosage. What works for one person may not work for another. For instance, I know I had a torrid time on Invega and I was on a low dosage, whereas there are people on higher dosages who've been fine.

I've just started on ziprasidone and I've been finding it an okay drug. Then again I'm titrating very slowly upwards so it's hard to tell for sure how effective it is for my symptoms.

[AnneMarie]

Your question is which AP causes the least cognitive impairment. The answer is each person is affected differently. Try them. Med s/e's often wear off with time, so don't bail the first few months. Ramp up slowly instead.

Responsibly manage your illness now so that you can responsibly manage your life.

The point of school is to get a decent job. Employers don't employ crazy even if uni's tolerate differences. Brilliant but homeless math major amounts to living on the street as a loon. No one cares how smart you are unless you can consistently produce. Eratic doesn't cut it in the big bad world. Grow up dude. Now is when you make a committment to sanity, stability and achievement or you are choosing a life driven by the vagaries of illness. You are only fooling yourself. Btw and as said earlier, there are a lot of people here in grad school. There also are those who already hold grad degrees and are employed in their fields. These aren't the med free, freely delusional types. Ya know.

[Guest Guest_001]

Please help. For now, I will take Seroquel since that is what my doctor gave me, but I have to learn how to time it so I can perform in school.

THANK YOU

25-50 mg Seroquel (PRN?) won't have much of an antipsychotic effect, although it can be sedating. Often doctors start people on a low dose and titrate upwards. The idea is probably that as long as you're sedated you don't need the antipsychotic effect as much.

Adderall ? Have you considered that it can cause cognitive problems, perhaps even requiring an antipsychotic ?

Klonopin 2 mg isn't that low either. I know from experience that it can definitely affect cognition.

Then there is the matter of interaction between the various meds.

In some ways Adderall and Klonopin are opposites, they can also have a synergystic effect, good or bad.

You're in the USA ? I believe most people are better off on monotherapy instead of cocktails. That's just a generalization. It can be difficult to know what is caused by which drug, especially long term.

' I might need to take an antipsychotic to keep myself from murdering people ' It's said that caution must be used when prescribing Klonopin to psychotic patients/patients with schizophrenia, since it can lead to agressive behaviour.

You think you may need an antipsychotic. Perhaps the same thing can be achieved with something else. Perhaps an anticonvulsant. Technically not an antipsychotic, but there are drugs that are not antipsychotics that can do the job. There are many options. But anticonvulsants often cause cognitive impairment.

'Anyways, to the point of the topic. I have taken Zyprexa, Risperidone, Abilify, and now Seroquel. They rank 1)Zyprexa 2)Seroquel 3)Risperidone in descending order of propensity to destroy one's cognition.'

Risperidone was not as bad as the others. Zyprexa and Seroquel tend to be more sedating than Risperdal.

Perhaps the sedation is the main problem.

Have you considered a 'typical antipsychotic' ? Newer isn't necessarily better. What about Haldol ? It is somewhat similar to Risperdal, without the action on serotonin. It's very selective for the D2 receptor, perhaps the most selective (dopamine, D2) antipsychotic, it's usually not sedating at all. It might be worth a shot. Another typical and less selective, more calming AP is Thorazine.

Btw, why Effexor ? It is a multiple reuptake inhibitor. According to (http://www.crazymeds.us/effexor.html) low doses work on serotonin, at 200 mg also on norepinephrine, and at 300 mg on dopamine. So why not a real SSRI instead of a low dose of Effexor ?

One last thing. You are young. It's probably best not to focus too much on the diagnosis.

Just passing by, making a few observations without having read your prior posts.

[keops]

antipsychotics reduce concentration power via dopamine supression. this is also the reason they cause EPS, apathy, and sexual dysfunction. theoretically, weak dopamine agents such as seroquel and clozapine are less likely to cause concentration impairment, once the daytime sedation wears off.

[etkearne]

Hello. Back from the doctors. We are keeping the Seroquel in the equation- moving it up to 100mg b.i.d. The reason I didn't ask for it to be changed to risperidone was this weird thing that happened on the way to the doctors. I took 50mg of Seroquel for my rage and anxiety about having to drive 1.5 hours. I had this transformation of sorts to this peaceful and happy state that I have never had from any psych drug before. In fact, it was not too much unlike an opioid. So, I felt great. Still do, in fact. Haven't been worrying or throwing any fits. I don't know what to do. I feel like I should be getting pissed off about something. I told the pdoc about my experience and he implicated the antagonism of 5-HT2C and 5-HT7. Looked it up and it made sense. Very odd, though.

As for being on too many meds, we are going off of Effexor and Klonopin slowly. Hopefully I can get it down to Lithium+Seroquel+Adderall+(prn stuff).

[AnneMarie]

Hey, I'm glad Seroquel looks like it'll work for you. Also glad you have a long term plan shaping up with your doc. Sounds like you're off to a pretty good start for the year.

