The Incredible Vanishing Key Opinion Leader

Charles Nemeroff, former chair of psychiatry at Emory University and key opinion leader extraordinaire has vanished. Not quite vanished from the face of the Earth, but from Medscape CME and now from a Georgia mental health commission. Nemeroff was found to have not disclosed a whole boatload of money he received from Big (and little) Pharma according to an investigation by Senator Charles Grassley. For example, it appears that Nemeroff received about $20,000 in cash from GlaxoSmithKline in one month in exchange for promoting GSK products to his peers.

I have previously written about a number of, um, "interesting" behaviors on the part of Nemeroff, which I recommend you read in order to understand that Nemeroff has, on several occasions, engaged in behavior that certainly appears to have placed the causes of his corporate sponsors over science. Not good for an "independent" researcher.

And now, it seems that Chuck Nemeroff is vanishing. Dr. Bernard Carroll noted that Nemeroff's continuing medical education offerings had vanished from Medscape and offered the following:

Well, good for Medscape. They came in for their share of criticism, here and here, a while back. Now they deserve credit for displaying ethical standards. Meanwhile, we are waiting for another company called CME Outfitters to get the message. Dr. Nemeroff is slated to moderate a raft of new programs for this company in the coming weeks, sponsored by corporations like Pfizer, AstraZeneca, and Ortho-McNeil Janssen. CME Outfitters' logo, after all, is Education with Integrity. Sooner or later the pharmaceutical corporations, like the CME companies, will understand that they are not helping themselves by trotting out a shopworn and sleazy KOL figurehead like Nemeroff for their marketing efforts. And other KOLs who up to now were willing to "wet their beaks" in these CME forums controlled by the Boss of Bosses Nemeroff will now be leery of associating with him.

Well, CME Outfitters is still rolling with Nemeroff. For example, he has an upcoming program called "Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough," which is a scary thought given that he appears to have been pulling data from thin air for a prior CME exercise in which he pimped risperidone as a treatment for refractory depression. Specifically, Nemeroff's presentation claimed that risperidone improved sexual function in a clinical trial, when the published article based on the trial's results said no such thing. In addition, Nemeroff's claim that risperidone had shown efficacy in a short-term study versus placebo for depression was also unsupported. So I'm thinking the upcoming program on antipsychotics for depression might be a fantastic example of marketing beating the crap out of science.

Georgia appointed a commission to address several issues within the public mental health system. They have completed a report. Interestingly...

The final version also does not contain the name of commission member Charles Nemeroff, an Emory psychiatry professor who has been a subject of a U.S. Senate Finance Committee investigation into whether drug company money paid to doctors and academics compromises medical research and scholarship. Nemeroff, an internationally known expert on depression, did not attend recent commission meetings.

But Nemeroff was appointed to the commission with some fanfare. The press release listing Nemeroff's accomplishments is pretty lengthy. The Georgia state legislator who appointed Dr. Nemeroff said, "I am confident that Charles will be an asset to this commission and will serve as a strong advocate for the people of Georgia being served [by] our mental health systems"

Yet Nemeroff was not on the final report. If it weren't for his work on CME Outfitters, I would be worried that we might need to file a missing persons report for Dr. Nemeroff.

Update (12-18-08): The Wall Street Journal Health Blog has two interesting posts on Dr. Nemeroff (1, 2). Read them and feel free to file them under "bizarre."

Treatment Guidelines and GSK's Open Disclosure

Last week, I noted that a recently published article had found that studies favoring GSK's "mood stabilizer" Lamictal tended to get published in medical journals while articles reaching less favorable conclusions tended to remained unpublished. I wrote that "GSK worked the system expertly and it paid off." A reader commented that he thought my characterization of GSK as hiding negative data on Lamictal was inaccurate. I appreciate his well-written critical comments, which are linked here and are partially reproduced below:

Acute Depression - All of the acute depression studies (there were 5 not 3 as you reported) were presented at scientific meetings over the years and were recently published in Bipolar Disorders (Calabrese et al. 2008). Why so long to publish? The paper was rejected twice and took 3 years to get accepted because journal reviewers did not find the data of interest.

I responded via comment that, if his history is accurate, then the reviewers should be flogged. He added that GSK had provided negative Lamictal data to numerous authors who wrote review articles on Lamictal. In some cases, this appears to be true. However, in at least one notable case, either GSK failed to provide the data or the authors completely ignored the negative data. The data here appeared in a 2004 "academic highlight" (i.e., lowlight) in the Journal of Clinical Psychiatry. Of relevance, the article was funded by an "unrestricted educational grant" from GSK. The article bashes antidepressant treatment in bipolar as unsupported by evidence. Then the expert panel of authors/key opinion leaders put together their guidelines for treating bipolar disorder.

The article begins by discussing bipolar depression. Lithium is discussed first and receives a positive review. Then comes Lamictal, GSK's mood stabilizer. They discuss, in detail, the positive results from Calabrese et al. The authors then discuss some positive long-term findings for lamotrigine before moving on to olanzapine and olanzapine/fluoxetine. They conclude that lithium and Lamictal have the best evidence for treating bipolar depression as can be seen here:

Category 1 evidence is the best evidence, so hooray for lamotrigine/Lamictal! But what don't they discuss in their "expert" review of the data? How about two negative studies -- SCA40910 (completed in 2002) and SCAB2001 (completed in 1997) -- GSK titles of studies that both showed negative results for Lamictal in treating depression in bipolar disorder. A reader tracked these down and sent them -- you can find them if you head to GSK's clinical trial registry. Given that these "International Consensus Guidelines" were published in February of 2004, you'd think the authors would have included data from both of GSK's unpublished studies unless:
A. They didn't know about their existence (and why would they unless GSK told them)
B. They knew about them but opted to not include them in this "expert review"

Given that a GSK employee has told me how open and honest GSK has been with their data, I'd be interested in seeing his response as to which of the above he believes took place. Keep in mind that the Journal of Clinical Psychiatry, in which this so-called "academic highlight" appeared is a very widely read journal. According to Google Scholar, this piece has been cited 46 times, many of which have doubtlessly recycled the inaccurate claim that Lamictal is an effective treatment for acute bipolar depression.

