Corcept Spins Out

The interesting thing about Corlux (mifepristone/RU-486) is that no matter how it fares in clinical trials, it is always a winner. In the latest trial, Corlux was again not effective on the primary outcome measure, which assessed the psychotic symptoms of psychotic depression. This is not surprising, since it has generally shown mediocre results, which are then spun by the company executives/academics as evidence of treatment effectiveness. Oh, and despite this being pushed as a treatment for psychotic depression, the treatment has never yielded anything resembling efficacy for depression, which strikes me as pretty odd.

Dr. Joseph Belanoff, Corcept CEO, had the following to say about the latest trial results:

While we are disappointed that the trial did not meet the primary endpoint, we are particularly encouraged to have met the important predefined threshold concentration endpoint with statistical significance," said Joseph K. Belanoff, M.D., Corcept's Chief Executive Officer. "This study confirms our previous observation that at higher plasma levels the drug candidate is able to demonstrate desired clinical effects. In particular, those patients in Study 06 who achieved a predetermined level of 1661 nanograms of CORLUX per milliliter of plasma separated from the placebo group with statistical significance.

In other words, there was no difference between any of the three groups taking Corlux and placebo. None. So it appears that they started data dredging (e.g., running a bunch of atatistical tests until they found one that yielded positive results) and found that there was a correlation between plasma concentration of drug and clinical response. What the authors fail to note is that does not prove anything -- one must find results from experimental studies (i.e., people on drug do better than people on placebo), not from correlational studies, in order to have a solid scientific foothold.

An academic, who serves on Corcept's scientific advisory board, was also willing to make a sunny statement about the findings:

Ned H. Kalin, M.D., Hedberg Professor and Chair of the Department of Psychiatry at the University of Wisconsin, said, "The correlation between plasma levels of drug and response rates found in this trial is very exciting. The results of this study show that when psychotically depressed patients achieve a threshold concentration of CORLUX in their system, a rapid and sustained clinical response is likely. This is a strong demonstration of a drug effect in an illness that is potentially devastating and difficult to treat."

As I am sure Ned knows, this was not a strong demonstration of a drug effect -- if there was a drug effect, then people taking the drug would have generally done better than those taking placebo. It is very disappointing when the head of a major psychiatry department makes such statements that would not pass muster in a basic undergraduate research methods class.

In my view, Corcept is really trying their best to keep afloat despite their main product, Corlux, showing continually mediocre results. Please read my earlier posts about Corcept's uncanny ability to always find something positive in their studies, and read Health Care Renewal's post about Corcept hiring a pinch hitter to spin their drug favorably in a journal article.

Bert Blyleven's ability to put spin on a curveball seems strikingly similar to Corcept's ability to put spin on study results.

4.83 Million Reasons to Be Conflicted

Corcept Therapeutics just got an infusion of cash. From the press release:

Corcept Therapeutics Incorporated (NASDAQ: CORT) today announced the completion of a private placement of 9,000,000 shares of its common stock at a price of $1.00 per share, pursuant to a definitive agreement entered into today with accredited investors. The investors are led by Paperboy Ventures LLC, who is currently a significant shareholder of Corcept. Sutter Hill Ventures, Alta Partners, LLP, venture capital firms that are currently significant shareholders in Corcept, and members of the Corcept Board of Directors, Joseph C. Cook, Jr., James A. Harper, David L. Mahoney, Alan F Schatzberg, M.D. and James N. Wilson, are also investors. In addition, investors in this financing round included Black Point Group, LLP, Vaughn Bryson and Daniel Bradbury.

Already a good short-term investment, as the stock is now at $1.21 a share. If you've read my prior writings about Corcept, you can see that I'm highly skeptical about it's main product, Corlux (mifepristone/RU-486), which is aiming to treat psychotic depression. Although the company has tried to spin negative findings as actually being positive, it's hard to see how a series of studies showing poor efficacy will lead to helping patients in any meaningful fashion. Might the latest influx of cash help out the Corcept insiders who hold a major stake in the company? Sure.

Conflicts of Interest: It appears that Dr. Alan Schatzberg bought 50,000 shares in the latest round of funding. It has been reported previously that Schatzberg has written quite positive comments about Corlux in journals and some have questioned whether his financial stake in the company has skewed his judgment on the topic. I want everyone to consider the following conundrum...

Schatzberg holds about 4.83 million shares of Corcept currently. So, if Corlux bombs a clinical trial, is he going to:
A. Immediately report the negative results in a press release
B. Move publishing the negative results in a scientific journal to the top of his to-do list
C. Spin the results in a very favorable fashion (or make sure that someone who writes the press release and/or scientific paper does so)
D. Just bury it entirely (probably not an option with such a small company that likely announces most if not all of its trials beforehand)

If I was in a position where I had such a large financial stake, I'd have a hell of a time doing A. or B. When large dollar amounts are at stake, it's not easy to say, "Hey, this product doesn't seem to work" and watch your stock holdings evaporate. This is why conflicts of interest are a problem.

Some academic researchers really are just in it for the money. I think they are a very small minority. I bet that most researchers who end up with big-time conflicts of interest start off thinking, "Hey, this could be a great new form of treatment for condition X." Then, hey, why not make some money while you're doing God's work, helping to heal people. We're an entrepreneurial society, so we tend to believe that people should be rewarded for having an enterprising spirit. Now, if the product turns out to not be so effective and/or to have some unpleasant side effects, then look at the predicament... Here's the conflict -- help people with condition X or help my own cash flow?

Or say I'm a doctor who makes some good money on the side giving "educational" speeches to fellow physicians about a drug, say, Zyprexa. When I find out that said drug is linked to numerous health problems, do I bring that up in my speeches, knowing fully that such discussion is likely going to get me canned from the speaking circuit?

The list of potential examples could go on for days.

Corcept: We'll Take Our Ball and Go Home

...because we can't afford the basketball court. Corcept, which has run a series of studies (1, 2) demonstrating poor efficacy of its drug Corlux (mifepristone/RU-486) in treating psychotic depression, has watched its chief financial officer resign (way to get off the sinking ship Fred!) recently. Corcept also stated in a press release that...

