August 2, 2007

Aren't Two Antipsychotics Better Than One? The Most Important Article on Psychiatry, Part 3



Undoubtedly, your first impulse will be to punch him in the testicles, but as you know, the Kellogg-Briand pact (1928) expressly forbids this.  However, it is notably silent on the issue of voodoo/ shark attacks, which can be used with discretion.



Go back and read Parts 1 and 2.  I'll wait. 


Antipsychotics exhibit their antipsychotic effect through D2 blockade.  (1)  Got it?

Take a look at the following figure again, showing % blockade of receptors (serotonin or dopamine) as a function of dose.

So you'll observe a few things.

First, these antipsychotics will have equivalences in dosage.  If you use 10mg Zyprexa as a baseline, how much dopamine does it block?  70%.  How much Risperdal does it take to block the same amount? 3mg.  Therefore, 10mg Zyprexa = 3mg Risperdal.  If you look at the graphs for the other antipsychotics (not shown-- sheer laziness), you get the following conversion for antipsychotic effects:

10mg Zyprexa = 3mg Risperdal= 500mg Seroquel= 120mg Geodon

Interestingly, most comparator trials done-- which look at symptom responses-- show these same equivalences.  For example, ZEUS Geodon vs. Zyprexa trial: 126mg Geodon=11mg Zyprexa.  This shouldn't be surprising since THAT'S HOW THE DRUGS ARE WORKING.

Second, no drug company can claim their drug has superior efficacy, because, again, they're all working through the same mechanism. Certainly, people tolerate each drug differently, but that's not efficacy, is it? Certainly an individual might respond to one better, but you have no way of predicting that.   You simply cannot tell, by looking at someone, which drug will work and which won't. I'll show you:  which drug will work best for this guy?




It's a trick question: the correct answer is penicillin. 


The only way a drug company or study could claim to find superiority is if they don't use comparable dosages.  "We found that Risperdal 6mg was significantly more effective than 100mg of Seroquel."  Really?  Bite me.

Third, and this is really a math question:  Since there are a finite number of D2 receptors in your skull, if you are on 6mg or Risperdal-- which blocks 90% of them, and the doctor decides to augment with some Zyprexa, where's the Zyprexa going to go?  Answer: your thighs. 



 Tom recognized her instantly despite the red anonymity bar


It's not going to D2 receptors, because they're all already blocked with Risperdal.  So it's just going to go around to other receptors-- H1, a1, M1, etc-- all of which have nothing to do with bipolar or psychosis.  Issues of tolerability aside, mixing two antipychotics is no different than giving more of just one antipsychotic.

"Abiliquel"-- taking Abilify and adding Seroquel-- is sheer idiocy of such magnitude that even Eli Roth is repulsed.  The first time someone told me what Abiliquel was, the room became filled with the sounds of six guys screaming in horrific pain, and that was because I was punching them in the testicles.  Why not just give him Motrin + Advil?  Oh: "But I use it cleverly: I give 15mg of Abilify and 25mg of Seroquel.  See?"   I see.  I see that you're bleeding from the testicles.  Guess why.  You give 15mg Abilify-- that's acting as a D2 blocker.  25mg Seroquel isn't even a D2 blocker, it's an H1 blocker,  you're paying for an antipsychotic and getting Benadryl.    You say, "well, I know," (liar), "but I'm using the Abilify as an antipsychotic and Seroquel as a sedative."  But, Gwyneth, you could have gotten the exact same effect by giving Abilify and Benadryl+trazodone-- which would be cheaper, and safer; or giving simply 500mg Seroquel alone, which would have gotten you both antipsychotic effect and sedative effect, thus reducing the cost by half, etc, etc.  Remember that scene in the movie Hostel where Matthew McConaughey gets bitten by a radioactive lab rat and transforms into an immortal superhero?


Matthew McConaughey (Owen Wilson) proves there can be only one.  