The same pattern as usual: Company conducts research, selectively publishes positive results, funds "educational" pieces such as "academic highlights" to paint an overly rosy picture of treatment effectiveness and/or safety, and physicians, based upon the "evidence base" delude themselves into thinking that they are writing prescriptions based on the best scientific data.

Lamictal: Break Out the Shovel

GlaxoSmithKline, manufacturer of lamotrigine (Lamictal), the antiepileptic drug used widely for bipolar disorder, happily hid clinical trial results which found Lamictal was no better than a placebo. Given recent findings about how often pharmaceutical companies selectively push positive results to publication in medical journals while suppressing negative results, this can hardly be considered a surprise. It is nonetheless instructive to examine how the published data on Lamictal paint a much rosier picture of the drug's efficacy compared to unpublished data.

Nassir Ghaemi, a psychiatrist at Tufts University Medical Center, dug through GSK's online database of information, and found that several negative Lamictal studies (studies which failed to show a benefit for Lamictal over placebo on the primary outcome measure) were quietly residing on the site. Why did GSK post such information on their site? Not out of the goodness of their hearts; rather, because they were forced to post data about clinical trial outcomes as a result of a legal agreement. Here's what Ghaemi found in GSK's database:

Acute mania: Two studies compared lithium, Lamictal, and placebo. Both found that Lamictal did not beat a placebo. Neither study was published.

Acute bipolar depression: Three studies were conducted. All three showed negative results. Two were not published. On one study, there was a positive result for Lamictal on a secondary outcome measure, and the results of the study were written to emphasize the positive outcomes, as in stating "Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression."

Rapid cycling bipolar: Two studies were completed; both were negative on the primary outcome. However, one study showed favorable outcomes for Lamictal on several secondary measures. The obviously negative study was not published while the study that showed a number of benefits for Lamictal was published.

Prophylaxis (Prevention of future episodes): Two studies were conducted, both of which showed that patients on Lamictal went longer between episodes than did placebo patients. Both studies were published.

Well, I'm shocked, shocked, that GSK would simply bury a slew of negative data on their product. Who woulda thunk it? So what does this mean for Lamictal? Dr. Ghaemi was interviewed by Dr. Daniel Carlat (of Carlat Psychiatry Blog and the Carlat Psychiatry Report). There were many pieces of Ghaemi's interview that were interesting (see February 2008 issue of Carlat Psychiatry report; sorry, no link available), but the most interesting piece was:

Carlat: My understanding is that you wrote up your discovery of the negative Lamictal data and submitted the paper to some journals. What has been the response?

Ghaemi: I first submitted to JAMA because I knews they were sympathetic to this kind of critique. Their reaction was, "We already publish many papers like this; this is old news; there is nothing new here." They recommended that I send it to a psychiatric journal. So then I sent it to the American Journal of Psychiatry, but they rejected it as well, saying that they were doubtful that this type of negative publication bias was common among other companies marketing medications for bipolar disorder.

Carlat: Do you think there is much suppressed negative data about other drugs?

Ghaemi: It's very hard to get this information. Companies are not required to disclose it. And if they do publish it, they will sometimes delay publication for two or three years, and then publish it in an obscure journal that it less likely to be read.

Ghaemi also did some digging on other drugs used for bipolar disorder and found that negative studies for Seroquel and Abilify were also lurking in the unpublished zone. However, it appears that Lamictal is the worst offender of the bunch. Is it just me, or is anyone else getting flashbacks to GSK's handling of suicide data regarding its antidepressant Paxil?

Thanks to an anonymous reader for helping to track down relevant information on this and an upcoming post on this topic. The forthcoming post will deal with the misleading scientific literature on Lamictal. Key opinion leaders will likely be mentioned. The usual stuff, just on a different drug and plugging in the names of other academics who apparently deemed it acceptable to mislead their fellow physicians about the efficacy of lamotrigine. GSK worked the system expertly and it paid off.

S. Nassir Ghaemi, Arshia A. Shitzadi, Megan Filkowski (2008). Publication bias and the pharmaceutical industry: The case of lamotrigine for bipolar disorder Medscape Journal of Medicine, 10 (9), 211-211

Key Opinion Leader With A Very Short Fuse

Psychiatrist Joe "Short Fuse" Biederman of Harvard University is really in hot water now. The sordid details can be seen in a fantastic article by Gardiner Harris of the New York Times. Here's just one snippet:

In a November 1999 e-mail message, John Bruins, a Johnson & Johnson marketing executive, begs his supervisors to approve a $3,000 check to Dr. Biederman as payment for a lecture he gave at the University of Connecticut. “Dr. Biederman is not someone to jerk around,” Mr. Bruins wrote. “He is a very proud national figure in child psych and has a very short fuse.” Mr. Bruins wrote that Dr. Biederman was furious after Johnson & Johnson rejected a request that Dr. Biederman had made for a $280,000 research grant. “I have never seen someone so angry,” Mr. Bruins wrote. “Since that time, our business became non-existant (sic) within his area of control.”