For the fourth quarter of 2006, Corcept reported a net loss of $3.9 million, or $0.16 per share, compared to a net loss of $5.2 million, or $0.23 per share, for the fourth quarter of 2005. For the full year 2006, the company reported a net loss of $24.9 million, or $1.09 per share. This compares to a net loss of $20.1 million, or $0.89 per share, for the full year 2005.As of December 31, 2006, Corcept had cash, cash equivalents and marketable securities of $9.5 million. The total cash used in the company's operating activities for the full year 2006 was $23.2 million. Commenting on Corcept's financial guidance for 2007, Fred Kurland, Corcept's Chief Financial Officer, stated, "Based on the currently planned timeline of our clinical development program and assuming that we are able to raise funds for intended operations, we expect that net cash used in 2007 will be between $10 million and $15 million. If we are not able to raise additional funds, we will not be able to continue operations beyond the second quarter of 2007."

Sounds like a plea of desperation to me. Anyone willing to sign up? I'll just get my checkbook out now. Corcept stock (incredibly) was once valued at over $10 per share, and now sits at 71 cents. I guess you could call this an extreme form of value investing (except for the company's lack of earnings). It appears that just issuing press releases and/or writing journal articles that spin their negative findings as positive is not working so well.

Conflicts, Bad Science, and Corlux

Recently, the watchful eyes of Charles Grassley have been peering into the bank accounts of big name psychiatrists. Melissa DelBello and Joe Biederman (1, 2) from the Wonderful World of Child Bipolar were first, and now Alan Schatzberg has been hit. Schatzberg is the Chair of Psychiatry at Stanford University. He is also the President of the American Psychiatric Association. In other words, he's kind of a big deal.

Pharmalot hits the details, but the gist is that Schatzberg is deeply involved at Corcept Therapeutics, a company for which he is chair of the scientific advisory board and holds a large amount of stock. According to Grassley, he did not disclose some of his stock sale profits or the magnitude of his multimillion dollar stock holdings in the company. Additionally, Schatzberg allegedly underreported income received from other drug companies. It appears that Schatzberg was not really required to disclose some of this information, so according to my brief review of the information, it is quite possible that he has broken no rules. Now, whether the rules need to be changed is a different story. No offense to Grassley, but I was well ahead of him on part of this story, noting in April 2007 that Schatzberg had a mega-conflict of interest going with Corcept. I also noted previously that Schatzberg was on the Zyprexa bandwagon, helping to "educate" fellow physicians about the Lilly wonder drug.

The Real Problem: But amidst all this discussion of conflicts of interest, I am afraid that we are getting a bit diverted from the main problem, that of shoddy science. It is admittedly interesting noting that Schatzberg is somehow supposed to be an independent, disinterested scientist while standing to make an absolute truckload of money if his sponsored product succeeds. But it runs deeper. While Schatzberg is a bigwig at Corcept, let's review how Corcept's main product mifepristone (RU-486; yes, the abortion pill) has done.

Mifepristone (aka Corlux) is intended to work as a treatment for psychotic depression. One main problem: It doesn't relieve depressive symptoms. In multiple trials, it has failed to demonstrate antidepressant properties. The CEO of Corcept and another member of their scientific advisory board have previously tried to spin away such inconvenient data by painting negative results as positive. To give Corcept credit, their scientists are consistent spinmeisters, seemingly always able to dredge a positive from obviously negative findings. Schatzberg has been an author on a couple Corlux-related papers that were shredded by independent analysts, who found statistical problems and overly optimistic interpretations of the study results. As the senior member of the Scientific Advisory Board, I assume that Schatzberg had some input on the other study reports that also overstated the efficacy of Corlux.

Could his millions of dollars in Corcept holdings bias Schatzberg, either subconsciously or overtly? You be the judge. But remember that this is not just about conflicts of interest -- this is about science. There is hard evidence that the research on Corlux, which is tightly linked to Schatzberg, has been misinterpreted for the sake of marketing. Conflicts of interest sometimes lead to bad science, but rather than focus just on conflicts of interest, we need to dig a layer deeper and see the poor science -- the shoddy evidence that is used as the foundation for "evidence based medicine" in many cases.

Note also that David Healy has written an interesting piece on the topic of conflicts of interest and bad science, pointing out that a larger problem is lack of access to company-owned data. Think Paxil and suicide. He concludes:

If I were employed in a company marketing department I would much prefer to have the field think that all that is wrong is that a few corrupt academics fail to declare competing interests than to have the field think that company practices that restrict access to data while still claiming the moral high ground of science are the real source of the problem.

I'd love to know what American Psychiatric Association members think about this. The news had already broken about Schatzberg overstating the efficacy of Corlux before he was elected APA president. Do APA members not care that their president has a documented record of putting product promotion before scientific evidence?

Conflicts, Bad Science, and Corlux: Part Two

The blogosphere has been abuzz with discussion of psychiatrist Alan Schatzberg's dual roles as a tycoon and an allegedly "objective scientist."  But wait... there's more.  Schatzberg is deeply involved with Corcept Therapeutics, a company that has repeatedly found that mifepristone (Corlux/RU-486) is a dud for psychotic depression.  Yet Corcept has continually attempted to spin the results as positive, in a manner that should be obvious to anyone who passed an introductory research methods or statistics course.  Schatzberg has millions of dollars in Corcept shares and should Corcept actually turn out to possess even minimal efficacy for psychotic depression, Schatzberg stands to profit quite handsomely.  

Bernard Carroll has the next chapter in this interesting saga, dealing particularly with Stanford University's claim that Schatzberg was not involved in "managing or conducting any human subjects research" using Corlux.  Such a claim is essentially saying that because of his financial connections with Corcept, Schatzberg avoided tight involvement with the studies of the drug so that he could avoid a conflict of interest.  Dr. Carroll, however, notes that it seems very likely Schatzberg was indeed involved in Corlux research.

There is reason to believe that Dr. Schatzberg had a key role in Stanford’s clinical trials of Corcept’s drug reported in 2001, 2002, and 2006. He was a co-author on all three publications, and there was no disclaimer about his role until 2006. This disclaimer is hardly credible. As Principal Investigator on the NIH grants, Dr. Schatzberg was expected to supervise the junior faculty and research staff at Stanford who recruited, assessed, and treated patients in the studies of RU 486. He was responsible for the choice of outcome measures, about which questions have been raised. He was responsible for the quality of the reported data analyses, which were, frankly, inexpert, when they were provided at all. Above all, he was responsible for the tone of the NIH-supported Stanford publications that claimed Corcept’s drug is effective.

That's just a tidbit -- there is much more to the story, and it should be read immediately at Health Care Renewal.  Keep in mind that Schatzberg is the president of the American Psychiatric Association.  You may then choose to giggle or cry -- your choice.  