No?  Do you know why?  Because you knew better than to see that celluloid atrocity.  How come you didn't know better than to prescribe two antipsychotics at once? You don't mix Zoloft and Paxil together, do you?  Haldol and Prolixin?  Seriously, do you just make crap up as you go along, or do you have pharmacological non-sequitors prepared in your Moleskine?

The same, by the way, goes for all you nutboxes who work in hospitals. If you have a patient on, say, 10,000mg of Seroquel, and he goes into an ER and gets indignant and flips a table over, and you inject him with 5mg of Haldol (90% blockade), you think that 10,000mg of Seroquel is doing him any good as an antipsychotic?  I gots news for youse all: every time you prn (emergency dose) someone with Haldol, their brain is only on Haldol.  Any other antipsychotic you give them that day is strictly a monetary gift to Big Pharma; you may as well PayPal them $180 and spare the patient the exposure. 

On second thought, you may as well PayPal me. 




1. There may come a day where a drug is invented that works through some other mechanism, maybe glutamate, but as of right now, all the available antipsychotics work through D2 blockade.  Everything else is irrelevant.  Now, these other receptors might be relevant for other effects (reducing anxiety, antidepression, etc) but let's try to focus on the specific problem and not get all Andrew Weil here.


Dear Doc,I just wa... (Below threshold)

August 4, 2007 10:40 AM | Posted by Herb: | Reply

Dear Doc,

I just wanted to take a moment to express my appreciation for some interesting information and thoughts you’ve shared. I’ve already expressed that one of your opinions I do not necessarily agree with coming from a non-medical perspective.

I also find as a support person that some of your writings indicate to me that a number of your fellow practitioners really don’t know what their doing in terms of administering drugs. Unfortunately, I can attest to that fact.

How about taking some time and changing a little direction and sharing with us your thoughts on other modalities to achieve wellness such as ECT and cingulotomy and the newer modalities TMS, VNS, DBS, MST and FEAST etc. There is a very large MDD patient population simply unresponsive, refractory and/or experiencing very short-term remission to drugs desperately seeking answers. I would be very interested.

Once again, thanks.



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thank you for the education... (Below threshold)

August 4, 2007 11:05 AM | Posted by anonymous mom: | Reply

thank you for the education... you're the wittiest teacher i've ever had.

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Bifeprunox differs from fir... (Below threshold)

August 4, 2007 4:24 PM | Posted by Stephany: | Reply

Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist.

Where do I send the rum?

Alone's response: Sigh. You're right, and I'm intoxicated. Wyeth's antipsychotic is, as you describe above, an Abilify clone. The drug I was thinking of was Wyeth's alzheimer's drug, lecozotan, which technically is a 5HT1a blocker but targets glutamate. I've changed the post. FYI, Wyeth has three different Alzheimer's drugs, two which supposedly destroy plaques.

As for rum, you'll have to just make a donation-- damn 21st Amendment. Federalist pigs.

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"I gots news for youse a... (Below threshold)

August 5, 2007 10:28 AM | Posted by Stephany: | Reply

"I gots news for youse all: every time you prn (emergency dose) someone with Haldol, their brain is only on Haldol. Any other antipsychotic you give them that day is strictly a monetary gift to Big Pharma; you may as well PayPal them $180 and spare the patient the exposure."

THIS is worth a case of rum.

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I read Haloperidol causes b... (Below threshold)

August 10, 2007 11:06 PM | Posted by mark p.s.: | Reply

I read Haloperidol causes brain shrinkage compared to
Olanzapine, whats up with that?

Haloperidol, not Olanzapine, Linked With Brain Shrinkage in Schizophrenia: Presented at SFN

By Roberta Friedman, PhD

NEW ORLEANS, LA -- November 11, 2003 -- Haloperidol may exacerbate the shrinking of the brain that scientists are beginning to link with schizophrenia. Findings of a multi-center study comparing first- and second-generation treatment for schizophrenia were announced here November 9th at Neuroscience 2003, the Society for Neuroscience 33rd Annual Meeting.

