thelastpsychiatrist.com - CATIE: Sigh. Adnotated.

1. You know, if you're going to be rigorous about BID dosing schedules because the FDA requires it, why so liberal with total dosing for Zyprexa? A mean dose of Zyprexa is 20.8 is way (150%) above FDA guidelines. For comparison, that would have meant dosing Geodon at 240mg, Seroquel at 1000mg, and Risperdal at 6mg. BTW: a mean of 20.8mg means that a lot of people were dosed with MORE than 20.8mg (max=30mg).
2. The miracle here isn't that Zyprexa won, but that Zyprexa 20mg barely won against Geodon 114mg.
3. Why Trilafon (perphenazine)?ⁱ Originally you thought all conventionals were the same; so why not Haldol?ⁱⁱ Or Mellaril?ⁱⁱⁱ You say it's because it had lower rates of EPS^iv and TD^v, which is fine, but then why exclude TD patients from that arm?

4. So you excluded patients with tardive dyskinesia from the perphenazine group (fine) but then had the nerve to say people tolerated it as well as other meds? Do you think maybe people who have TD may have different tolerances to meds? Different EPS? Different max doses? That they're just different?^vi

5. You can't generalize from an obviously slanted "typical" arm to all other typicals. If you chose Trilafon over Haldol because of better tolerability a priori, you can't now say that "typicals" have equal tolerability to atypicals. Why not pick two typicals of differing potencies (like Mellaril and Haldol) and infer from there?

6. Do you actually believe -- does anyone believe -- that any of these patients are compliant with BID regimens? Especially with sedating meds like Seroquel?

The secret to understanding CATIE 2 is to understand that there are two CATIE 2s.^vii

CATIE2-Efficacy: People who dropped out of CATIE 1 because their med didn't work were randomized to Clozail, Zyprexa, Risperdal or Seroquel. On average, new Clozaril switches stayed on 10 months, everyone else only 3. 44% of Clozaril stayed on for the whole 18 month study; only 18% of the others completed the study.

CATIE2-Tolerability: People who dropped out of CATIE 1 because of side effects (not efficacy)^viii were randomized to Zyprexza, Risperdal, Seroquel, and Geodon (not Clozaril.) Risperdal patients stayed on for 7 months, Zyprexa for 6, Seroquel for 4 and Geodon for 3.

CATIE2-Efficacy is fair. If you fail a drug, you're likely to do better on Clozaril^ix than anything else.

CATIE2-Tolerabilty makes no sense at all. The reason Geodon was used is because it has "very different" side effects. Hmm. How? "In particular, ziprasidone [Geodon] was known not to cause weight gain." But this assumes that the intolerability of the first antipsychotic was its weight gain.^x

Most importantly is this: if a patient couldn't tolerate their first antipsychotic, how likely is it that it was effective? In other words, if it wasn't tolerable, it wasn't efficacious -- these patients could have been in CATIE2-Effectiveness study. So how did they choose?

Easy: they gave the patient the choice: Geodon or Clozaril?^xi Out of 1052, half left altogether.^xii 99 went into the Clozaril study (CATIE2-Effectiveness) and 444 went into Geodon (CATIE2-Tolerability.) Of the 444 in the Tolerability trial, 41% were actually labeled first drug non-responders. 38% were labeled as not tolerating their first drug, but of those, who knows how many were also nonresponders?

And 74% dropped out again.^xiii

If you take the 444 in the Tolerability study and divide them into two groups:

• those who left CATIE1 because of lack of efficacy: then switching to Zyprexa or Risperdal kept them on their meds longer. (Which makes no sense again: this is the same thing as the CATIE2-Effectiveness, where (except for Clozaril) there was no difference between Seroquel, Zyprexa and Risperdal.^xiv)
• those who left CATIE 1 because of lack of tolerability, then it made no difference what you switched to.

Sigh.

And what's with the blinding? In every other study with a clozapine arm, you equalize the weekly blood draws by making everyone have to submit to them. But in this case, they unblinded clozapine^xv so as not to have to subject all these people to blood sticks. Except they were subjecting them already -- they were checking blood levels.