Corcept: Still a Bad Investment

My pals over at Corcept continue to lose money. You may recall Corcept as the company that is trying desperately to get mifepristone (RU-486) approved to treat depression. The main problem has been that trial results have yielded little hope. The oft-cited (both on this site and in the psychiatric literature) Charles Nemeroff has a conflict of interest related to Corcept that you can read about here. Here's the latest on Corcept:

"(RTTNews) - Corcept Therapeutics Inc. (CORT | charts | news | PowerRating) reported a third quarter net loss of $6.4 million or $0.28 per share, compared to a net loss of $5.2 million or $0.23 per share in the same quarter of last year.

Analysts polled by First Call/Thomson Financial expected the company to report a loss of $0.28 per share.

For the nine months of 2006, the company reported a net loss of $21.0 million or $0.93 per share, compared to a net loss of $14.8 million or $0.66 per share in the year ago period. Collaboration revenue for the period was $221 thousand."

Link here.

New American Psychiatric Association Prez: We Want Money

In a recent speech, incoming American Psychiatric Association president Alan Schatzberg was quoted as saying:

"As the recent attacks on APA and leaders of the profession have occurred, it has struck me that some of the detractors in the press have voiced concern that some folks have earned too good a living, often by doing presentations," he said. "I have heard from colleagues and directly from one reporter asking me about one of my colleagues having too high an annual income. I can assure you these detractors would not ask the same question of a surgeon or radiologist earning 10 times the amount paid our colleagues. None of us do what we do for money. Yet, it is also time for us to realize that our members and residents have never taken vows of poverty, and the complexity of the work deserves to be recognized. We need to ask ourselves how we have contributed to our own devaluation with which others seem to resonate, and we need to reverse the course. The rewards for our dedication should not be limited to a sense of pride, but we are also entitled to be paid commensurate to the challenge.

So Schatzberg must be diving into dumpsters, begging at interstate off-ramps, and the like. Oh, wait a minute. This is the same Alan Schatzberg who in 2007 owned close to 5 million shares of Corcept (which translates into roughly 5 million dollars). I have no idea how many shares he owns currently. Corcept, in case you missed it, has shown its drug mifepristone (aka RU-486: "The Abortion Pill") is ineffective in relieving depression among patients with psychotic depression. Schatzberg, at one time, was the chief scientific officer of Corcept and was also the cofounder of the company. According to Corcept's website, he is still a scientific advisor. Despite the stuides of mifepristone showing negative results, the results were spun in a manner to make them sound as if they were positive (1, 2, 3, 4). In a press release, Schatzberg was quoted as saying that mifepristone "may be the equivalent of shock treatments in a pill." Right, with all of the negative studies, it's definitely shock treatment, meditation, and running a marathon all wrapped together in a capsule. Should he be paid "commensutate to the challenge" of trying to weave positive findings from negative results? I don't know what role, if any, he played in the misleading publications surrounding mifepristone. But in his role as chief of the scientific advisory board, I'd venture a guess that he had some involvement. But worry not, the negative results were not spun into positive findings for the sake of money, but for an altruistic love of patients with depression. I'm touched.

Schatzberg was also busted by yours truly putting his name on a duplicate publication that pimped Cymbalta, Lilly's antidepressant. The study presented data from the same set of patients who were involved in a previously published Cymbalta study. Scientific results are not meant to be published in nearly identical form in two different journals. But that didn't stop Schatzberg and his coauthors. If you've not read the lengthy post on this topic, please feel free to check it out in order to understand my cynicism regarding his recent speech.

Another quote from his talk:

We need to sit down with industry and come up with ways of interacting that are acceptable to both sides and fit with future guidelines. I have pledged to follow up on recent initiatives and work with Dr. Scully [APA's medical director] and our Board of Trustees to effect a new partnership—a partnership we can be proud of for what it contributes to the well-being of our patients and our profession.

I can only wonder what type of mutually agreeable interactions would meet Schatzberg's standards. Duplicate publication, serving as a scientific advisor for a company that writes scientifically dubious papers? And it appears that he's encouraging psychiatrists to be greedy -- take the money and don't feel bad about it. Taking industry money is perfectly acceptable in some instances, but it needs to be transparent, and there are plentiful examples of academics getting paid by industry and slanting science in a sponsor-friendly way.

And the clincher:

"The time has come," he said, "to be proud of what we do and to advocate for what we and our patients justly deserve."

Right, psychiatrists deserve to make as much money as possible bending science for corporate sponsors -- and they should be proud of it too. Am I being too cynical? Maybe. But when a guy with Schatzberg's record starts talking about psychiatrists needing to rake in more money from industry, it makes me think I'm living in Bizarro World. Get ready, APA memebers; it's going to be an interesting ride.

Corcept: Get Rich QUICK!

Corcept is getting attention again for its medication mifepristone (RU-486). According to one website (whose obnoxious font color and ''wise'' words I'll copy below)...

"In this case, you can buy a $10 drug development stock for under a buck, which makes a nice present for someone going to college or needing more money...

--SNIP--

Why all the interest in a stage three clinical trial drug development company that this summer reported a setback in trial outcomes?

Corcept is developing state of the art neuropsychiatric medications to treat Psychotic Major Depression, PMD, the number one psychiatric illness that paralyzes some 3 million people a year.

--SNIP--

In addition to PMD, Corcept is working with Eli Lilly and other partners to develop a patent portfolio of state of the art psychopharmaceuticals to treat Alzheimers, Catatonia, Cognitive impairment, Cocaine Addiction, Dementia, Delusion, Migraines, Postpartum depression, premature infants, stress, weight gain and a host of widespread concerns using the cortisol mechanism, with fewer side effects than previous medications.

The market for these medications is blockbuster size. CORT is remindful of some other drug companies owned like Alza, Smithkline and Syntex that hit home runs."

So what are you waiting for? Oh, you’re waiting for research that actually backs mifepristone's efficacy given its meager performance to date. Or maybe you’re waiting to see if anyone beside company employees and consultants (here and here) has anything nice to say about the drug. Well, it could be your loss! Personally, I’ll sit this one out.

Mifepristone (RU-486): Move The Goalposts Wider

Note: Some articles I mention below are without an abstract, so they received no link. The latest drama on mifepristone (RU-486, Corcept Therapeutics) continues to play out. DeBattista and Belanoff published a review (Trends in Endocrinology and Metabolism) discussing the great potential (in their eyes) for mifepristone in treating depression and possibly other conditions. Of course, let’s keep in mind that DeBattista owns shares in Corcept and is a consultant for them as well while Belanoff is the CEO of Corcept, so of course the review was park marketing, part science.