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Speechless with laughter, t... (Below threshold)

August 10, 2007 11:19 PM | Posted by TickledPink: | Reply

Speechless with laughter, thus no comment. :-)

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Would you think that (Haldo... (Below threshold)

August 13, 2007 12:49 AM | Posted by River: | Reply

Would you think that (Haldol + citalopram + Benadryl) is equal to Zyprexa or Risperdal? Those three medications combined are cheaper than the equivalent of Zyprexa or Risperdal. I know that you don't like polypharmacy, but doesn't this make sense from a cost/benefits perspective?

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Aw, you picked on the poor,... (Below threshold)

August 13, 2007 6:50 AM | Posted by Douglas Cootey: | Reply

Aw, you picked on the poor, goth child. Don't you realize he's already on anti-depressants?

Irreverent as usual, and just as insightful. Thanks for posting this.

Douglas Cootey
The Splintered Mind

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WTF? so you mean I am basic... (Below threshold)

August 14, 2007 1:20 PM | Posted by katielou82: | Reply

WTF? so you mean I am basicaly taking an antihistamine right now? (I'm on 100-150mg of Seroquel at night, depnds on how the 300mg cookie crumbles)

Well at least I know I can get off the stuff easier by just switching to benadryl at this point.

Oh and this info has helped me realize that my gut intuition that it is was the effects on Noradrenaline receptors is what was helping me was right on the money. As going up to the dosage of Seroquel that works on dopamine turned me into a zombie, and going down to where I am now does nothing for my anxiety issues, just helps me sleep at night, but being in the 300mg range did wonders for me.... well my hunch was right.

I'm off to find out more about just how Seroquel effects noradrenaline in the brain and to find a medicine that can do the same without all the damn histamine side effects, etc.

Thanks for this info.

If only most psychiatrists would tell you this stuff. I would have known months ago what sort of medication I need to try to replace the Seroquel with and neurotransmitter system it is I am trying to target.

Why do Pdocs not tell people this stuff? do they think we are too stupid to understand? Or do they themselves have no clue about it?

Alone's response: 150mg Seroquel is likely an H1 and alpha 1 blocker, so basically an antihistamine and prazosin (Hytrin) as a metaphor. 300mg Seroquel works for you, huh? Wait, a post is coming...

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Don't most people find sero... (Below threshold)

August 19, 2007 5:36 AM | Posted by Velvet Elvis: | Reply

Don't most people find seroquel more sedating at lower doses than at higher ones? I'd always assumed that it must have enough of an effect on NA at higher does to counter at least some of the sedation.

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Ok, scratch that last comme... (Below threshold)

August 19, 2007 6:07 AM | Posted by Velvet Elvis: | Reply

Ok, scratch that last comment. I read this series out of order. I'll just site here and be flummoxed for a bit.

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Case of rum vs. Federalist ... (Below threshold)

November 1, 2007 9:26 PM | Posted by Stephany: | Reply

Case of rum vs. Federalist pigs: now that a psychiatrist has placed my 19 year old on 2 antipsychotics, [Clozaril and Abilify--fffuuu--]it's on my blog, if ya want to answer there, go for it.

Before I do, you may want to screen my answer, if you like it, I'm coming over: one of the only times it makes sense to put two antipsychotics on together is when one of them is Clozaril and the other is Seroquel or abilify. The reason is that Clozaril is a major step-- if you "fail" Clozaril, there isn't much left to try. So you don't want to get rid of it. So you supplement it. However, any other antipsychotic you add will comepte with it for dopamine sites and reduce it's efficacy-- except Seroquel, which is similar in affinity to Clozaril; or Abilify, which has the different mechanism.

Why add two? One major reason is that Clozari has a lot of major side effects. So if you need 600mg to get better, perhaps you can reduce it to 400, and add 200 of Seroquel? Or 15 of abilify? Etc, etc.

