New Year, New Look

I've decided to change the look of the site. If you feel strongly one way or the other, let me know.

Changes?

Alex Chernavsky has written many thoughtful comments on this blog, which I greatly appreciate. His latest comment is about the potential Zetia coverup, but it could have been written in response to many other topics and been just as apropos. I wish I could disagree with him, but I think he has a point...

What strikes me in these cases is just how little progress we are making. I've been following this stuff for the last 12 years or so, and I see a lot of exposés -- but not a lot of substantial changes that result from those exposés.

For example, if you look back to 2000-2001, you'll see that David Willman -- a reporter for the Los Angeles Times -- won the Pulitzer prize for a series of articles about corruption in the pharmaceutical industry. His articles are first-rate and are still worth reading today:

http://www.pulitzer.org/year/2001/investigative-reporting/works/

But that was seven years ago. Are we in a better position today? Maybe I'm being overly harsh, but I just don't see a lot of progress made. Big Pharma has corrupted medicine -- and especially psychiatry -- and now has its sights set on psychologists.

Zetia: But Why Would We Show You the Scary Data?

Alex Berenson has potentially unearthed another December Surprise for a major drug company. You may recall that last December, Berenson started writing on the Zyprexa mess (1, 2), which everyone can now read about through accessing the now-infamous Zyprexa documents over at Furious Seasons.

It now appears that there have been at least three unpublished studies regarding the health effects of Merck/Schering Plough's anticholesterol drug Zetia that point to the drug causing liver problems. Read the full article at the New York Times. Only time and a little sunshine on these studies will reveal whether this is a big story, but it is important to note that this is not particularly surprising -- on this modest blog, I have documented several incidents of data pointing to poor efficacy and/or drug risks being buried (1, 2, 3, 4, 5, 6 are just a few examples). Many other blogs, newspapers, and other sources have also documented such problems. Hiding data is an everyday occurrence. For whatever new medication is approved, the public dissemination of risks and benefits are managed by the sponsoring company and what would be the company's motivation to provide data that paint a scary picture of their new drug?

Social Phobia: How Common?

So how common is social phobia? Some varying answers:

1. Is it 7% at any one point in time and 12% over a person’s lifetime?
2. Is it 2% at any one point in time and 6.65% over a person’s lifetime?
3. Is it 1% at any one point in time and 2% over a person’s lifetime?

These estimates are all derived from peer-reviewed epidemiological studies on the topic and it is clear that they vary greatly. Let’s think about social anxiety for a moment…

Social phobia/social anxiety disorder appeared on the mental health scene with a vengeance about a decade ago thanks in large part to a wonderful “educational” campaign by Cohn & Wolfe, a PR firm hired by SmithKlineBeecham to spread the word about this allegedly underrecognized and undertreated condition that was devastating the lives of untold tens of millions across the globe (1, 2, 3).

The 12% lifetime prevalence figure is oft-cited, but it is important to consider that credible evidence has also placed the figure as low as about 2%. Yes, I am aware that the 12% figure is from the U.S. and the 2% figure is from Italy – but does anyone want to argue that Italian and American cultures are so different that social anxiety in these cultures would really differ by a factor of six?

Perhaps someone with more energy can look through these papers (as well as the many other similar epidemiological studies that have been conducted) and take a stab at why the estimates vary so greatly. Might it have something to do with where we set the cutoff? Might it be that the more we label mere shyness as pathology, the higher our rates of social anxiety disorder? Seems that we might want to consider whether a disorder actually causes significant impairment before we call it a disorder, eh?

Social phobia is often listed as the third most common mental disorder (4, 5), but it seems we had better start asking more questions and show more skepticism before blindly accepting that this condition is running rampant.

Bipolar Explosion, Spot-On Parody, and Other Highlights

A number of great posts have emerged across the wonderful world of health blogs as of late.