Robert Rubin and Bernard Carroll in a letter to the editor pointed out aptly that DeBattista and Belanoff’s review “makes exaggerated claims of efficacy.” They added that among the studies cited as proving evidence for mifepristone’s efficacy:
*One did not report a statistically significant benefit on any outcome measure
*Another “contained no statistical analyses of drug benefit whatsoever. The weak trend toward efficacy was created by alteration of the scoring method of a key rating scale (the Brief Psychiatric Rating Scale or BPRS). Had this scale been scored in accordance with its original psychometric validation, the results would have been even weaker than they were portrayed: only five, rather than 12, of 19 subjects who received high-dosage mifepristone would have shown a 50% reduction in the Positive Symptom Subscale (PSS) of the BPRS.
*The third study claimed a marginal benefit of mifepristone over placebo in producing a 50% reduction of scores on the PSS (p = 0.046). However, the statistical analysis failed to use Yates’ correction in computing the chi-square result. When the proper statistical test is used, or when the alternative Fisher exact test is used, then the result is clearly nonsignificant (p = 0.10). In addition, by analysis of variance the authors failed to find a significant main effect of mifepristone on any outcome measure of psychotic symptoms (with respect to the PSS) or general psychopathology (with respect to the BPRS) or depressive symptoms. The other two cited studies have appeared only in abstract form.

DeBattista and Belanoff, in their rather weak response, point out that one of the studies published only in abstract form is now in press and that it found significant results on the BPRS (as measured by a 30% reduction in scores) and several secondary measures. More on that study in a minute. They then point out that two small studies examining mifepristone which were criticized for failing to achieve statistically significant results by Carroll and Rubin yielded large effect sizes. I assume they mean pre-post effect sizes, meaning effect sizes that were not compared to placebo, as one of the studies did not use a placebo control. I’m not generally impressed when two small studies find large effects (not in comparison to a placebo) which do not carry over to larger studies. Note that DeBattista and Belanoff did not refute the points made about manipulating a rating scale to find a significant result or failing to use the proper correction for a statistical test, which also then pushed nonsignificant results to becoming significant. However, DeBattista and Belanoff make an excellent point when they state that “The first step with mifepristone is to demonstrate with greater confidence that the drug has a clinical effect.” Great point! That particular sentence sounds like a retreat from their earlier statements about mifepristone’s efficacy.

Now, as for that larger study on mifepristone for psychotic depression, which is now in press in Biological Psychiatry. DeBattista and Belanoff are the first two of eight total authors. The standard used to define response was a 30% reduction in BPRS scores. With a sample of 105 taking mifepristone and 116 taking placebo, the categorical analysis using Cochran-Mantel-Haenszel tests was barely significant (p = .041). Means and standard deviations were not reported for the BPRS, so who knows what happened in terms of effect size, but I’d bet it was not impressive. The results were more impressive for the Positive Symptom Subscale of the BPRS (p = .006), but it is again hard to calculate effect size without means and standard deviations.

The authors move on to reporting scores on a subgroup who had somewhat elevated Positive Symptom Scale Scores, and in this case means and SD’s are reported and it looks like about a .50 effect size favoring medication. How did this subgroup do on their overall BPRS score? Good question, because for this subgroup, only one measure (the aforementioned PSS) was reported. Apparently the patients with lower Positive Symptom Scores are not worthy of a subgroup analysis, likely because such an analysis would have shown unimpressive results.

The authors then move to another subgroup, 42 patients selected because they were “chronologically, the patients enrolled in the latter part of the study” and were being examined as part of an FDA analysis. This group showed the largest effects, according to my rudimentary analysis. It seems a little ridiculous to just report on the last 42 patients enrolled in the study. Why not report on the first 42? Oh, right, because when a group of 221 patients is enrolled, one draws a more valid conclusion from looking at the overall group rather than reporting on a random subset. Hello?? Maybe this is an attempt to send a message to the FDA – I’m not sure.

Now let’s move to the two biggest catches. One, there was no significant effect on depression (as measured by the Hamilton Depression Rating Scale). Let’s keep in mind that the patients had psychotic depression, which means treating the depressive symptoms might be nice.

The biggest catch was that everyone was allowed to take concomitant medication as their physician deemed appropriate. So the study really compared a mishmash of drugs plus mifepristone to a mishmash of drugs plus placebo. Not exactly the type of tightly controlled efficacy trial upon which one can make many conclusions. Especially considering that the authors reported little about which drugs were prescribed to which patients and how this may have influenced outcomes.

So, in the end, the study showed very little. More points to Rubin and Carroll. Methinks we need more people in psychiatry who are willing to throw the BS flag when they see products being overhyped.

I will say one good thing about the DeBattista et al study. The following quote was great: “The discovery of psychotropics to date has rested on serendipity and repetition of drugs with similar pharmacological profiles.” Unfortunately for them (as Corcept shareholders), the data do not support that their unique drug works any better than a me-too drug, and it is still unclear if mifepristone is much better than a sugar pill.

Link to an earlier post involving Carroll and Rubin here. Keep up the good work fellas.

Required Reading on Mifepristone (RU-486)

Health Care Renewal has a supremely excellent tale in the mifepristone saga that you simply must read.

Teaser...

..."Looking at the new report, one sees in the Acknowledgements that the first author was supported by Corcept. One also sees that a co-author, E. Ronald de Kloet, failed to disclose his relationship to the company: he is a member of Corcept’s scientific advisory board and, unless he has sold any, the owner of 60,000 shares of Corcept stock. One also sees that this basic science article is careful to follow the company’s marketing message and branding language on the putative efficacy of mifepristone for PMD. For instance, it states, “The glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression.” These basic scientists also stated, “recent clinical studies have shown that the glucocorticoid-receptor (GR) antagonist mifepristone relieves symptoms of psychotic depression after a remarkably brief treatment period of 4 or 8 days.” None of the cited studies shows anything of the sort. We then read, “… similarly to its clinical efficacy, mifepristone’s effects on adult neurogenesis are rapid and positive, and may therefore be important for its mechanism of action.”

What is the deal with "similarly to its clinical efficacy" -- there is no proven clinical efficacy. The post goes on to discuss how the article makes for great marketing copy (which was likely its intent all along). A basic scientist can play marketing waterboy as well as the clinical trials folks!

