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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: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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November 19, 2007

Depressing Figures for Acomplia

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Posted by Derek

Back in 2005, I worried about taking a new drug to market that had a completely new central nervous system mechanism: Acomplia (rimonabant). CNS makes me nervous. I used to work in the area, and I have a healthy respect for how little we know about it. So when you come in with something new, you have to be worried about what's going to happen, and whether your clinical trials are going to be enough to tell you about it.

And sure enough, the long, long delay at the FDA for the drug, which was (in theory) supposed to be approved in the first half of 2006, turned out to hinge on CNS side effects, among them "suicidal ideation". Now a meta-analysis has come out in The Lancet which suggests that patients taking the drug in Europe (one of the few places you can take it) have a much higher risk of depression.

You have to be careful with meta-analyses. But this one's noteworthy because, as the authors point out, depressed mood was an exclusionary factor for the studies concerned. Yet even after winnowing out those patients, the study patients seem to have been 2.5 times as likely to drop out of the trials due to depression as compared to the placebo groups. The studies totaled 2503 patients on the drug, and 1602 in the placebo groups. Depression showed up in 74 and 22 cases in those groups, respectively, which does seem to be a real effect, especially when you start by excluding anyone who seems depressed.

Compare that with the Avandia meta-analysis that has made much so much news (and come close to sinking the drug completely). Out of 14,000 patients, that one had 86 cardiac events in the treatment groups and 72 in the controls, and this in a population with underlying cardiovascular trouble. Depression is not as serious an outcome as a heart attack, to be sure, but it's nothing you'd sign up for, either. Sanofi-Aventis should stop being upset that they haven't gotten the drug on the market here, and start being glad that the lawyers here didn't get a chance to strip a few billion dollars off of them.

Comments (6) + TrackBacks (0) | Category: Diabetes and Obesity


COMMENTS

1. Timothy Leary, Ph.D., RIP on November 19, 2007 10:21 AM writes...

So you have a pill that might make you depressed. Well, I have a pill that will certainly make you happy. So why don't we put them together like chocolate and peanut butter, eh?

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2. emjeff on November 19, 2007 10:41 AM writes...

A relative risk of 2.5-fold is probably real, although I'd like to see the confidence intervals. Still, does this mean the drug should not be available to those willing to take the risk? After all, another drug that causes depressed mood (ETOH) is freely available...

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3. Morten on November 19, 2007 11:12 AM writes...

Just wanted to point out that Acomplia is a diet pill so you can reasonably demand higher safety than from something like Avandia.
But it is a meta-study so a follow-up should be designed to determine whether the effects are real or not...
On a lighter note I would have imagined that the placebo group was the more likely to get depressed since they didn't lose as much weight!

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4. JSinger on November 19, 2007 1:18 PM writes...

So you have a pill that might make you depressed. Well, I have a pill that will certainly make you happy.

Better yet, combine the cannabinoid antagonist with some medical marijuana! That should work out just fine.

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5. Smoki on November 21, 2007 5:39 AM writes...

Hmm, I'd like to see the percentage of depressed people undertaking any kind of weight-loss diet compared to those munching away freely.

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6. Jonathan on November 27, 2007 11:05 PM writes...

I said it before (http://arstechnica.com/journals/science.ars/2006/7/6/4543) I'll say it again - Accomplia/rimbonant/SR141716A was a great EDHF inhibitor, and giving it to obese people is probably a bad idea...

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