Theory aside, however-- and of course I don't know your son, the situation ,etc-- my own personal practice, if a person has been through the medication rigmarole, is to stop them all (or as many as possible) and see who the person "is." People change, as they age, as things happen to them, and--yes-- medications permanently alter them. Who he was at 16, emotionally and chemically, may be very different than he is now at 19 after X medications and life events, etc. Sometimes it's worth starting over, as if there is no diagnosis, no past psych history, etc. Certainly I am not at all suggesting you do this yourself, I'm more expressing an idea that often the person is submerged beneath the diagnosis. That said, I feel for you, I can't imagine anything worse than being a parent and unable to help your child. Other than God and electricity, I don't fear anything else.

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My mother has Alzheimer and... (Below threshold)

November 9, 2007 7:20 PM | Posted by Vee Morales: | Reply

My mother has Alzheimer and has been taking Lecozatan via a study. She is also taking Zoloft and Respidal. The study has now ended and we don't know what to do because we believe the Lecozatan was truly helping. What to do?? Thanks for any help.

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If anybody is interested in... (Below threshold)

March 11, 2008 3:43 AM | Posted by Anonymous: | Reply

If anybody is interested in further details on SGA affinities for receptor subtypes, table 1 in paper has all the gory details:

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I found this topic very use... (Below threshold)

February 4, 2009 12:23 PM | Posted by Kimber: | Reply

I found this topic very useful, where were you when my daughter desperatly needed help??? Do you make house calls? lol

The reason for my reply is to address the above where someone states that Haldol causes brain shrinkage but the "new antipsychotics do not".... guess what, you're wrong...want proof take a look at my daughters brain MRI's, that will be all thr proof you need.

It's sad really, my daughter was not diagnosed properly, because she was a girl..."couldn't possibly be Autism, that's a boy's disorder", so they pile on the wrong dx's, add the medications, cause permanent brain damage and no matter how many medical tests ie: genetic's, metabolic testing etc... can not find a medical reason for this atrophy they still say it's not the drugs... I have to wonder, is it a lack of education on the doctors part or is it simply they choose to ignore so they can continue to collect their paychecks?

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You seem to be missing some... (Below threshold)

May 5, 2009 6:34 AM | Posted by NiroZ: | Reply

You seem to be missing something. If you gave someone zyprexia and seroquel, both at dosages that cover 70% of the d2 receptors, surely there would be some seroquel which would cover some d2 receptors that the zyprexia didn't cover, and vice versa.

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i was taking 160 mg nightly... (Below threshold)

April 6, 2010 9:48 PM | Posted by George: | Reply

i was taking 160 mg nightly of geodon. Is this dangerous? Can it cause damage?

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Okay, it is 1:41 a.m. and I... (Below threshold)

April 19, 2010 2:47 AM | Posted by Biwhat?: | Reply

Okay, it is 1:41 a.m. and I am on my 3rd psychosis drug went through serquoel xr, respera whatever, now abilify, cannoto even finish a script because my blood pressure is so high. Not going to die from my on demons will die from drug industries. Just descided to take a benadryl to help me sleep when I googled this website for benadryl. Totally agree. I am over this med for this and now I am on 3 more for bloodpressure problems, I go to the gym, never had heart problems before until I was determined to be bipoloar, whatever..dont think so, just bispouse. and a little depressed. Now real discouraged with these damn drugs.

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You think Abiliquel is craz... (Below threshold)

August 28, 2010 9:14 AM | Posted by Anon: | Reply

You think Abiliquel is crazy? How 'bout what I'm on - Zyprexaquel?

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I take zyprexa and oxycodon... (Below threshold)

November 3, 2010 10:50 PM | Posted by Chue: | Reply

I take zyprexa and oxycodone.

The zyprexa keeps me from going ape (actually more like "monkey", i used to fling poo in the psych ward).

The 3x 80mg oxocodone daily is pretty much a mood stabilizer =)

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February 21, 2011 1:19 AM | Posted by Generic Viagra: | Reply

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My system is so very sensit... (Below threshold)

March 20, 2011 12:32 PM | Posted by two polar two: | Reply

My system is so very sensitive to meds I don't need much of any of them...even aspirin! I tried abilify for anxiety, irritability and rapid cycling. I took 4mg for almost a month and got dystonia, weaned off in a few days and side effect went away. Began Zyprexa at 2.5mg and after 2 nights of it I feel back to normal! Yeah! However, abilify has 75 hour half wouldn't that mean that the abilify and zyprexa are working well together or that the abilify at a much lower dose might do the trick.