Link to the excellent HC Renewal post here. More on mifepristone here and here.

Corcept: What Did I Tell You?

Don't let it be said that I didn't warn you. Finding a positive result for Corlux (mifepristone) without having to bend reality too greatly would probably help the company. If two trials failed, though, why would the current trial succeed?

SEC Filing Below...

Item 3.01 Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing.

Nasdaq has notified Corcept Therapeutics Incorporated that the Company is not in compliance with continuous listing standards for inclusion on the Nasdaq Global Market because (i) pursuant to Nasdaq Marketplace Rule 4450(a)(5), the Company’s price per share for its Common Stock had closed below the minimum $1.00 per share requirement for 30 consecutive business days, and (ii) pursuant to Marketplace Rule 4450(a)(3), the Company’s stockholders’ equity reported on its Form 10-Q for the period ending September 30, 2006 did not comply with the minimum $10 million requirement.

The Nasdaq notifications were provided in two letters dated November 10, 2006. On November 16, 2006 the Nasdaq staff determined pursuant to Marketplace Rule 4814(b) to adjust the period of time required for Corcept to disclose the receipt of the two letters to no later than the close of business on November 22, 2006.

Pursuant to Marketplace Rule 4450(e)(2), the company has a 180 day grace period to regain compliance with Nasdaq’s minimum bid price requirement. In order to regain compliance, the bid price of the Company’s common stock must close at $1.00 or more per share for a minimum of 10 consecutive business days anytime before May 9, 2007.

Nasdaq has advised the Company that under Marketplace Rule 4803, the Company has until December 4, 2006 to provide Nasdaq a specific plan to achieve and sustain compliance with the minimum stockholders’ equity standard.

Someone's Betting on Corcept

I just saw a brief headline that...

"Corcept Therapeutics announces $3 mln private equity financing Co announces that it has entered into a definitive agreement with certain accredited investors for the private placement of 3 mln shares of its common stock at a price of $1.00 per share. Pursuant to the agreement, the investors, who are led by Paperboy Ventures, have irrevocably committed to purchase the shares."

There are only three logical explanations:
1) These people are looking for a tax write-off when Corcept collapses due to the poor performance of its Corlux (mifepristone/RU-486) product in treating psychotic depression. When the FDA determined the drug is not approvable, they’ll drop a tax bracket or two.
2) These investors have been snowed by someone; they don't know what they're doing. They haven't read posts such as this, this, and this. They don't know that the efficacy of Corlux is nothing to write home about, as it appears to help little with depression and not particularly greatly with psychotic symptoms either.
3) They know something that I don't. Maybe the FDA, circa vagus nerve stimulation, is going to approve Corlux regardless of its actual efficacy.

Yo Chuck, We Got Some Nonbelievers Out There (Corcept Plunges)

Remember Corecpt Therapeutics? They were testing mifepristone (aka RU-486 or Corlux) for psychotic depression. Well, again, things did not go exactly as planned. As indicated earlier, they found that the medication was no more efficacious than a placebo for depression in one trial, a result that was replicated by a second failed trial. One has to admire their ability to make excuses, as their press release states “As was the case in study 07 [the prior failed trial], there was an unusually high placebo response rate in Study 09.” When all else fails, blame the placebo! Two failed trials or not, Corcept marches on: They are enrolling patients in a third trial and plan to announce results in early 2007. Here at the CPP Blog, I will be watching anxiously. If they get one out of three, will the FDA give it a stamp of approval?

Of course, one can only guess how Dr. Charles Nemeroff felt about this latest turn of events. After all, he is on the scientific advisory board for Corcept and their stock really took a beating (down 34% in one day) upon release of the second negative trial. You may remember Chuck as the researcher who published positive comments in a review article regarding mifepristone based on a study containing a whopping sample of five patients. The article contained no disclosure of any conflicts of interests, such as the fact that he was on the advisory board for the company whose drug he was pimping based on very skimpy data. You can refresh your memory about the story here. Let’s hope, for his sake, he was able to move his shares before the latest press release was issued!

A Month in The Life of Chuck "High Life" Nemeroff

The psychiatry world is belatedly exhibiting outrage toward a man whose ability to lure pharma cash seems to know no bounds. He may be the textbook case of a key opinion leader. Of course, I speak of Charles "Bling Bling" Nemeroff. Rather than list the many questionable at best behaviors he has exhibited, each of which has called into question his standing as a scientist as opposed to a blatant drug marketer, I just want to a) direct everyone to a detailed list of his speaking engagements from GlaxoSmithKline and b) discuss a month of living the High Life, Nemeroff Style.

As is well known by now (1, 2), Nemeroff appears to have not been particularly forthcoming about the huge amounts he was making while moonlighting for every drug company on the planet (see below) despite requirements that he do so. According to psychiatrist Danny Carlat:

From 2000 to 2006, GSK paid Nemeroff a total of $960,488. Note that this was not research grant money, or money for Emory's psychiatry department. These were fees that went into his personal bank account, which he earned by either sitting on GSK's Advisory Board, or speaking to doctors about GSK products. His typical fee for a talk was $3500 plus expenses, but sometimes he made more.

Of this $960,488, the total amount he disclosed to Emory [his employer, to whom he was required to report such income] was $34,998.

According to a GSK document hosted by Senator Charles Grassley, Nemeroff took in over $20 grand in one month from speaking engagements for GSK. Not bad work if you can get it, eh? And this month doesn't seem unusual for Nemeroff. These are only his speeches for GSK -- he also gave speeches for several other companies. The document goes on and on -- 39 pages of paid speech listings, nearly all of them featuring Nemeroff. I just picked 03-30-00 to 04-30-00 because they were on the first pages of the document, which covers expenses from 2000 to 2008 for Dr. Bling Bling.

Nemeroff GSK Honoraria from March 30, 2000 to April 30, 2000

Date	Speaking Fee
03/30/2000	$4000
04/12/2000	$2500
04/19/2000	$4000
04/20/2000	$4175 (includes some 'expenses'; I suspect $4000 was the speaking fee)
04/27/2000	$4000
04/30/2000	$2500
TOTAL	$21, 175 (probably $21,000 excluding travel expenses)

Imagine making $20k in a month for basically reading slides a few times that were quite possibly entirely written by a drug company. And many of these talks were accompanied by posh meals, the kind that myself and most of my readers might eat once or twice a year.