Mr. Bruins concluded that unless Dr. Biederman received a check soon, “I am truly afraid of the consequences.”

A series of documents described the goals behind establishing the Johnson & Johnson Center for the study of pediatric psychopathology, where Dr. Biederman serves as chief. A 2002 annual report for the center said its research must satisfy three criteria: improve psychiatric care for children, have high standards and “move forward the commercial goals of J.& J.,” court documents said.

And from Bloomberg,

Biederman “approached Janssen multiple times to propose the creation of a Janssen-MGH center,” according to an e-mail from a J&J executive. The center would “generate and disseminate data supporting the use” of Risperdal in children, the e-mail said. Pediatric use was approved by U.S. regulators in August 2007.

Wow. And the plot sickens, er, thickens from there. Normally, being caught with one's hands this deep into the cookie jar would lead me to write a much more blistering piece, but the day job shows no signs of abating in its workload. Fortunately, Philip Dawdy is rolling with the story at Furious Seasons (1, 2).

Let's see if Biederman's defenders can defend him in another op-ed as they did a few months ago. Or maybe we can leave Joe to defend himself. Here's what he said a few months ago when facing criticism:

Biederman dismisses most critics, saying that they cannot match his scientific credentials as co author of 30 scientific papers a year and director of a major research program at the psychiatry department that is top-ranked in the "US News & World Report" ratings.

"The critics 'are not on the same level. We are not debating as to whether [a critic] likes brownies and I like hot dogs. In medicine and science, not all opinions are created equal,' said Biederman, a native of Czechoslovakia who came to Mass. General in 1979 after medical training in Argentina and Israel.

Nope, most of his critics cannot match his credentials of apparently shaking down hundreds of thousands of dollars from Johnson & Johnson. But maybe I just like brownies and he likes hot dogs. Another key opinion leader whose reputation is deservedly shot to shreds. Nemeroff, Biederman, and the list goes on.

Staying Alive

The day job has been merciless lately and promises little relief in the near future. Thanks for the emails. I am surviving and hope to write something here relatively soon (emphasis on relatively).

You Really Can Report Safety Data

A new study concluded that the combination of sertraline (Zoloft) and cognitive-behavioral therapy (CBT) worked better than either treatment alone for children with anxiety disorders. There was even a nonsignificant trend for Zoloft to outperform CBT, which was quite surprising to me. But that's not really the point of this post. The study can be read at the New England Journal of Medicine website.

I'd like to commend the researchers on doing something that is exceedingly rare in psychopharmacology and psychotherapy trials -- they gave a detailed report of adverse events. And we find that a greater percentage of kids showed suicidal ideation on... CBT. It was not a statistically significant difference, but it was nonetheless surprising. Zoloft, however, was related to significantly more disinhibition, irritability, restlessness, and poor concentration than CBT. This may have been a fluke, but two participants on Zoloft had "homicidal ideation" compared to none on CBT. I have bitched several times about missing/mysterious data on adverse events in psychiatric drug trials, and some have also complained that psychotherapy trials do a poor job of tabulating adverse event data. Again, kudos to the study authors for reporting adverse events; imagine if reporting safety data in such a manner was commonly practiced.

Source: J. T. Walkup, A. M. Albano, J. Piacentini, B. Birmaher, S. N. Compton, J. T. Sherrill, G. S. Ginsburg, M. A. Rynn, J. McCracken, B. Waslick, S. Iyengar, J. S. March, P. C. Kendall (2008). Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety New England Journal of Medicine DOI: 10.1056/NEJMoa0804633

Psychiatric Diagnoses: Fact or Fiction?

Below is a guest post from Tim Desmond. I do not necessarily agree with all of the the contents of the post below, but I thought the topic was thought-provoking and controversial, so I have agreed to publish it. Feel free to add comments as you see fit; I will likely add my two cents in the next couple days...

I would like to contribute to the discussion on this blog by summarizing the work of Richard Bentall, psychologist and award-winning author, on psychiatric diagnosis and the DSM-IV. While we may be able to agree that long-term use of neuroleptics should not be the treatment of choice for schizophrenia, or that bipolar disorder is being over-diagnosed in children, I would invite us to question whether 'schizophrenia' or 'bipolar disorder' are valid diagnoses at all. Over the course of his career Richard Bentall has critiqued the medical model of modern psychiatric diagnosis and proposed instead a more personalized symptom-based approach.

The basic question is this: Do people suffer from a finite number of discrete psychiatric disorders/diseases or do people experience varying degrees of human suffering in their own idiosyncratic ways (which include spectrums of sadness, fear, dissociation, etc)? The modern mental health establishment clearly subscribes to the former as evidenced by the structure of the DSM and the theory of 'chemical imbalance.' This belief is so pervasive that even people who claim to disagree with the medical model of diagnosis often think within its terms. For example, the idea that one can be 'misdiagnosed' presupposes that a correct diagnosis could exist. Similarly, saying that schizophrenia is partially caused by psychological factors assumes that 'schizophrenia' is a valid way to group people.