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Hi, My son has aspergers an... (Below threshold)

March 24, 2011 8:40 AM | Posted by Georgiana: | Reply

Hi, My son has aspergers and schizophrenia, and adhd.
He was on clonindine origianlly before they understood the nature of his problems...they just thought he couldn't sleep (He barely slept since he was 3 years old) and the clonindine seemed to make him totally crazy. He went from a child who didn't sleep and cried and wailed all the time to a child who did all the aforementioned stuff and rolled around on the floor, growled, told me he wanted me to die etc...then he was added seroquel...and then was a child who again both of the aforementioned things but then cursed to the point of looking like tourettes, wanting to kill us, hit us, abused us, and burn our house down. He then went to the hospital again and was put on geodon, clonindine, guanfasine, vyvance and another drug to help with tics, name slips my mind... It seemed to help but hyped him up a little (160 mg). The insurance wouldn't pay for it so he was switched to abilify (10 mg samples), because dr wanted him to just go without any medication until geodon issue was worked out but I insisted that my son is too crazy for that thinking. And Abilify worked awesome for a week and then he went bezerk and almost killed us forward to two weeks later, pfizer pays for Geodon. son gets geodon and it hypes him up, he puts his hand thru glass and walks down to neighbors house, goes in barn and steals 2 week old puppy. Crazy stuff. Anyway, I don't know where to go from here. speaking of mixing drugs...Can geodon and abilify be mixed?

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"My son has asper... (Below threshold)

March 24, 2011 4:09 PM | Posted, in reply to Georgiana's comment, by DOB: | Reply

"My son has aspergers and schizophrenia, and adhd."

All that in one person? Is that even possible?

Were these diagnosed all at once by the same practitioner or did different ones have different diagnoses?

What kinds of practitioner(s)-- psychiatrist, psychologist, pediatrician, or what?

How old was he when he when he was first diagnosed and how old is he now?

And what kind of schizophrenia? Paranoid, "hebephrenic," what? There are several different kinds of schizophrenia, so different that some experts think they're several different diseases/syndromes.

Does he have any other intellectual challenges (low IQ, slowness of learning)?

I'm just an interested amateur who's accumulated a few diagnoses over the decades myself and done a bit of reading in the field, and I'm frankly astounded that one person can have aspergers AND schizophrenia AND adhd.

Hell, from what you said of him I'm surprised Bipolar disorder wasn't on the list. He seems to have a lot of energy.

I'm asking all this because my different diagnoses have come from different psychiatrists at different times, even times when I was sure I felt, thought and I acted like "my usual self." Some would call me paranoid schizophrenic, some Bipolar, some Borderline, etc. A few also told me that diagnosis was not an exact science and it's mainly good to get the insurance companies to pay; even so I've never been diagnoses as Bipolar AND Schizophrenic by the same shrink, not even at different times. (Though I've been called Bipolar AND Borderline, axes I and II.)

I'm also curious about how you knew he was actually taking his medication -- did you check his mouth to make sure he swallowed? And what dosages? It seems to me that the "standard" doses of any three antipsychotics taken together would knock out anybody smaller than an elephant.

Does he "act out" most of every single day or just sometimes on some days when he's particularly upset? From the description you gave it sounds like the poor kid would be spending most of his time locked up and in restraints. (I say "poor kid" because I doubt his life can be a happy one; I'm glad I'm not him.)

And last but not least, are you really a real mother or a teenager trolling the blog? "Aspergers and schizophrenia, and adhd" sounds like what an 11th grader might call somebody she's not fond of.