In particular, check out the following on bipolar disorder, which must be spreading like wildfire these days:

• David Healy and Joanna LeNoury have a new paper on the influx of bipolar disorder cases. Consider it required reading. Key opinion leaders, Big Pharma, astroturf patient support groups, Brandon and the Bipolar Bear, and more. Read it now. Furious Seasons has some choice excerpts
  
• Furious Seasons has a whale of a post on living with "bipolar disorder." As a very bright and thoughtful man who has been diagnosed with bipolar for decades, and has lived through many an interesting experience, his discussion of bipolar is quite timely and fits nicely into the present mania of diagnosing bipolar every time somebody does not respond well to antidepressants.
• The name of the post says it all: Is early-onset bipolar disorder simply normal childhood? Read it at Psych Central. I can't resist taking one choice quote from the post (quote from psychologist John Rosemond):
  
• In their book and in the May 2007 issue of their newsletter, available through their website, the Papoloses recommend against using the word “no” with a bipolar child “because it will trigger a meltdown.” When they were toddlers, my children often suffered wild seizures at the sound of “no.”

On the topic of disease mongering, the best parody I've yet seen may have just been penned by the incredible Pharma Giles. The Pharma Giles take on the Montel Williams fiasco is also a great laugh.

The Scientific Misconduct blog has a post on the conflict between integrity and money, which somehow just keeps rearing its head on this site and others.

Mind Hacks notes an example of poor journalism regarding an alleged cure for Alzheimer's.

Peter Rost, ever the excellent self-promoter (meant as a compliment), has a website promoting his expertise as a pharmaceutical marketing consultant and expert witness. After tracking his work for a while, I am convinced -- I'd certainly hire him.

The Carlat Psychiatry Blog is just on-fire all around. No need to single out a particular post.

Pharmalot points out that Wyeth just got slapped by the FDA for a highly misleading ad about Effexor. Read the FDA letter -- this ad is well beyond a little bit misleading.

Key Opinion Leader Provides False Information in Psychiatry CME

Just when I thought it was safe to stop writing about the ARISE-RD study, which was an attempt to demonstrate the efficacy of risperidone (Risperdal) for depression, even more evidence of misleading salesmanship regarding the study surfaces. Feel free to read six prior posts regarding the study, described in a bit more detail here.

Here's the rub. Dr. Charles Nemeroff is the presenter for this continuing medical education activity entitled Add On Atypical Antipsychotics Efficacious in Short Term for Unipolar Depression. This post concerns slides 5, 6, and 9, which reference the aforementioned ARISE-RD study, which examined the use of risperidone as an add-on to citalopram (Celexa) in treating depression. The full presentation is available for your examination.

Slide 6 reads in part:

• Global Impressions of Sexual Functioning scores improved significantly in men and women (p < .02) with RIS augmentation.
• RIS may ameliorate sexual dysfunction associated with SSRIs.

There is a reference to a published study in Neuropsychopharmacology at the bottom of the slide. The kicker: The published study contains no mention of improved sexual functioning on risperidone. This is called lying. Remember, Nemeroff was an author on the study published in Neuropsychopharmacology; he'd know if sexual functioning was referenced in his article, so there is no pleading ignorance on his part.

Slide 9 reads in part:

• Augmentation options for treatment-refractory depression include adjunctive atypical antipsychotics.
  -Controlled studies: short term efficacy with OLZ, ARI, RIS [risperidone]

This is a baldfaced falsehood. The study took people who had not responded to citalopram treatment, then added risperidone to the mix. There was no placebo control during this phase. So it was not a controlled study and should not be referred to as a controlled study in Nemeroff's presentation.

In fact, here is what the lead author (Mark Rapaport) of the ARISE-RD study had to say about its results in a letter to the editor (currently in press):

The paper repeatedly states in Abstract, Methods and in Discussion that continuation of risperidone augmentation therapy was not more beneficial than placebo, and hence the working hypothesis was disproven...

I would like to thank the reviewers and the editors of Neuropsychopharmacology for having the courage to allow us to publish this negative finding.

Compare and contrast: Nemeroff's presentation indicates that the study was a controlled trial showing that risperidone was more effective than placebo. The lead author admits that the study was a "negative finding" and that risperidone was "not more beneficial than placebo."

To summarize, Nemeroff did the following:

• Claimed that a peer-reviewed study showed risperidone improved sexual functioning, when the effects of treatment on sexual functioning were not even mentioned in the paper.
• Claimed that the study showed risperidone to demonstrate efficacy over placebo, which it in fact did not.
  

