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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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« Pen and Paper | Main | A Solution, Courtesy of the MIT Faculty »

March 17, 2008

You Get What You Pay For?

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Posted by Derek

I'm a bit under the weather today, so this one will be short. Since we were talking about CNS drugs and clinical trials the other day, I thought I'd mention this article from Neuropsychopharmacology.

The authors compare reported trials of first- and second-generation antipsychotics, looking to see if potentially biasing factors have skewed the results. One (perhaps surprising) result is that the authors couldn't confirm that the newer drugs necessarily work better through showing fewer extrapyramidal side effects (those are the muscle and coordination problems seen with many drugs in this class). While they may well show fewer EPS problems, that doesn't seem to be related to their efficacy.

Something of a relief is that the efficacy of the various drugs didn't seem to be related to whether or not the drug industry sponsored the trials involved. Given the publication bias of submitting favorable results (and given the obvious commercial interests involved), that's perhaps surprising. But it's welcome data to bring up the next time someone e-mails me about the eeevil Pharma companies and their bought-and-paid-for studies. I don't get a steady stream of that stuff, fortunately, but it still shows up often enough.

I still keep an occasional eye on the antipsychotic drugs, since that was the first therapeutic area I ever worked in when I joined the industry. The project came to a bad end, which was probably a good thing for my professional development. We took the drug into Phase I, gave substantial doses to normal volunteers, and rejoiced when it did nothing to them whatsoever. Then the compound went into Phase II and into real schizophrenics, and it did nothing whatsoever to them either, sad to say. And so it goes in CNS drug development. I don't think that study was ever published; if it had been it would have presumably made the correlation between industry sponsorship and efficacy even less likely. . .

Comments (3) + TrackBacks (0) | Category: Clinical Trials | The Central Nervous System


1. sroy on March 17, 2008 4:10 PM writes...

This largely confirms what has been privately acknowledged by some psychiatrists for a few years now- that the biggest advantage of second generation anti-psychotics is their reduced EPS and other autonomic effects (better receptor selectivity).

Big pharma might yet screw this up by trying to get the FDA to approve these drugs for depression and senile dementia (esp. Zyprexa and Risperidal). There are just a few situations where these drugs add to the effects of anti-depressants - namely severe OCD and PTSD.

Unfortunately these drugs are already widely used in residential group homes for troubled teens, people with brain damage and assisted living facilities without any sound medical reason - "just to keep them quiet and compliant". Even worser is their indiscriminate use in "difficult kids" by over enthusiastic doctors. While a few of the above mentioned categories of patients might benefit from such drugs, the vast majority do not.

It is these off-label uses that might someday spark the worst backlash for this category of drugs.

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2. Gaudisso on March 18, 2008 4:11 PM writes...

I believe metabotropic glutamate receptor agonists and antagonists will be a major breakthrough for the management of schizophrenia and other neurodegenerative disorders. LY2140023, a prodrug of LY404039, is a selective Group II (mGluR2 and mGluR3) metabotropic glutamate receptor agonist with no significant affinity for dopamine receptors, thus potentially avoiding the side-effects of currently used drugs like olanzapine (Zyprexa). Manipulation of AMPA and NMDA receptors will be the next great breakthrough in neuropharmacology.

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3. sjb on March 19, 2008 7:50 AM writes...


Tying two threads together (also see "Pen and paper"), Lilly are up to number LY2140023 of registered compounds that are in the wild - it was only about 10 years ago that they first made LY393558.

Sorry for the hijack, we now return to your scheduled programme

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