The theory that psychological distress is caused by a finite number of psychiatric diseases can be attributed to Emil Kraepelin, who first published his Compendium of Psychiatry in 1883. Kraepelin believed that the psychiatric patients he treated suffered from diseases analogous to any treated by a practitioner of internal medicine. (Note the common comparison today between psychiatric diagnoses and diabetes forwarded by the pharmaceutical industry.) He said a specific disease process should generate identical symptoms, have identical pathological anatomy and identical etiology (or cause). According to Kraepelin, all that was needed was for these diseases to be discovered in order for diagnosis and treatment in psychiatry to catch up with the rest of medicine. Since it was far beyond the knowledge of his time (or ours for that matter) to find common pathological anatomies or etiologies, he chose to group symptoms. He believed that if he grouped symptoms 'correctly' the people grouped together would be sharing the same underlying disease. They would therefore have the same anatomical problems, the same etiology and respond more or less identically to treatment. He hoped that this kind of systematizing would lead to great advances in the efficacy of treatment.

While Kraepelin's categories have changed over time and grown from 3 to over 200, the basic idea persists to this day – that there are a finite number of discrete psychiatric disorders/diseases people can have and if we were to somehow group symptoms 'correctly' we would have isolated real disorders/diseases.

The problem with this idea is that it is not at all based in evidence. It began as Kraepelin's assumption and he was unable to provide any research in his lifetime to support it. However, it has been an idea so compelling to psychiatrists that they have tried in vain to support it for over one hundred years. In fact, there is a large body of research that directly contradicts this theory.

For example, you would expect that if one doctor diagnosed you with Strep Throat, you would be able to go to any other doctor and get the same diagnosis – and you'd be right. The reason for this is that Strep Throat is a real disease associated with an infection of streptococcal bacteria. You either have it or you don't and there are reliable ways to test if you do.

However, if you are experiencing severe psychological distress and one psychiatrist diagnoses you with "bipolar disorder" there is only a 50-60% chance that the next one you see would give you the same diagnosis. Why is this? Both psychiatrists would have been highly trained in diagnosis, and they would be using the same criteria to make their judgment. So if one says you have PTSD, another says bipolar and a third says brief psychotic disorder, which is the "correct diagnosis?" What do you really have?

Bentall argues the problem is that Kraepelin's main assumption – that there are a finite number of discrete psychiatric disorders – is just not true. You don't have any of those disorders because they are not real. Instead he argues that any psychiatric patient is experiencing a high level of emotional distress that is expressing itself through a range of symptoms and these symptoms can be better understood as extreme expressions of normal human responses to distress.

Bentall advocates for abandoning psychiatric diagnoses altogether. He claims that psychiatry's stubborn attempt to treat mental distress as a medical problem is what has led to its inability to improve treatment outcomes over time. Citing a large body of research, Bentall shows that symptoms from depressed mood to hallucinations can be accounted for psychologically and that doing so is not only more in line with science but more humanizing to patients. Therefore he favors what he calls a 'complaint-oriented' approach in which each patient would be assessed according to his or her unique symptomology. The focus becomes the symptoms themselves and we avoid trying to groups them into arbitrary non-existent disorders. Symptoms can be understood and treated, while disorders cannot because they are not real.

To learn more about Bentall's work, read his 'Madness Explained' which won the British Psychological Society's Book Award.

Author Note: Tim Desmond offers phone counseling and training for therapists through his website at www.coherencecounseling.com

The Latest on Kiddie Bipolar

A recent study in the Archives of General Psychiatry claimed that kiddie bipolar tends to become adult bipolar. I have read the study and have a few comments. First, the authors' main findings:

• Children diagnosed with bipolar went on to have a manic episode 44% of the time.

Let's look at the study sample. Seven to 16 year olds who were experiencing a manic or mixed episode. At 8-year follow up, 54 kids had reached at least age 18. So we're talking about 24 of 54 kids who went on to experience a manic episode as adults. Not exactly a huge sample. As time moves along, there will likely be more kids from this study who experience manic episodes as adults, so it is very much possible that when all 115 kids originally enrolled in this study hit, say, age 30, more than half of them will have experienced a manic episode as adults.

The argument then goes that we must treat child bipolar early and intensely in order to prevent these kids from going on to develop bipolar disorder as adults. So, were these kids receiving treatment? Definitely. These kids received whatever treatment was offered in the community, which doubtlessly included stimulants, mood stabilizers, antidepressants, and antipsychotics. On many occasions, they were probably undergoing some serious polypharmacy driven out of desperation rather than any sort of reasonable evidence base.

So did the treatments work? 88% of people who had an original manic or mixed episode recovered, but 73% of these kids then had a relapse afterward. And if nearly half went on to experience mania as adults, doesn't that mean that treatment was not exactly working very well? At this point, the authors have not reported what treatments were used, but I am willing to bet that the polypharmacy I mentioned above was often in place and that very few of these kiddos weren't receiving regular psychopharmaceutical treatment.

Bipolar was not the only problem facing these kids. 94% had an ADHD diagnosis at some point during the 8-year followup and a similar number had some sort of disruptive behavior disorder diagnosis. So it's not just bipolar. As I've been saying for a while now, bipolar is just the name du jour for kids whose behavior is really, really bad. We used to call it ADHD or conduct disorder and now it's ADHD, conduct disorder, and bipolar disorder just abbreviated as "bipolar," driven by the market reality that there are quite profitable drugs used to oh-so-successfully treat kiddie bipolar. But it seems they can't be working that well if 73% of these kids who recover from an episode end up relapsing.