Here's a Nemeroff disclosure from a recent journal article:

Dr Nemeroff has received grants from or performed research for the American Foundation for Suicide Prevention, AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, Inc, Janssen Pharmaceutica, NARSAD: TheMental Health Research Association, the National Institute of Mental Health, Pfizer Pharmaceuticals, and Wyeth-Ayerst Laboratories; has been a consultant to Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb, Corcept Therapeutics, Cypress Bioscience, Cyberonics, Eli Lilly and Co, Entrepreneur’s Fund, Forest Laboratories, Inc, GlaxoSmithKline, i3 DLN, Janssen Pharmaceutica, Lundbeck, Otsuka America Pharmaceutical, Inc, Pfizer Pharmaceuticals, Quintiles Transnational, UCB Pharma, and Wyeth-Ayerst Laboratories; has been on the speakers bureau for Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Pharmaceuticals; is a stockholder in Acadia Pharmaceuticals, Corcept Therapeutics, Cypress Bioscience, and NovaDel Pharma Inc; is on the board of directors of the American Foundation for Suicide Prevention, the American Psychiatric Institute for Research and Education, the George West Mental Health Foundation, NovaDel Pharma Inc, and the National Foundation for Mental Health; holds patents on a method and devices for transdermal delivery of lithium (US 6,375,990 B1) and on a method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (provisional filing April 2001); and holds equity in Reevax, BMC-JR LLC, and CeNeRx.

No, I didn't make that up. As Ed Silverman wrote at Pharmalot, "It also raises a question - when he did find time to do anything else?"

What's Next for Schatzberg?

An advertisement in the Psychiatric Times (page 34 of .pdf) calls for applicants for the Chair of the Department of Psychiatry and Behavioral Sciences at Stanford University, a position now filled by Dr. Alan Schatzberg. The Stanford Psychiatry Department webpage currently states, in part:

Under the direction of the Chairman and Chief Alan F. Schatzberg, M.D., the Stanford University Department of Psychiatry and Behavioral Sciences, a center for the advancement of psychiatric practice, research and education, has three goals:

• To advance the understanding of the etiologies of psychiatric or sleep disorders and to lay the foundation for new treatment development.
• To develop innovative treatments and to deliver comprehensive services on a continuum of care to patients in a high quality efficient and compassionate manner.
• To train medical students, residents and clinical and research fellows in the science and practice of psychiatry and sleep medicine.

Looks like Schatz is out. I have noted previously that Schatzberg was deeply involved with a duplicate publication that pimped Cymbalta. Schatzberg's close involvement with Corcept, maker of mifepristone (Corlux), has also raised eyebrows. Mifepristone has been an utter failure in clinical trials, but the manufacturer has attempted to spin the data in ways that should be obvious to anyone with a smidgen of critical thinking skills. Charles Grassley has hit Schatzberg as part of the investigation into the tangled web of conflicted interests involving psychiatrists and drugmakers. There is also some evidence that Schatz was involved in the launch of Zyprexa for bipolar disorder.

Schatz is apparently out as department chair. I wonder who will take his place...

Thanks to an alert reader for the tip.

When to Say Sorry?

In a recent post, Daniel Carlat apologized to Charles Nemeroff for nicknaming him "Bling Bling" in a prior post. So what? Who cares? Well, I think we need to take a look at what behavior requires an apology and what does not. I'm not saying I have the answers, but I think the issue is quite important.

Let's look at some documented issues regarding Nemeroff:

ARISE-RD 1: Nemeroff was an author on a study (called ARISE-RD) examining the use of risperidone as an antidepressant. The study results did not demonstrate that the drug worked, especially after the authors issued a correction indicating that one of the findings in the published version of the study was incorrect (oops -- sorry that we mentioned that the drug worked; we screwed up -- it really did not work).

ARISE-RD 2: The study results were clearly not reported in full, leaving open the possibility that unfavorable data for risperidone was simply swept under the rug.

ARISE-RD 3: The study was published in a journal of which Nemeroff was the editor. Strangely, he did not report that he had a financial conflict of interest in the study, though the journal requires such relationships to be disclosed.

ARISE-RD 4: Authorship was switched around, leading one to wonder if the authorship line was an accurate reflection of who contributed significantly to the study or if it included an effort to stamp on the names of several "key opinion leaders" in order to improve the study's marketing value (1, 2 ).

I strongly encourage readers to read the linked posts above in order to plumb the depths to which this study appeared to be flawed. But there's more...

VNS: In his role of journal editor, Nemeroff again failed to disclose relevant conflicts of interest regarding a study that appeared in his journal and upon which he was an author. Read more on that tale here and here.

Mifepristone/RU-486: Nemeroff wrote an article reviewing various treatments. One treatment he mentioned was mifepristone (Corlux/RU-486). Nemeroff serves in a paid advisory role to Corcept, maker of the drug. He concluded, based upon incredibly weak evidence, in the review, that mifepristone was "very effective" in treating psychotic depression.

Lithium patch: In the same review article as mentioned above, Nemeroff mentioned that the lithium patch improved tolerability and compliance. So the patch made patients stick with treatment better and lowered the side effect burden. Oh, and Nemeroff did not cite a single source to back up these claims. Um, the entire point of a review article is to make claims and back them with sources. Nemeroff holds the patent for the lithium patch, by the way.

David Healy: According to some sources (not entirely confirmed, though I believe it), Nemeroff was part of the effort to get David Healy ousted from his position at the Univeristy of Toronto. It's a long story, worth reading about here and here. As readers of my site know, I have cited Healy's work here many times due to his close knowledge of data regarding psychiatric medications (particularly SSRI's) -- he's a good scientist with, in my mind, a very strong conscience. If Nemeroff was involved in getting Healy's position rescinded, then I say shame on him.

CME and Dr. Nemeroff: Dr. Nemeroff, like many key opinion leaders, is willing to set his name on journal supplement papers which are then used for continuing medical education. Daniel Carlat has a great post about a recent CME activity, upon which Nemeroff was an author, that seemed to magically transform unfounded ideas into "science" by just adding a sprinkling of money from the sponsor, Bristol Myers Squibb. Kinda made me think of a Chia Pet for some reason. Suh-Suh-Suh-Science! to the tune of Chuh-Chuh-Chuh-Chia!

So looking at the above list of items involving Nemeroff, I ask readers: Is it okay to nickname someone "Bling Bling" or to nominate someone for a Golden Goblet award? Please chime in with a comment to let me know. Is it acceptable sarcasm or is it character assassination, or something else?