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I wonder how one would act ... (Below threshold)

January 3, 2012 6:26 PM | Posted by Larissa: | Reply

I wonder how one would act if 100% of your dopamine receptors and 100% of your serotonin receptors were effectively blocked. Probably the goal of most drug companies and psychiatrists if given the choice or legality to do. You'd probably just be a living, breathing vegetable incapable of emotions, feelings, and cognitive thinking abilities, oh wait I've already reached that point.

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Seroquel,Risperal reproache... (Below threshold)

January 11, 2012 1:47 PM | Posted by Daniel Haszard: | Reply

Seroquel,Risperal reproached.
Same saga here as Eli Lilly Zyprexa.
Lilly made $41 Billion on Zyprexa using *off Label" push promotions.
The AG of more than one state talked of using the R.I.C.O act on them.
Zyprexa was hailed as *the most successful drug in the history of neuroscience*.
Wonder why?
Risperdal,Zyprexa.Seroquel are glorified Thorazine at ten times the price.
-- Daniel Haszard Zyprexa victim activist.
FMI Google--Haszard Zyprexa
*Tell the truth don't be afraid*

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Has anyone tried abilify an... (Below threshold)

February 24, 2012 9:10 PM | Posted by Anonymous: | Reply

Has anyone tried abilify and trileptal. It worked for my childs rages very well.

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Oponions sought on doctors ... (Below threshold)

May 15, 2012 10:07 PM | Posted by Mother: | Reply

Oponions sought on doctors decision today to add injectable prolixin to her already 20mg zprexa and Vistaril 50mg as needed for anxiety. She is currently bi-polar mixed, experiencing depression psychosis....but not when she sleeps at night. She has ALL the bad side effects of Zyprexa except one....she has not yet experienced sudden death!

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Are you a doctor?I m... (Below threshold)

December 19, 2012 8:11 PM | Posted by Fernando: | Reply

Are you a doctor?
I must say you are not tottaly wrong, but not tottaly wright aswell. You must think that "affinity" is like an magnectic force pushing sand from different places. It does go more to where is pushing harder yes, but the brain is composed by different regions and different neurons, whethever this "sands" go through accumulates in different spectrums. Even if ones take 25 mg of seroquel, probably a minuscle portion of that "beach" will bind to D2. But would be insignificant. I believe you understand and thinks the same way as I am telling but you prefer to "simplify" it for people to understand it easily. Your thoughts are wright in practice, but this is a very deep cience and no one knows the exact mecanism of which drugs use. thank.

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also, dopamine and serotoni... (Below threshold)

December 19, 2012 8:16 PM | Posted by Fernando: | Reply

also, dopamine and serotonin aren't everything on psychosis and depression, respectly.

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Fecal incontinence is a dis... (Below threshold)

August 11, 2013 4:13 PM | Posted, in reply to Chue's comment, by Ok: | Reply

Fecal incontinence is a disturbing occurrence to most patients. For instance,
severely psychotic, schizophrenic patients rarely soil themselves. Alzheimer’s
patients will make significant efforts to prevent self-soiling and episodes of
incontinence often produce significant distress in even the most demented

smearing in a borderline IQ or mildly retarded in strongly suggestive of
manipulative behavior.

source -

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The Dr wAnts to add abilify... (Below threshold)

September 29, 2013 8:21 PM | Posted by Anonymous: | Reply

The Dr wAnts to add abilify to the haldol he is tAking. Is this safe? He is totally stable but does still hear voices

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hi all.great post.i love di... (Below threshold)

April 10, 2014 6:49 PM | Posted by boogie1: | Reply

hi all.great post.i love discussing psyche meds.i personally take chlorpromazine 50mg and 3mg risperidone and ive found they've raised my cholesterol quite abit,but thats all the side effects ive bipolar and these two kick the shit out of my D receptors.i found seroquel and abilify pretty useless on dopamine.keep the comments coming guys.

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This stuff has turned out t... (Below threshold)

April 25, 2014 8:41 PM | Posted by Altostrata: | Reply

This stuff has turned out to be invaluable in understanding how to get people off these hellish concoctions, see

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