And where was perphenazine? "[CATIE1] did not anticipate this unexpected result [that perphenazine would be as efficacious] that challenged the widely accepted (but never proven) belief that the newer atypical antipsychotic medications are better than all older antipsychotic medications" and so was not considered for CATIE2. Apart from the fact that it is simply untrue that anyone thought the atypicals were more efficacious than the typicals, it is furthermore untrue that that the authors did not "anticipate this unexpected result." In 2003^xvi, after basically doing Medline meta-analysis, they found that "not all of them were substantially different from conventionals such as perphenazine."^xvii

What's funny about these guys is how they conveniently lump all typicals together but arguing for differential effects of individual atypicals; then argue typicals are different from each other to justify picking Trilafon; and then say atypicals are different from each other ("not all of them were different") but typicals are all pretty much the same ("conventionals such as perphenazine.")^xviii

Bottom line:

The stated purpose of CATIE2 was to help clinicians decide which drug to switch to if patients a) failed their first drug; b) couldn't tolerate their first drug.^xix

The divorce rate in America is 40-50%. Say you get divorced, and a friend says, I have two women for you, Jane and Mary. If the problem with your first wife was that she didn't turn you on, you should marry Jane. If the problem with your ex was that she was annoying, you should marry Mary.

What's going to happen here is that your second marriage, to either girl, is doomed. Certainly more than the national average of 50%. How long is it going to take before your second wife doesn't turn you on either? How long before you find stuff intolerable about her? The answer is, more likely than your first marriage -- say, 75% -- because the problem isn't your wives, it's you. You've framed the question in an idiotic and arbitrary manner. You don't get married to get turned on OR to be with someone who isn't annoying. You want the marriage to have both simultaneously, and much more. These things are not separable. This is CATIE2. A meaningless dichotomy -- efficacy and tolerability are not separate, let alone opposites -- used to create a false paradigm of medication selection.^xx

1. Traditionally the "minor sedative" pumped into vagrants, junkies and other social marginals "with a history of" drug abuse. Not anymore though. [↩]
2. Decent rape drug, as it happens. [↩]
3. Thioridazine, now withdrawn but for many years widely dispensed "treatment" for cardiac eurhythmia. [↩]
4. "Extrapyramidal symptoms", currently fashionable euphemism for "frying the peripheral nervous system". [↩]
5. Tardive dyskinesia, chemically induced senility symptoms. [↩]
6. Science! Excluding selected groups from samples is where it's at! [↩]
7. This is an astute point, and obviously relevant enough to have been mightily obfuscated by the "scientists" in charge of the pile of nonsensical wank. [↩]
8. Granted this distinction lies mostly in the mind. [↩]
9. Clozapine, the fashionable drug at the time ; cheap as all get-out too, a dime or so a dose.

   Also results in bedwetting. And dementia, syncope, bone marrow supression, a whole laundry list of medical benefits. But principally bedwetting. [↩]

10. Seeing how socially useless, practically inept, objectively worthless, overfed and idle females constitute most of the population this priesthood ministers to, it does not strike an outside observer as remarkable that indeed cosmetic preoccupations would constitute the main thrust and weight gain would be first on that list. This is the hard core of people who don't do anything all day long after all. [↩]
11. The heights medical science has crested in our colonies strikes fear into the mind of man. I shall make a note to complain to my car mechanic next we meet, that upon my bringing the car in for fixing he doesn't give me a choice of parts to put in -- wouldn't it be so much better if he went "your shocks are shot, would you like to try a steering wheel hammered in place or a chunk of concrete rubble with rebar sticking out welded in ?" [↩]
12. What they muttered on their way out obviously left unrecorded by the stupid cunts involved -- though it was the only genuinely interesting material this entire idiocy ever came into contact with. CATIE should've been refurbished into an ethnofolkloric notation effort, thereby achieving some (modest) scientific notability. [↩]
13. These "drugs" prescribed by these "doctors" work almost as well as the "colleges" that spawned them all in the first place! [↩]
14. On a sample of three thumbtacks and one stray dog. [↩]
15. Which then worked out better! Proportionally! Keks. [↩]
16. Link was www.catie.unc.edu/schizophrenia/CATIE%20SZ%20primary%20analysis%20methods%20-%20Jan%2017%202005%20-%20FINAL.pdf ; admire the discreet beauty of utter retardation! [↩]
17. Yes, but they're "doctors" of the government-issued sort. They don't read (and can't spell), they simply produce "consensuses" by sitting on their ass all day long and preening at each other's nits an' headlice. [↩]
18. "Funny" is one way to describe it, using the word in the same way it is traditionally used to describe the patients -- which leads us to the unescapable conclusion that the only people who belong committed to insane asylums are the current psychiatrists. [↩]
19. While the actual purpose was to at the same time make them all equal and the same (thus satisfying the principal requirement of socialism imanent in their brainstem) and all specific and different (thus justifying the waste of time, effort and resources going from one useless poison to the other). It's a lot like the "dating" game, whereby all the dumb cunts are equal and identical but all also special and particular, and you're more than welcome to waste howevermany years in the yarnball. [↩]
20. And, recursively, a man who is intelligent enough to notice the "dating" parallel, but nevertheless manage to hide the real implications from his own eyes. Vorwarts! [↩]