I would love to write more about how bipolar was diagnosed in these kids, but I've not been able to land a copy of the measure used to make bipolar diagnoses in the study. The authors state that they only counted episodes that met DSM-IV criteria; if I ever find time, I might look at this more closely.

And note that we don't know what happened to the youngest kids in the study (those who started at ages 7 or 8) because none of them were adults at the end of this study. This study did not include anyone younger than 7, so the rash of 4 year olds being diagnosed as bipolar is left unexamined.

Bottom Line: Assuming that the diagnoses were valid, this study makes me think that:

• Kids who show really bad behavioral and emotional problems often become adults with major psychological problems. Not exactly earth-shatteringly surprising.
  
• Treatments for child/adolescent bipolar are not working very well.
  
  

Furious Seasons also has a number of concerns about the study.

APA Membership Rejects Torture

APA Membership Rejects Torture

The American Psychological Association membership recently overrode their leadership (the Council of Representatives) via member vote. After significant grassroots organization by several psychologist organizations, the APA was forced to send out a ballot asking members whether APA members should be allowed to work in settings where detainees were held in inhumane conditions and/or in sites that operate outside of the Geneva Convention. And over 60% of respondents said no to psychologists working in settings where inhumane treatment occurs unless it is in the service of detainees, treatment to military members, or a human rights organization.

Then APA President Alan Kazdin issued a letter to President Bush. The full text is available here. Here's one particularly relevant excerpt:

So now APA has finally caught up with the American Psychiatric Association and the American Medical Association, who have banned their members from participating in such activities for years. Not all psychologists are members of APA, so APA does not have any jurisdiction over their behavior. Additionally, passing a change in policy does not physically stop some individuals, in the name of sadism, peer pressure, or defense of country, from abetting or engaging in torture. Nonetheless, on at least a symbolic level, it's nice to see that the membership of APA stood behind this issue.

Let me clearly mention that I have nothing against psychologists in the military, as the mental health needs of the military and their families is a highly important issue. Another important principle: Do No Harm, including to so-called enemy combatants or whomever else was receiving "enhanced interrogation" from psychologists and others.

APA, of course, has always been against torture in principle, but the position they took against it was a little watered-down for my taste, so I'm glad to see that their stance has, by force of the membership, become more clearly anti-torture. An interesting piece from one of the most prominent advocates of altering APA policy on this matter can be read here. The disgusting work products of some psychologists who actively engaged in torturous practices are described in a rather shocking Vanity Fair article.

And please, oh please, let nobody take the tack that I am some left-wing pro-terrorist nutjob just because I believe that torturing the hell out of people is both unethical and ineffective.

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?"

Uh-Oh Chuck, They Out To Get You, Man

According to the New York Times and Wall Street Journal, it looks like Charlie "Bling Bling" Nemeroff is under investigation by Senator Charles Grassley. Gee, I can't imagine why. Maybe because documents indicated that he failed to report over a million dollars of income received from the drug industry? It also turns out that the Chuckster made nearly $3 million in consulting deals with pharma from 2000-2007. That doesn't mean that his behavior was ever influenced by such huge sums of cash, right? Oh, wait just a minute...

...It turns out that there were several incidences of unbecoming behavior involving Bling Bling, I mean, the esteemed Dr. Nemeroff. Who could forget the time that he conveyed what appears to be fictional data in a continuing medical education course? How 'bout an article that seems to overstate the advantages of Effexor (1, 2)? And his contradictory statements regarding the role of serotonin in depression? His involvement in a shady at best study on the effects of Risperdal in depression is also worth reading. In fact, for a summary of many issues regarding Nemeroff, feel free to read an earlier post that outlines many events and provides links for more in-depth information on each of them.

One of my first posts on Nemeroff was presciently titled: Uh-oh Chuck, They Out to Get Us, Man. Apparently, I was foreshadowing the present investigation. Don't feel too bad for Nemeroff; he should be able to afford excellent legal representation.

Maybe this latest mire in which Nemeroff finds himself explains the uptick in hits from Emory University and the Senate this site has been seeing lately?

Please also read Daniel Carlat's unflattering take on Nemeroff's behavior.

Prialt Pushed Through Duplicate Publication

Apparently, the same data on Elan's pain medication Prialt (ziconotide) was published twice. Same data set. No reference in the second publication to the first publication. As I noted last week in a post about Cymbalta, that's not supposed to happen. It's the sort of thing that leads physicians to believe that a medication has a lot of supporting evidence -- "Of course I prescribe it; I've seen two positive clinical trials" -- when in fact it's just the same data being repackaged in another journal. The full story is contained in two posts at The MacGuffin (1, 2). An infomercial passing off as continuing medical education is also involved in the plot. Count The MacGuffin as an official must-read blog.

Gabitril Goes Down

Gabitril (tiagabine) is an antiseizure medication from Cephalon, which just forked out a cool $425 million to settle charges that it marketed several drugs for unapproved conditions, including Provigil and Gabitril. Government investigators claimed that Gabitril was marketed as a treatment for anxiety, which is too bad considering that it struck out in three clinical trials against a placebo. Each study found no evidence that Gabitril was better than a sugar pill.

Gabitril was also allegedly marketed as a treatment for pain. I was unable to locate a single controlled study examining the efficacy of Gabitril for pain, though there were a small number of uncontrolled (i.e., not very useful) studies suggesting that maybe Gabitril could be used to treat pain. Regarding sleep, the placebo-controlled trials I located did not suggest that the drug was particularly effective (1, 2). So we're looking at a drug with essentially no controlled evidence of efficacy being pushed for pain, sleep, and anxiety. Well-done, Cephalon.