[dancesintherain]

Glad to hear that you've had a positive reaction to the seroquel! Some times it just takes some time to adjust. And it sounds like you have a really good pdoc who's perceptive about such things and who does a good job of including you in the treatment plan (one of my main goals in any pdoc--the reason I really like my current one). I hope it continues to go well...just don't forget that the increased dose might also have an adaptation period!

[celestia]

Yeah, being really smart isn't all it's cracked up to be. My kid's Dad has two Math degrees but is batshit insane and unable to function AT ALL in society, polite or otherwise.

I actually believe that some of us are too smart to get how straightforward the recovery process is. Take your meds, eat right, sleep, exercise and you'd be amazed at how functional you are.

[Velvet Elvis]

Heh. At 50 mgs. Seroquel shouldn't be much more than an H1 blocker. Real anti-psychotic doses don't kick in until around 400 mgs or more.

[etkearne]

The doctor said we are going to try to straddle the serotonin antagonism and D2 antagonism (so we'll work up to 150 bid- Seroquel's Ki for D2 is around 300mg, so 150 bid). He thinks alot of my agitation and anger are due to the stress and the properties of 5-HT2A, 5-HT2C, and 5-HT7 antagonsim would be very valuable for me. Trust me, I've researched it too.

[Aurochs]

(so we'll work up to 150 bid- Seroquel's Ki for D2 is around 300mg, so 150 bid)

OK, all else aside, how in the world did you get a oral dose value (in g) from a concentration value (in M)? Aside from how you would take into account unpredictable pharmacokinetic variability, converting K_i to an oral dosage means that you no longer have an inhibition constant, and I don't really see how it can be called K_i anymore. And how are two equally-divided doses equivalent to a single dose when trying to maintain occupancy?

[etkearne]

(so we'll work up to 150 bid- Seroquel's Ki for D2 is around 300mg, so 150 bid)

OK, all else aside, how in the world did you get a oral dose value (in g) from a concentration value (in M)? Aside from how you would take into account unpredictable pharmacokinetic variability, converting K_i to an oral dosage means that you no longer have an inhibition constant, and I don't really see how it can be called K_i anymore. And how are two equally-divided doses equivalent to a single dose when trying to maintain occupancy?

First, quetiapine, like clozapine, is a "hit and run" ligand at D2, so you are never going to be occupying D2 in the way a traditional AP would.

Second, I took the average maximum plasma concentrations for 150mg Seroquel (which took some searching- I did it the other day for an unrelated effort, I won't lie), and used that figure.

So, I have (raw data): Quetiapine K_i= 380nM, Quetiapine average (mind you average from what I found) peak plasma concentration for 150mg = 580nM.

So, in conclusion, to get 60% occupancy on D₂, which is the standard for AP relief, I found a dose between 125-175mg, which if given b.i.d., yields 250-325mg per day, which is consistent with the lower end of daily recommended values.

All that aside (sorry, I am a weird person), I found 100mg of quetiapine to be really hard to concentrate on in class today. I am banking on, once the semester starts, being able to go at my own slow, quetiapinated pace to get things done. I actually get ripped a new one by the professor and older graduate student assisting for one teeny error today, but I didn't kill them, so things are moving along in the right direction, I suppose. I am still mad about it, but at least I didn't act on my aggression.

[Artemisia]

I definitely agree about higher levels of Seroquel being less sleep-inducing. That's the story you hear all the time, plus I met a woman on 300 mg (for really bad anxiety), and she complained that increasing the dosage turned out to be pretty counterproductive for her insomnia.

[etkearne]

All I am pointing out numerically, is that, at around 125-150mg of Seroquel, in the average person, D₂ will begin to be antagonized enough to be called a true antipsychotic. Now, clinically, they like to dance around the magic percentage of 75% occupancy. Above that, EPS and prolactin problems occur. So, for Seroquel, that means a dose of around (this is off the top of my head, not my calculations) 200mg. That, of course means 200 b.i.d. since quetiapine's half life is only 7 hours or less. For outpatient pharmacologic therapy, that should be all that is necessary. Of course, it would actually be much smarter to use a more potent AP in an inpatient setting when D₂ antagonization of over 80% is merited. Risperidone would be the atypical of choice there. I have actually done it with Zyprexa: 20mg b.i.d. It worked, but caused quite a bit of EPS.

[Aurochs]

I admit to everything dianthus just wrote. To continue the more theoretical discussion...

I'm confused about how you say that quetiapine doesn't interact with receptors in the same way that other APs do, an admission that K_i values are unreliable, and then turn around and use the unreliable K_i values to calculate an optimum oral dose. I'm also confused about how you rely on average plasma concentration to determine how much of the drug is active in the brain, without reference to lipophilicity or any other measure of BBB permeability.