The Point: I'm not in favor of name calling, nor am I in favor of being a jerk. But where does one draw the line? Where is the line drawn between acceptable reporting on controversial and important issues and being a bully? Over at the Drug Wonks blog, there are several posts that take aim at Steve Nissen and others, often using a nastier tone than nicknaming people "Bling Bling." Plenty of mudslinging occurs in blogs and in the "old media" -- watch most of the talking heads on so-called cable "news" networks and see what I mean. How often, and to what degree, is someone allowed to use sarcasm before it becomes rude and bullying? Part of writing is entertaining one's audience, and let's face it -- sarcasm can be very entertaining. How is a blogger to be entertaining, stick to the facts, and bring important information to readers without crossing the line into being offensive? I don't know. Perhaps you do -- again, leave a comment and see if you can shed light on this issue.

Iloperidone: Vanda Shareholder Train Wreck

Many months back, when shares of Vanda Pharmaceuticals were going for 29 bucks, I warned y'all: Their main product, iloperidone, showed all the signs of being a dud. It has been in the clinical trials stage of development for about a decade and it had yet to receive FDA approval. Um, if a drug was of significant benefit, do you really think it would have been in late-stage development for 10 years? In December 2006, I wrote:

As for iloperidone, one article forecasted that it would hit the market in 2001! Further digging indicated that Titan, which holds the license for iloperidone (to some extent, anyway), was in a spot of trouble for allegedly hiding the drug’s side effect profile. In 1997, according to a report filed with the SEC, “the Company does not have the funds necessary to complete the clinical development of Iloperidone and is currently pursuing several financing alternatives including corporate partnering arrangements and off balance sheet financing to complete development of Iloperidone.” I assume this is where Vanda got involved. I could find not a single published trial of ilopderidone in either PubMed or Clinicaltrials.gov. If anybody can direct me to clinical trials data for this product, I’d love to see it! So this drug has been in the clinical trials phase of development for nearly a decade, and there is no published data to show its efficacy. I’m not impressed.

My personal opinion is that you are better off burning your money than investing in Vanda after the huge jump earlier this week.

Now, according to Reuters, Vanda received a not approvable letter from the FDA "over concerns of efficacy" regarding iloperidone in the treatment of schizophrenia. Ouch. This after the drug was ludicrously named "Fiapta," then "Fanapta." Hello?? Vanda shares can now be had at about a dollar per share -- down about 95% from when I initially warned everyone to steer clear of the company's stock.

There is always a chance that the FDA has a change of heart; it's possibly even worth buying at this point, as even obvious dogs have their day on the market occasionally, such as Corcept Therapeutics. I have no faith that any of Vanda's products are worth anything clinically, but I think they might be able to BS enough analysts and investors to help drive up the price up a few bucks per share. Note that this is not official investment advice.

Charles Nemeroff, Consultant Extraordinaire

The key opinion leader of key opinion leaders. Or Boss of Bosses, if you prefer. In any case, take a peek at the following from Charles Nemeroff's page on the University of Miami's website. Seems like something must have happened in 2006 to slow down Chuck's momentum...

What? This is old news? Yeah, I know. But I just hadn't written much about our friends in the world of drug sales/"academics" lately, so I just had to do this.

Pharmaceutical and Clinical Research Company Scientific Advisory Boards

Abbott Laboratories
- Consultant, Abbott Laboratories, Diagnostics Division, 1986-1992.
- Research and Education Advisory Board for Psychiatry
- Member, 1990 - 2006
- Executive Board, 1991 - 1993, 2003 - 2006
-Antidepressant Advisory Board, 1991 - 1992

ACADIA Pharmaceuticals Clinical Advisory Board
- Member, 2000 - 2006.

AstraZeneca Pharmaceuticals
- Psychiatry Advisory Board, 1997 - 2001.
- Chairman, 1999 - 2002.
- Neuroscience Scientific Advisory Board, 1999 - present.

Bristol-Myers-Squibb
- Antipsychotic Advisory Board, 2003 - 2006.
- Antidepressant Advisory Board, 2003 - 2006.
- EMSAM Advisory Board - Chairman, 2005-2006.

Cephalon Pharmaceuticals
- Scientific Advisory Board, 2002

Comprehensive Neuroscience, Inc.
- Scientific Advisory Board, 1999 - 2004.

Corcept
- Scientific Advisory Board, 2001 - 2006

Cyberonics
- Scientific Advisory Board, 2002 - 2006.
- Chair, Mechanism of Action Board, 2003 - 2006.

Cypress Biosciences, Inc.
- Board of Directors, 2001 - 2004
- Consultant, 2004 - 2006

Eli Lilly and Company
- Psychiatry Advisory Board, 1990 - 2000.
- Bipolar Advisory Board, 1998 - 1999.
- Consultant, 2002 - 2003.
- Global Neuroscience Advisory Board, 2005 - 2006.

Forest Laboratories
- Citalopram Clinical Advisory Board, 1997 - 2002.
- Psychiatry Scientific Advisory Board, Chairman, 1999 – 2008.

GlaxoSmithKline Advisory Board of Psychiatrists
- Chairman, 1991 - 2004.

Janssen Pharmaceuticals
- Mood Disorders Advisory Board, Member and Chairman, 1998 - 2004.
- Topiramate Advisory Board, Member and Chairman, 1999 - 2001.
- Antipsychotic Advisory Board, Member, 1999 - present.

Johnson & Johnson Scientific Advisory Board, 2007- present.

Lundbeck
- Consultant, 2006

Merck Sharp & Dohme Research Laboratories
- Consultant, Neuroscience Research Center, 1994.
- Mood Disorders Advisory Board, 1999 - 2003.

Merck-MedCo Mental Health Advisory Board
- Member, 1996 – 1998

Mt. Cook Pharma
- Board of Directors, 2007 - Present

Neurocrine Biosciences
- Scientific Advisory Board, 1994 - 2004.

Neuronetics
- Scientific Advisory Board, 2006

Novadel Pharma
- Board of Directors, 2003 - present
- Chair, Scientific Advisory Committee
- Member, Compensation Committee
- Member, Nominating Committee

Novartis Pharmaceutical Company
- Bipolar Advisory Board Chairman, 2001 - 2003.
- Pediatric Bipolar Advisory Board, 2002 - 2003.
- Antidepressant Advisory Board, 2006.

Organon Pharmaceuticals Psychiatry Advisory Board
- Member, 1997 - 2004.

Otsuka Psychiatry Advisory Board
- Chairman, 2003 - 2006.