Some of the supporting evidence about the off-label marketing cases came from a sales rep who wore a wire to collect evidence on the company's marketing practices. Apparently a total of four company whistleblowers were involved. Shades of Peter Rost?

Read more about the case at the Philadelphia Inquirer.

PS. Cephalon published the negative anxiety Gabitril trials in June 2008. As is well-established, companies often fail to publish negative data about their products, so why is Cephalon being so open? A skeptic might note that with the legal case againt Cephalon gaining steam, it would look even worse if Cephalon was sitting on negative data. So perhaps knowing that bad publicity was coming due to the lawsuit led Cephalon to allow the negative anxiety results to be published, as they could state "Look at how open and honest we are." I'm just saying that it's a possibility.

Reference for anxiety trials:
Mark H. Pollack, Jane Tiller, Fang Xie, Madhukar H. Trivedi (2008). Tiagabine in Adult Patients With Generalized Anxiety Disorder Journal of Clinical Psychopharmacology, 28 (3), 308-316 DOI: 10.1097/JCP.0b013e318172b45f

Update: Also read a related post at Health Care Renewal. It mainly discusses Cephalon's opiate-laced "perc-o-pops" (Actiq) approved to treat cancer pain, but marketed in a much broader manner.

Follow-up mini-rant: Let's not excuse the physicians who jumped on board. Docs need to do a much better job of checking the evidence base, though when some of the evidence base consists of publishing the same data repeatedly and when negative trials are often not published, what kind of "evidence base" are we really talking about?

The Cymbalta Schatz-Storm: Duplicate Publication and Lying by Omission

This post details the duplicate publication of data on the antidepressant duloxetine (Cymbalta). Marketing and "science" collide to produce hideous offspring: an experimercial that pimps Lilly's bogus "Depression Hurts" marketing for Cymbalta using the exact same (weak) data twice. Data were published in the Journal of Clinical Psychiatry (JCP), and then the same data were published a second time in the Journal of Psychiatric Research (JPR), a blatant violation of JPR policy. Oh, and Alan Schatzberg, president-elect for the American Psychiatric Association is involved in the story.

The study: Lilly conducted a rather uninteresting study of Cymbalta, in which patients who had not shown a treatment response to an SSRI were then assigned to either a) Direct switch: Switch to Cymbalta and immediately discontinue the SSRI medication or b) Start-Taper-Switch: taper the SSRI over a 2 week period while also starting Cymbalta. Note that there was not a control group of any sort, an issue that the authors dance around (i.e., essentially ignore) in the papers based on this study's data.

Publication #1 -- Journal of Clinical Psychiatry: Data from this study were published in the January 2008 issue of the Journal of Clinical Psychiatry. The findings were that, in essence, there were no notable differences between patients who were directly switched to Cymbalta as opposed to those who did the start-taper-switch method. But what do the authors conclude?

Despite the lack of control group, the authors get the message out that not only was depression improved, so were "painful physical symptoms." As anyone who has a television has probably noticed, Lilly has been pushing hard for quite some time to convince patients and physicians that Cymbalta will relieve depression and pain in depressed patients. So if the marketing points can be pushed in one journal, why not pimp the same idea using the same data in another journal?

Publication #2 -- Journal of Psychiatric Research: Data from the same study were published online (to appear in print soon) in the Journal of Psychiatric Research (JPR). And I mean the exact same data appear again in this paper. This is a huge scientific no-no. Findings are supposed to be published once, not over and over again. Journals are struggling to find space for new and interesting findings, so there is no need to waste space on duplicate data. In fact, to quote from JPR's website

Submission of a paper to the Journal of Psychiatric Research is understood to imply that it is an original paper which has not previously been published, and is not being considered for publication elsewhere. Prior publication in abstract form should be indicated. Furthermore, authors should upload copies of any related manuscript that has been recently published, is in press or under consideration elsewhere. The following circumstances indicate that a paper is related to the manuscript submitted to the Journal: a) any overlap in the results presented; b) any overlap in the subjects, patients or materials the results are based on.

So it's pretty clear -- don't submit data that has already been published. Here is a figure from the Journal of Clinical Psychiatry (JCP) article mentioned above:

And here is the same data, in a figure in JPR:

But wait -- that's just the beginning. How about the data tables... From JCP:

And the right-side half of this table in JCP:

And the exact same data appearing in JPR:

To be fair to these "researchers" in JPR, they reported data from subscales of two measures not reported in JCP. But the vast majority of the data is just reprinted from the article in JCP. Which is completely trouncing journal policy and, more importantly, conveying Lilly's marketing messages to the audiences of two different journals. Unfortunately, they apparently did not consider that some people might actually read both journals and notice that essentially the same article had appeared twice. Or, Lilly considered this prospect and said, "Who cares." I'll leave it to my readers to decide if they care.

Authors: The JCP paper was authored by David Perahia, Deborah Quail, Derisala Desaiah, Emmanuele Corruble, and Maurizio Fava. The JPR paper was "authored" by Perahia, Quail, Desaiah, Angel Montejo, and Alan Schaztberg. So to re-publish the same data, it was out with Corruble and Fava -- in with Montejo and Schatzberg. Why Schatzberg? We're almost there...