[etkearne]

If you are aware of another algorithm for finding optimal dosages, please show me, because, without access to most medical literature (which unfortunately is pass word protected to me), I have to make my own mathematical models that run on key assumptions. And, I feel fine, because, when I get a 60% D2 dose of 200mg, it is consistent with the literature I do have access to. Also, note that the PPC of quetiapine is linear up until 200mg, which makes sense, as you are approaching the sharp flattening-off of the curve (dose v. &D2 occupied) that occurs with all AP's.

Again, if you have a better way of doing this, let me know, especially if you know of any websites with good values for the things we are talking about.

Until then, I don't really see a better way to estimate optimal dosages for a drug only using K_i,, PPC to dose, behavior ot dose to receptor occupation (linear, logarithmic, etc.) , and comparison to other AP's just to check (not to calculate, mind you).

Are you a chemist, biologist, pharmacist, doctor, or mathematician? You seem pretty knowledgeable on the stuff.

[etkearne]

Well, I'll do my finest in trying to get an algorithm going. The world of psychiatry needs some quantitative-ness (haha not a word) . I think I can do it if I have access to some of the values that Aurochs has mentioned. I might publish a paper on it (for antipsychotics) some time in the next semester, so I can probably get the Math Dept. to pay for my access to the medical vaults as well as possibly meeting with some psychiatrists.

I already have a good algorithm that works only with K_i values in selecting an optimal AP, but like we have been discussing, the dosing thing is the next step, and is much harder. Even though I complain about school, doing my own research is actually relaxing to me, so don't worry .

U-Del has a lot of good bio-math professors, too, so maybe one of them could answer some of these questions. I'll see what I can find out once this stupid Boot Camp thing is over.

[etkearne]

Check this out! You can take all the quetiapine your heart desires and you won't reach that 60% value. That is because of the hit and run effect I mentioned. I would love to quantify a relationship between time spent at the receptor and actual effectiveness.

[AnneMarie]

Are you saying that 200mg of Seroquel (or thereabouts) is optimal daily dosing for psychosis?

[etkearne]

Are you saying that 200mg of Seroquel (or thereabouts) is optimal daily dosing for psychosis?

Not at all. I am saying (more of an educated hypothesis) that 200mg of Seroquel (b.i.d. mind you- we want to keep a relatively stable plasma concentration) is a good place to start to obtain noticeable antipsychotic effects, comparable to saying 7.5mg olanzapine is the bare-bones for stopping psychosis- that value needed not been calculated. There is a graph with D2 blockade vs. dose for olanzapine, but not one for quetiapine (taking into account the quick block effect). All I have found is the relatively crappy graph I posted, which clearly took stock of the D2 blockade pretty long after administration of the drug. It plain wouldn't work if that graph was true.

Let me work up some better numbers tonight and I'll present what I have tomorrow before noon (I have off!!!).

[AnneMarie]

Are you saying that 200mg of Seroquel (or thereabouts) is optimal daily dosing for psychosis?

Not at all. I am saying (more of an educated hypothesis) that 200mg of Seroquel (b.i.d. mind you- we want to keep a relatively stable plasma concentration) is a good place to start to obtain noticeable antipsychotic effects, comparable to saying 7.5mg olanzapine is the bare-bones for stopping psychosis- that value needed not been calculated. There is a graph with D2 blockade vs. dose for olanzapine, but not one for quetiapine (taking into account the quick block effect). All I have found is the relatively crappy graph I posted, which clearly took stock of the D2 blockade pretty long after administration of the drug. It plain wouldn't work if that graph was true.

Let me work up some better numbers tonight and I'll present what I have tomorrow before noon (I have off!!!).

If you are saying 400mg/day, then search PubMed. Much work has already been done. That's the commonly considered lower end for psychosis. That holds anecdotally, as well. This is not news.

[Aurochs]

The only reliable algorithm for determining optimal dose is trial and error. The brain is simply too complex, and our knowledge of it too incomplete, to model it mathematically with any precision.

I probably don't have any more literature access than you do. (Side note: I'm surprised that a grad student doesn't have better literature access...)The Psychoactive Drug Screening Program maintains the Ki Database, which is a listing of K_i values for just about every drug produced since 1950 pulled from published research and their own labs. NCBI's PubChem database has a lot of data on structure, bioassay results, and predicted logP (a measure of lipophilicity; higher values mean the molecule diffuses across both the intestinal lining and the BBB more easily). DrugBank is a nice quick reference for a lot of things (plasma half-life, logP, chemical data, links to other databases). These all link back to PubMed, and together they have most of the data that I use.

Because lipophilicity isn't the only factor determining how much of a drug is in the brain, the best data you could get on that is a measure of the drug's concentration in cerebrospinal fluid. Unfortunately, human data for that isn't easy to come across because few people will consent to a spinal tap for research purposes. Note that a drug may have a different half-life in the brain then it does in plasma, because lipophilic compounds that have diffused into the brain (and aren't being actively removed) will preferentially stay there.