This is what passes for education for physicians. Being lied to about study results is how physicians receive continuing medical education to keep them abreast of the latest research findings so that they can better serve their patients. If you are not disgusted, you are not paying attention. It is far from reassuring that this incident involves one of the biggest names in academic psychiatry.

American Psychological Association Awakens From Slumber, But For How Long?

As reported on a pair of my favorite blogs (Pharmalot and the Pharma Marketing Blog ), the American Psychological Association Task Force on External Funding has issued a wake-up call to psychologists. To briefly summarize, when legendary psychologist Philip Zimbardo was APA president in 2002, he was taken aback by the corporate-sponsored largesse at the American Psychiatric Association convention. Being a forward-looking fellow, Zimbardo saw the writing on the wall: As psychologists move toward attaining prescription privileges, drug companies would descend on the profession like vultures.

Read the article based on the committee's findings here. It's very good reading. They make a long list of recommendations, 24 to be exact, including highlights such as...

• External funds (i.e., drug money) should not be a part of APA's core budget
• Exhibitors at APA conventions should not pimp their wares in bizarre manners (see the American Psychiatric Association convention for examples of marketing gone awry)
• APA should consider not allowing continuing education credits for industry-sponsored courses
• No drug pens or other branded material on display where psychologists work
• Psychologists should not accept gifts from corporations (including meals)

Here's the deal. APA has been pushing hard for psychologists to obtain prescription privileges for several years. At this point, they can point to modest success at best, as psychologists in New Mexico and Louisiana can prescribe psychiatric meds after some additional training and experiences. There has been a lot of debate about whether psychologists should be allowed to prescribe or not, but that is not the point of this post. The point is to make predictions. Here comes the future.

APA will not heed the recommendations of their task force, at least not many of the important ones. Should psychologists attain prescription privileges in more states over the next 10 or 2o years, drug companies will throw their money at psychologists in the following ways (and then some)...

• Gifts, small and large
• Sponsoring continuing marketing, er, education
• Funding APA directly
• "Unrestricted" research grants
• Psychologist-to-psychologist marketing. Paying psychologists to "educate" other psychologists about medication.
• Having psychologists rubber stamp their name on ghostwritten, pro-industry "research" pieces

Prediction 1. APA won't turn down money from drug companies. They may try to do so for a few years, but eventually they will not be able to resist the lure of cash. Of course, they will insist, as does the American Psychiatric Association, that accepting money from corporate sponsors will not impact the mission of the organization.

Prediction 2. APA and the various state psychological associations will not restrict CE credits based on who funds them. There is already grumbling about a lot of what passes for continuing education of psychologists being nothing more than fluff, puffery, or a feel-good session. That being the case, there will be many who will be drawn to the allure (however fake it may be) of science surrounding drug company-sponsored continuing education. Of course, some psychologists already receive pharma-funded continuing ed, but there is much room for drug companies to move into "educating" psychologists about their products.

Prediction 3. Psychologists will become more involved in drug research. Some people have stated, I believe quite naively, that if psychologists become more involved in drug research, they will clean it up. Um, what makes psychologists more capable of cleaning up the dirty research system (1, 2) than the current body of medical researchers. Seems like a rather arrogant belief to think that psychologists will clean up a system of biased clinical research just because they are psychologists. Psychologists will also be involved in signing their names onto puff pro-drug pieces.

I could be wrong. APA could take a stand. But APA has dedicated many resources to getting psychologists on-board as prescribers. Just read through APA press releases and see their enthusiasm (1, 2). So don't make a bet on it. For psychology to make the moves suggested by the Task Force, there will have to be a very vocal group of psychologists who constantly harrangue the leadership of APA into taking a firm stand. I'd suggest they start up a blog, get in the ears of reporters, and do anything they can to draw attention to their very legitimate concerns. I realize that prescription privileges for psychologists and being corrupted by pharmaceutical marketing are not necessarily one and the same. Only time will tell if psychology will be more strongly influenced by science or by marketing.

Hooked

I have been intrigued with the Hooked blog from Dr. Howard Brody. I had the good fortune of running across the site a few months ago, but I have been doing a poor job of reading it regularly until recently.