JPR describes the contributions of each author. For these two authors (Schatzberg and Montejo) who were not credited in the JCP paper, they were both described as "involved in data review and interpretation, including the development of this manuscript." How could they have been involved with data review and interpretation -- the vast majority of the data were already analyzed, interpreted and written up by other researchers in the JCP paper? Did they write the paper? Apparently not, since the JPR article mentioned that "Dr. Desaiah worked with Dr. Perahia to draft the manuscript..." So Montejo and Schatzberg could not conceivably have played any significant role in data analysis, interpretation, or writing the paper. It seems that if Desaiah and Perahia "drafted" the manuscript, then the most Montejo and Schatzberg could have done is to maybe review the paper.

So why is Schatzberg on the paper? Well, it just so happens, I'm sure by sheer coincidence, that Schatzberg is the co-editor in chief of JPR. So he'd be in a good position to help a paper that essentially republishes data from JCP with only minor additions make it into publication against his own journal's policies.

Nice work, Schatzberg. That's pimpin' it hard. That, my friend, is worthy of nomination for a coveted Golden Goblet Award. Congratulations. It is not the first time Schatzberg's "scientific" behavior has been noted. He has been stumping (in the face of much contradictory data) in favor of his pet drug RU-486/Corlux in the treatment of psychotic depression for some time. Between the bad science surrounding Corlux and Schaztberg's myriad conflicts of interest, much has been written (1, 2, 3, 4, 5) -- add another chapter to the chronicles of the storied American Psychiatric Association Leader. This reminds me of an earlier incident involving Charles Nemeroff.

Discussion: As I've noted previously, the discussion section of a journal article often contains key marketing points, science being relegated to secondary status at best. The JPR article provides a few good examples of Cymbalta's talking points:

The current paper focuses on pain-related outcomes, demonstrating that a switch of SSRI non- or partial-responders to duloxetine was associated with a significant improvement in all pain measures including six VAS pain scales, the SQ-SS and its pain subscale, and the SF-36 bodily pain domain.

Switch of SSRI non- and partial-responders to duloxetine resulted in mean improvements on all pain measures regardless of the switch method used.

Duloxetine, an SNRI, has previously been shown to be effective in the treatment of PPS associated with depression, and it is also effective in the treatment of chronic pain such as diabetic peripheral neuropathic pain (DPNP) for which it is approved in the US, Europe and elsewhere, so duloxetine’s effects on pain in our sample of SSRI non- or partial-responders was not unexpected.

Patients with MDD present with a broad range of symptoms including those related to alteration of mood and PPS, all of which may contribute to global functional impairment. Effective treatment of both mood symptoms and PPS associated with depression may therefore optimize the chances of functional improvement. Recent findings that residual PPS in depressed patients may be associated with impaired quality of life (Wise et al., 2005, 2007), decreased productivity and lower rates of help seeking (Demyttenaere et al., 2006) and a lower likelihood of attaining remission (Fava et al., 2004), further demonstrate the importance of effective treatment of PPS in patients with MDD, so duloxetine’s effects on PPS are reassuring.

Improvements in pain are consistent with previously reported studies demonstrating duloxetine’s efficacy for pain, either as part of depression, or as part of a chronic pain condition such as DPNP.

Where do I start? How about by mentioning that JPR states:

7. Discussion: The results of your study should be placed in the appropriate context of knowledge, with discussion of its limitations and implications for future work.

So maybe if there was research that questions Lilly's talking points about Cymbalta relieving pain in depression, such research should be discussed. Well, it just so happens that there is research, which analyzed Lilly's own clinical trials and found that Cymbalta was no better than a placebo or Paxil in treating pain in depression. This meta-analysis of Cymbalta trials was published in January 2008, yet the JPR article, which was originally received by JPR on March 26, 2008 did not mention the negative data. Hmmm, that doesn't exactly sound like placing the findings "in the appropriate context of knowledge," does it? All this talk about Cymbalta's fantastic analgesic effects despite Lilly's own data showing that Cymbalta is at best close to useless in treating pain among depressed patients. Another study that claimed to show Cymbalta was a helluva painkiller was also smacked in a letter to the editor a few months ago -- and the authors of the Lilly-sponsored trial conceded defeat by refusing to reply to the critiques of their study.

Better Than "Weak" SSRIs (Not Really): In the JPR study, it was mentioned that the evidence for SSRIs in treating pain is "weak." No disagreement on my end. But see, once SSRI patients switched to Cymbalta, their pain magically went away because Cymbalta, unlike SSRIs, relieves pain. Never mind the lack of control group, which was allotted a grand total of 15 words in the discussion as a potential limitation of the study. The authors also failed to note that prior research showed that Cymbalta was no better than Paxil in treating pain in depressed patients. And Perahia, the lead author of the JCP and JPR "studies" is certainly aware of the research showing that Cymbalta works no better than a "weak" SSRI, since he was the lead author on one such study! So he is quite aware that Cymbalta has never been shown superior to Paxil in treating pain, yet he accurately describes research indicating that SSRIs are "weak" pain treatments, but then neglects to mention that Cymbalta failed to demonstrate superiority to Paxil in treating pain in depression. This is called lying by omission.

I may pass along my concerns to the Journal of Psychiatric Research. My prior experiences in passing along such concerns to journals via my blog identity is that they either a) ignore my concerns entirely or b) instruct me to write a letter to the editor which would be considered for publication, with the stipulation that I use my real identity. Sorry, but a published letter to the editor is not worth blowing my cover.