PharmaNeuroboost
- Scientific Advisory Board, 2006 – present.

Pfizer Pharmaceuticals
- Clinical Neuroscience Advisory Board, 2004 - 2006.
- Chair, Antipsychotic Advisory Board, 2004 - 2006.

Quintiles Scientific Advisory Board, 2004 - present

Revaax
- Stockholder

Roche Laboratories, a Division of Hoffman-LaRoche, Inc.
- Mania Advisory Board, 1993.
- Pharmocogenomics Advisory Board, 2006

Sanofi/Synthelabo
- Psychiatry Advisory Board, 2002 - 2005.

SciRex
- Scientific Advisory Board, 1999 - 2003.

Solvay Pharmaceuticals Psychiatry Advisory Board
- Member, 1991 - 1999.
- Chairman, 1991 - 1999.
- Antipsychotic Advisory Board, 2005 - 2006.

Somerset Pharmaceuticals Psychiatry Advisory Board
- Chair, 2000 - 2004.

Vela Pharmaceuticals
- Scientific Advisory Board, 2001 - 2002.

Wyeth-Ayerst Psychiatric Advisory Board
- Chairman and Member, 1995 - 2002.

Uh-Oh Chuck, What About the Disclosure? OR Go Team MAOI!

Introduction: As longtime readers can surmise from the headline, this post is about Dr. Charles Nemeroff. And the Dalai Lama. Let's start from the beginning. Nemeroff was featured in a CME activity on Medscape. To view it, you'll need to complete a free registration at Medscape. For those new to the wonderful world of CME, note that while CME stands for continuing medical education, it is more accurate to refer to it as commercial medical education -- it's paid advertising, dare I say cheerleading. It is rather disheartening that physicians who wish to keep their licenses must sit through a bunch of advertisements as opposed to less biased, more educational forms of training. For more on CME in general, read my earlier posts here and here, or check out Daniel Carlat's excellent work (1, 2, 3, 4, 5 ).

The Present Story: Nemeroff, in the aforementioned CME activity, discusses the transdermal patch for selegiline, a monoamine oxidase inhibitor (MAOI) and how it may serve as a good treatment option for people with depression. Here are a couple of quotes from Nemeroff:

The limited use of oral monoamine oxidase inhibitors (MAOIs) over the past decade or so has been driven largely by physicians' concerns that they might potentiate hypertensive reactions when they interact with tyramine in foods. A new transdermal system is currently available that enables the MAOI to avoid first-pass metabolism by bypassing the gut, thereby reducing the chance of hypertensive reactions caused by tyramine.

The Pande study, which I believe was done when Pande was at Lilly, compared 20 patients with atypical depression treated with fluoxetine and 20 treated with the nonselective irreversible MAOI, phenelzine. Efficacy was about equal. Certainly other data and my own experience would suggest that MAOIs are superior to SSRIs and TCAs [for atypical depression].

A case that is treated successfully (of course) with transdermal selegiline is discussed during the activity in some depth. All's well that ends well. Clearly, the CME activity backs the use of transdermal selegiline. While it discusses some of the risks associated with MAOI treatment, the program states that the transdermal system avoids many of these issues.

Chuck's Conflicts: Nemeroff lists the following disclosures in the CME activity:

Reunette W. Harris Professor and Chairman, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

Disclosure: Grants: AstraZeneca Pharmaceuticals, LP, Bristol-Myers Squibb Company, Forest Laboratories, Janssen Pharmaceutica, National Institute for Mental Health, Pfizer Inc, Wyeth-Ayerst Laboratories, Consultant: Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb Company, Concept Pharmaceuticals, Ltd, Cypress Bioscience, Inc, Cyberonics, Inc, Eli Lilly and Company, Entrepreneur Fund Inc, Forest Laboratories, GlaxoSmithKline, H. Lundbeck A/S, Ingenix i3 DLN, Janssen Pharmaceutica, Otsuka America Pharmaceutical, Inc, Pfizer Inc, Quintiles Transnational Corporation, UCB Pharma, Wyeth-Ayerst Laboratories; Speaker: Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc.; Stockholder—Acadia Pharmaceuticals; Corcept Therapeutics, Inc; Cypress Biosciences; NovaDel Pharma Inc.; Board of Directors: American Psychiatric Institute for Research and Education, NovaDel Pharma Inc, National Foundation for Mental Health

As you can gather, Nemeroff is a busy guy! According to the above, he is a consultant for 18 drug companies and a speaker for four companies. The plot is about to thicken (or, perhaps, sicken) notably...

The Missing Disclosure: Remember how the above CME was all about pushing a newer, safer MAOI drug for depression? Well, it just so happens that Nemeroff is the co-chair of the Scientific Advisory Board for CeNeRx, a company that is developing a (you guessed it) newer, safer MAOI drug for depression! Note that Nemeroff did not mention his position with CeNeRx in his disclosure for the Medscape CME activity. Here's what the CEO of CeNeRx had to say about the MAOI they are testing:

In contrast to other MAO inhibitors, our third generation RIMA series is designed to bind selectively and reversibly, with the goal of significantly reducing the cardiovascular risks and other side effects typically associated with the MAOI class. These safety results, along with the high plasma levels and favorable pharmacokinetics demonstrated in the study, support advancing Tyrima into a multiple dose safety study in late spring.

Note the similarity to what was being said about the MAOI patch in the Medscape CME. Let me put this plainly: Nemeroff stumps for an MAOI in a CME activity, yet does not disclose that he is being paid by a company which also manufactures an MAOI. Can you say "hiding a blatant conflict of interest?"

The Dalai Lama: Nemeroff is appearing with His Holiness the Dalai Lama for a presentation on depression at Emory University. Thankfully, Nemeroff is not scheduled to speak about MAOI's. He is actually scheduled to speak about the relationship between early life experience and depression, about which the research is quite interesting and important. However, given the history of Nemeroff's scientifically questionable behavior (read a summary here, which has links to more detailed stories), it strikes me as strange that he'll be presenting alongside the Dalai Lama.

Golden Goblet: Does this earn Nemeroff a nomination for a Golden Goblet ? I believe so.

Taking a Break

I have several other pressing matters to which I must attend for the next little while. I will likely not be posting until the end of December or perhaps early January. However, I will likely be doing some writing on at least some of the following topics in the interim so that I am ready to hit the ground running upon my return.

• Texas Medication Algorithm Project
• SSRIs and Suicide
• Troubles associated with having children when older
• Reply to Herb on VNS
• Corcept and mifepristone