Read this post about "intellectual bias" and flacking for Pharma. Also check out this winner of a post regarding academic physicians trying to "ride the tiger" of Big Pharma while still maintaining strong ethical boundaries.

It is about to be added to my blogroll. Good work, Dr. Brody!

Help

I've been informed by multiple readers that my digg, reddit, and other such links in my post footers were not working. How 'bout some help? I cannot, for the life of me, figure out how to make them operational despite trying about 100 different pieces of advice from various sources all across the wonderful world of the internet. Just add your tips in the comments section, please.

Seroquel for Everything and Academic Spokespeople

Part 1. Seroquel for Depression and Anxiety. AstraZeneca is slowly rolling out the PR for Seroquel as a treatment for depression and generalized anxiety disorder. At something called the 7th International Forum on Mood and Anxiety Disorders, AstraZeneca (via academic frontman Stuart Montgomery) has trotted out data from their latest clinical trials which purportedly show that Seroquel beat placebo for depression and GAD. Here's a quote from the detached, independent, non-conflicted academic author, Stuart Montgomery...

Dr. Stuart Montgomery, Imperial College School of Medicine, University of London and author of the [depression] monotherapy study, said: These study results are remarkable -- all of the doses of SEROQUEL XR examined provided improvements in MDD and GAD symptoms. Results from further studies that are still ongoing will add to our understanding of SEROQUEL XR in these conditions.

What is remarkable is not that 'Quell had a slight advantage over placebo but that an "independent" academic psychiatrist is willing to pimp Seroquel so blatantly. It would appear that Dr. Montgomery is aware of who is putting butter on his bread. Finding a modest to perhaps moderate advantage for a drug over a placebo in treating depression and/or anxiety is far from remarkable, given that there are dozens of drugs and psychotherapies that have demonstrated similar or better efficacy. Then again, it is remarkable that Seroquel is related to increased risk of diabetes (1, 2, 3, 4), which is likely not the case for competing depression treatments. Of course, since the movement has now started to treat depression with antipsychotics (1, 2), perhaps we will see many people with depression moving toward an increased risk of diabetes. It might be worth noting that on the MADRS, which was the measure of depression reported in the press release, one question is regarding eating -- the more you eat, the better your score. So an antipsychotic linked to weight gain is set to do well in that those who eat a lot will score better on this item, which is then taken as a sign that they are less depressed.

I've been tracking the Seroquel for everything bandwagon for some time now (1, 2, 3, 4) and I can't wait to see where this is headed next.

Part 2. The Academic Salesperson. As Krusty the Klown might say, "I heartily endorse this event and/or product"...

Here are some other Stuart Montgomery quotes from press releases:

Agomelatine

"Agomelatine is an interesting and potentially very valuable antidepressant that is effective in both moderate and severe depression", says Professor Stuart Montgomery from the Imperial College School of Medicine in London. "The new agent has a unique mode of action, improves sleep without affecting daytime alertness and its efficacy is not compromised by sexual side effects, tolerability problems or discontinuation symptoms.

Escitalopram (Lexapro)

"These results are important because they show we have a treatment at our disposal which is effective without sacrificing the good side-effect profile obviously preferred by patients," commented study author Professor Stuart A. Montgomery, Imperial College School of Medicine, London, United Kingdom. "The ideal combination for any first line treatment is good efficacy and good tolerability - this study shows that escitalopram has all the potency of the non selective SNRIs combined with the good tolerability of the conventional SSRIs," he concluded.

Lexapro (again)

“This consistent advantage really came out as a surprise,” marvelled Prof Montgomery. “These are shocking data that no one was expecting”. He added: “At that stage we already knew that there was something special about the drug”.

Finally, Prof Montgomery mentioned results coming from further studies that he referred to as “staggering” – these were decisive in establishing Lexapro’s long term effectiveness in treating both GAD and SAD.

One more piece on Dr. Montgomery may be of interest to readers (via The Guardian ):

A leading figure in the world of psychiatry gave a pharmaceutical company advice on how to get its new drug approved while he was sitting on the committee which was deciding the licence application.

