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Clozapine: The Best Antipsychotic?


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#1 In_Remission_peterwait

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Posted 12 September 2008 - 09:42 PM

Is it true that clozapine is the best antipsychotic? And if so what makes it the best?

Edited by peterwait, 12 September 2008 - 09:46 PM.




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#2 Simba Cub

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Posted 13 September 2008 - 12:33 PM

I vote for Clozapine. It was the only antipsychotic I seemed to react to and seemed to be the best bet, with me needing an antipsychotic QUCIK etc.

I don't mind the blood tests now that they're monthly, but for the first few months (when they're weekly) they can be very annoying.



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#3 sorrel

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Posted 13 September 2008 - 04:48 PM

Clozapine is generally considered the most effective antipsychotic for both positive and negative symptoms, and is considered to be the most effective for psychosis that has not responded to other drugs. It also is the most effective AP as a mood stabilizer. However the side effects are nasty, ranging from potentially fatal (agranulocytosis) to highly annoying (drooling).
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#4 Simba Cub

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Posted 13 September 2008 - 04:51 PM

I also believe that the older "typical" antipsychotics tend to pack more wallop than the newer, atypical drugs.



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#5 diagnosed

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Posted 15 September 2008 - 02:43 AM

a agree w Jook
i was on Clozapine for years, but had to stop because i coulnd stand the knockouts (sedativeness) anymore, it messed around with my career
being on Risperdal now, im not sorry i must say
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#6 Jerod Poore

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Posted 18 September 2008 - 01:00 PM

Is it true that clozapine is the best antipsychotic? And if so what makes it the best?


Define "best."
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#7 Serpens

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Posted 18 September 2008 - 07:08 PM

From a human pharmacotherapy course about a year ago, and this is talking in terms of just raw schizophrenia, nothing else. Take any random antipsychotic, new, old, doesn't matter, and throw it at a schizophrenic. 1/3rd of them will get better dramatically, 1/3rd sorta get a little better but not much, and a 1/3rd just continue to get worse. The doctor running the class has been treating schizophrenics for about 35 years. Meaning if you pick a random group of schizophrenics, and a random antipsychotic, they'll sort themselves out like that. Not that the ones who don't improve won't get better on a different drug, but when you're selecting an antipsychotic, you're basically choosing side effects. The exception, he said, was clozapine. Take that random group of schizos, put them on clozapine, and around 60% of them will improve dramatically. Mentioned back that back in the 70s, they pulled clozapine off the market, but then had to bring it back, as there were schizophrenics who just did not respond to anything else.

None of that verified by me, just relating his opinion. This guy knew his crazypills like few others on earth though.
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#8 Jerod Poore

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Posted 19 September 2008 - 12:45 PM

Take any random antipsychotic, new, old, doesn't matter, and throw it at a schizophrenic. 1/3rd of them will get better dramatically, 1/3rd sorta get a little better but not much, and a 1/3rd just continue to get worse. The doctor running the class has been treating schizophrenics for about 35 years. Meaning if you pick a random group of schizophrenics, and a random antipsychotic, they'll sort themselves out like that. Not that the ones who don't improve won't get better on a different drug, but when you're selecting an antipsychotic, you're basically choosing side effects. The exception, he said, was clozapine. Take that random group of schizos, put them on clozapine, and around 60% of them will improve dramatically.


I actually believe this, as the vast majority of people with schizophrenia are treated by doctors who are paid by Medicaid, counties and charities. Usually not by choice. In any event there's rarely lots of investigation into the sort of symptoms are presenting (positive vs. negative, what sort of either or both, and is it somewhere in the schizoaffective part of the spectrum or not). Almost all patients and far too many doctors don't think about how a drug works to treat specific symptoms, they have side effects front and center in their decision trees. It's not the way it should be, but it's the way it is in the real world.

The one thing that doesn't ring true for me is Zyprexa not being in the equation. Zyprexa is damn close to clozapine in its mechanisms of action. I'd expect at least half would see dramatic improvement and another big chunk getting somewhat better.
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#9 Serpens

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Posted 20 September 2008 - 11:51 AM

The one thing that doesn't ring true for me is Zyprexa not being in the equation. Zyprexa is damn close to clozapine in its mechanisms of action. I'd expect at least half would see dramatic improvement and another big chunk getting somewhat better.


Actually, he mentioned this too. Zyprexa was an attempt to create a clozapine-like drug and try to come up with a version of it that didn't cause agranulocytosis, as that's the main problem with using the drug. He said it really didn't seem to have worked. They got the sedative potency and weight gain, but not it's stellar success rate or agranulocytosis. His thought was that it was the alteration of the tricyclic ring structure - clozapine has a sex membered aromatic ring with no substituents. Zyprexa on the other hand, has a five membered aromatic ring with a sulfur in it and a methyl group sticking out. Since the tricyclic ring is the 'key' to GPCRs, he figured that clozapine was binding somewhere that we weren't thinking of or studying, and the alteration in Zyprexa's ring structure was significant enough to inhibit its action at this point, without significant alterations to its D2/5HT binding efficiency. He's also one of the folks that thinks the Dopamine and Glutamate models of schizophrenia come nowhere near to explaining everything either together or individually.

And you're absolutely right Jerod. Schizos go into the hospital, get put on meds and come out, and go off meds. One of the main selection criteria seems to be remission and something that they'll actually -stay- on. And part of compliance is side effects. Oh. And price. When you're dealing with medicaid, medical and other public insurance issues, price is a BIG issue. As we all know, up until this year all the AAPs were still on patent, and state insurance doesn't like coughing up 700 bucks a month for schizopills any more than your average citizen does. Hooray generic risperdal.
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#10 Jerod Poore

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Posted 26 September 2008 - 01:05 PM

I missed this response.

The one thing that doesn't ring true for me is Zyprexa not being in the equation. Zyprexa is damn close to clozapine in its mechanisms of action. I'd expect at least half would see dramatic improvement and another big chunk getting somewhat better.


Actually, he mentioned this too. Zyprexa was an attempt to create a clozapine-like drug and try to come up with a version of it that didn't cause agranulocytosis, as that's the main problem with using the drug. He said it really didn't seem to have worked. They got the sedative potency and weight gain, but not it's stellar success rate or agranulocytosis. His thought was that it was the alteration of the tricyclic ring structure - clozapine has a sex membered aromatic ring with no substituents.


Best typo today!

Zyprexa on the other hand, has a five membered aromatic ring with a sulfur in it and a methyl group sticking out. Since the tricyclic ring is the 'key' to GPCRs, he figured that clozapine was binding somewhere that we weren't thinking of or studying, and the alteration in Zyprexa's ring structure was significant enough to inhibit its action at this point, without significant alterations to its D2/5HT binding efficiency.


Most of the crazy biochemical moon talk is completely over my head. Molecular shapes = important. E.g. aromatic vs. non-aromatic anticonvulsants in anticonvulsant hypersensitivity syndrome. That's as far as my understand is right now.

Clozapine working somewhere no one is looking: sure. Why not? There's grant money there.

He's also one of the folks that thinks the Dopamine and Glutamate models of schizophrenia come nowhere near to explaining everything either together or individually.


I'll go along with that one. As there's no money in schizophrenia the advances in understanding treatment will come slowly. It's a good thing they've found so many similarities between bipolar and schizophrenia. I'm more than happy to be associated with schizophrenics if it means better treatment options for everyone.
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Current meds: lamotrigine 300mg, topiramate 325mg, buspirone 60mg, protriptyline 60mg, EPA 600mg, methylphenidate 5-10mg, lorazepam 1mg PRN
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