[SashaSue]

The only reliable algorithm for determining optimal dose is trial and error. The brain is simply too complex, and our knowledge of it too incomplete, to model it mathematically with any precision.

I probably don't have any more literature access than you do. (Side note: I'm surprised that a grad student doesn't have better literature access...)The Psychoactive Drug Screening Program maintains the Ki Database, which is a listing of K_i values for just about every drug produced since 1950 pulled from published research and their own labs. NCBI's PubChem database has a lot of data on structure, bioassay results, and predicted logP (a measure of lipophilicity; higher values mean the molecule diffuses across both the intestinal lining and the BBB more easily). DrugBank is a nice quick reference for a lot of things (plasma half-life, logP, chemical data, links to other databases). These all link back to PubMed, and together they have most of the data that I use.

Because lipophilicity isn't the only factor determining how much of a drug is in the brain, the best data you could get on that is a measure of the drug's concentration in cerebrospinal fluid. Unfortunately, human data for that isn't easy to come across because few people will consent to a spinal tap for research purposes. Note that a drug may have a different half-life in the brain then it does in plasma, because lipophilic compounds that have diffused into the brain (and aren't being actively removed) will preferentially stay there.

Given that we only kind of sort of think we know how these meds work, and given the variation in response from one person to the next, it seems kind of impossible to come up with a valid algorithm for figuring dosage out. Which has me wondering why a lit review of seroquel studies might not be a better use of one's time?

FWIW, BID dosing of seroquel was not sustainable for me, because of the sedation. Neither was the XR formulation. It didn't help me fall asleep at night, but it made it impossible for me to wake up ever. So I take it all at once, and it works well for me that way.

[Velvet Elvis]

FWIW, BID dosing of seroquel was not sustainable for me, because of the sedation. Neither was the XR formulation. It didn't help me fall asleep at night, but it made it impossible for me to wake up ever. So I take it all at once, and it works well for me that way.

The PDR, PI sheets, etc recommend taking it 3x a day. Anything else is off label.

It really shouldn't work at all taking it once a day.

[etkearne]

The only reliable algorithm for determining optimal dose is trial and error. The brain is simply too complex, and our knowledge of it too incomplete, to model it mathematically with any precision.

I probably don't have any more literature access than you do. (Side note: I'm surprised that a grad student doesn't have better literature access...)The Psychoactive Drug Screening Program maintains the Ki Database, which is a listing of K_i values for just about every drug produced since 1950 pulled from published research and their own labs. NCBI's PubChem database has a lot of data on structure, bioassay results, and predicted logP (a measure of lipophilicity; higher values mean the molecule diffuses across both the intestinal lining and the BBB more easily). DrugBank is a nice quick reference for a lot of things (plasma half-life, logP, chemical data, links to other databases). These all link back to PubMed, and together they have most of the data that I use.

Because lipophilicity isn't the only factor determining how much of a drug is in the brain, the best data you could get on that is a measure of the drug's concentration in cerebrospinal fluid. Unfortunately, human data for that isn't easy to come across because few people will consent to a spinal tap for research purposes. Note that a drug may have a different half-life in the brain then it does in plasma, because lipophilic compounds that have diffused into the brain (and aren't being actively removed) will preferentially stay there.

Yeah. Those are the records I have been citing. I'll check out more of PubChems's stuff soon. I bet I do have more access than I think, but I have been so busy with the math dept. that I have only been concerned with getting access to their publications.

I know it sounds like a lofty project, but I think an approximation is better than nothing. I hate to see people have to wait weeks for a medicine to work, that might not even be the right one for them. Heck, I have been on risperidone, olanzapine, and [kinda] ziprasidone, all great meds, and none have given the umph I need. Quetiapine seems more promising, but since I am not at that 200mg b.i.d range yet, I don't know. I can only hope! There is a pharmacology book that has more direct charts between receptor occupancy and steady-state dose. I think I am going to look into getting my hands on that, either by getting the department to buy it or through inter-library loans (UDel has no med school).

[etkearne]

So, taking Aurochs' suggestion, I tried to get into some "E-Journals" with my UDel ID. It worked for a good amount of them. So I have alot of number crunching ahead of me, but it looks like every source is confirming that 400mg/day, be it 200 bid or 150 tid (they don't make a 133.3333mg haha) is the threshold for AP potential. And I read that the blue chart I posted, indeed, is flawed since it measured D2 occupancy like 5 hours after taking the quetiapine. If you look at a PET graph from 1.5 hrs. afterwards, quetiapine behaves as expected.

I also found out that the psychopharmacology book that I want is in my library, so I think I am going to make a short trip there and pick it up (it is in General Circulation). Cool.