An internal memorandum from Pfizer, the world's largest drug company, says Stuart Montgomery would be happy to become a paid adviser and declare an interest to the Committee on the Safety of Medicines (CSM) once the drug, an antidepressant to rival Prozac, had been through the licensing process.

Read the whole article and see what you think.

When Dr. Montgomery or other key opinion leaders with similar conflicts of interest speak, we are supposed to view them as independent expert researchers whose enthusiastic product endorsements are based purely based on science. The manner in which every drug company trot out eager academic spokespeople is a sign that academic medicine has become rotten to the core.

Blast From the Past: Suicide Data Regarding Prozac Buried

This post will document plainly how Lilly and/or the National Institute of Mental Health and/or key opinion leader(s) made data on Prozac and suicide vanish. Poof! A study known as Study X065, published with Graham Emslie as the lead author, differs notably from the FDA report on the data from the same study. In the published paper, there is no mention of suicidal ideation whatsoever. None. However, according to the FDA report...

You can read it on page 19 of the report. It is clearly referencing the X065 study. Yet even a passing mention of suicide is not provided in the published paper. Regarding a different medication, the lead investigator for the X065 study, Graham Emslie, was asked at one point why he was not sharing data showing that Paxil/Seroxat was not an effective treatment for child/adolescent depression. He responded as follows:

I couldn’t talk about it because it was proprietary.

In other words, GSK owned the data, so he could not mention the negative information unless he had their permission. In my humble opinion, this gives the impression of Emslie not being a scientist, but rather a sock puppet for the drug industry. Back to the X065 study. Why wouldn't Emslie, lead author of the study insist that the suicide attempt data be included in the X065 study publication? NIMH theoretically owned the data, as they funded the study, so why wouldn't they make sure to publish such important information? It's one thing to exclude data from two patients on Prozac who had, say, treatment-emergent flatulence, but it is quite another to exclude data on a much more troubling treatment-emergent event such as suicide attempts.

I'm not the first to notice this issue. It was previously mentioned by Jonathan Leo in a letter to the editor in Psychiatric Times. When I see this incidence of hiding suicide data and I think about NIMH's poor attempts at journalism regarding the SSRI-suicide issue, it raises my suspicions regarding whose agenda is being served at the agency.

Whose Opinion Matters? Also of note, yet frequently not mentioned by the SSRI's are terrific for kids crowd is that depression measures completed by the children and adolescents in this study showed no significant improvement versus a placebo. This has nearly always been the case in studies examining SSRIs for child and adolescent depression. Measures rated by clinicians have occasionally found an advantage for SSRIs in youth depression, yet almost never have such effects extended to the youths' perceptions of their depression. Call me crazy, but if we're going to say a treatment is effective for depression, yet the people who are depressed say it does not relieve their depression, shouldn't that raise some suspicion? The authors, however, try to squirm out of this difficult position with the following sentences:

Furthermore, self-reported depressive symptom measurements also showed improvement in both groups, but the between-group differences were not significant. However, given the wide variability of initial child self-reports, these findings are difficult to interpret.

Oh, I get it. When a significant advantage is shown on a measure rated by clinicians, it is not difficult to interpret, but when a drug is not shown more effective than a placebo, well, who knows what that might mean? A very nice attempt at obfuscation on the part of the authors. You'd think this was a drug company funded study -- it hid negative data and obfuscated negative findings -- yet the good old NIMH, with our tax dollars, was behind this work.

But worry not, my friends, the study X065 conclusion, as published in the flagship journal of psychiatry (Archives of General Psychiatry) reads as follows:

These data indicate that fluoxetine 20 mg/d is safe and effective in children and adolescents.

Back to Graham Emslie. He admits to helping to keep GSK's secret that Paxil was not an effective treatment for youth depression and he was the lead investigator on a study in which two suicide attempts appear to have been deep-sixed. His interpretations of research regarding Effexor for (you guessed it) youth depression also seem overly positive, and it seems that he helped to keep data on Effexor for youth depression buried for several years. But, worry not, according to his website, he is "is known internationally for his work in the treatment of pediatric depression." Indeed. I'm comforted to know that we can expect this high caliber of work from high-ranking academic psychiatrists.