Call for Action: Rather than my running into point b. from the last paragraph, how about one or more scientifically inclined readers submit your concerns to the journal, under the following condition: Make sure you read the original papers first to judge if my concerns are valid. Then, if you feel similarly, why not send a letter to the editor? This is bad science which does nothing to advance patient care -- it seeks only to advance sales of Cymbalta by pimping it as a painkiller in depression while ignoring all contradictory data. So let's try a little research of our own -- see if JPR is willing to address these issues or if they will be swept under the rug.

Reference to JPR article:

D PERAHIA, D QUAIL, D DESAIAH, A MONTEJO, A SCHATZBERG (2008). Switching to duloxetine in selective serotonin reuptake inhibitor non- and partial-responders: Effects on painful physical symptoms of depression Journal of Psychiatric Research DOI: 10.1016/j.jpsychires.2008.07.001

Update: Also see an excellent follow-up post on the topic at Bad Science.

Dear American

As for our latest economic crisis, I couldn't resist stealing this from Angry Bear:

Dear American:

I need to ask you to support an urgent secret business relationship with a transfer of funds of great magnitude.
I am Ministry of the Treasury of the Republic of America. My country has had crisis that has caused the need for large transfer of funds of 800 billion dollars US. If you would assist me in this transfer, it would be most profitable to you.
I am working with Mr. Phil Gram, lobbyist for UBS, who will be my replacement as Ministry of the Treasury in January. As a Senator, you may know him as the leader of the American banking deregulation movement in the 1990s. This transactin is 100% safe.
This is a matter of great urgency. We need a blank check. We need the funds as quickly as possible. We cannot directly transfer these funds in the names of our close friends because we are constantly under surveillance. My family lawyer advised me that I should look for a reliable and trustworthy person who will act as a next of kin so the funds can be transferred.
Please reply with all of your bank account, IRA and college fund account numbers and those of your children and grandchildren to wallstreetbailout@treasury.gov so that we may transfer your commission for this transaction. After I receive that information, I will respond with
detailed information about safeguards that will be used to protect the funds.
Yours Faithfully Minister of Treasury Paulson

Doing Some Digging

Some good material is coming. Unfortunately, it involves the same old people doing the same old tricks. But the scandal factor is reasonably high, so I assure that regular readers will not be disappointed.

In the meantime, check out another hot, hot psych blog: The MacGuffin. This fellow anonymous mental health blogger hates bad science. We're peas in a pod that way. And he's willing to diss research on both psychotherapy and meds. Dripping with sarcasm and with a sharp eye for spotting scientific shortcomings, I wholeheartedly encourage all readers to add the site to your list of faves.

Also, Danny Carlat is continuing to get into scrums with the CME industry and it's fun to read about.

Furious Seasons updates us on the FDA and child bipolar disorder.

As per usual, the Scientific Misconduct Blog has items related to scientific misconduct. Questions surrounding the behavior of a so-called regulatory agency and drug safety are brought to the fore yet again.

Findings from my latest investigations will hopefully be unveiled soon. Stay tuned!

Big Drugs, Small Brains?

I've read on and off about brain shrinkage being linked to antipsychotics. I have not paid a lot of attention to research on the topic but kept it on my mental backburner. And now Furious Seasons notes that Nancy Andreasen is reporting that her research shows antipsychotics are strongly linked to brains getting smaller. The longer one takes these drugs, the smaller the brain. Does anyone want to set up a YouTube "This is your brain on drugs" video?

Interestingly, a group of researchers has claimed that olanzapine (Zyprexa) has "neuroprotective" qualities; it's good for your brain. Um, color me skeptical. Their research was based on rats, whereas Andreasen's work is on humans. Andreasen's latest work is not yet published, making it difficult to judge the quality of the findings. But research on monkeys exposed to antipsychotics found that:

In conclusion, chronic exposure of non-human primates to antipsychotics was associated with reduced brain volume.

I am not a neuroscientist, but if both sets of findings were accurate, then we'd have people taking antipsychotics who have smaller but better brains. The more neuroscientifically inclined may wish to comment on this possibility, because it seems a little odd to me.

Bipolar Overawareness Week: New York Times Magazine Edition

Jennifer Egan has a roughly 29,000 word piece in the New York Times magazine regarding child bipolar disorder. OK, maybe it just seemed that long. As is apparently required for such articles, there is a very lengthy story about an allegedly bipolar child that constitutes much of the article. I'll not be focusing on that. Instead, I'll be looking at how the article discusses the controversy surrounding the diagnosis. Quotes from the article followed by my comments follow:

The Diagnostic and Statistical Manual of Mental Disorders (the current edition is referred to as D.S.M.-IV) describes bipolar disorder as a condition whose average age of onset is 20, but virtually all the leaders in the field now say they believe it exists in children too.

Well, then. I found two psychiatrists whose opinion appears to differ. Jon McClellan seems to disagree that bipolar exists in young children, as does David Healy. I could probably find others without much difficulty. Maybe they are not "leaders in the field?" But ok, let's say that it does exist in young kids. I'll grant Jennifer Egan that most agree that bipolar exists in adolescents (but toddlers???), though at what rate is a matter of debate. And more importantly, who gives a rat's behind what people think? Um, maybe we should be more concerned about what the actual science has to say about it. And in that regard, there are some serious unanswered questions, as I've described before.

1. Does child bipolar really exist in substantial quantity?
2. Does treatment help kids with this "disorder"?

But to be fair to Egan, maybe I took the last quote out of context, because she adds a somewhat more balanced view by stating that:

Many clinicians say the illness looks significantly different in children than in adults, but the question of how it differs, or what diagnostic terms like “grandiosity,” “elevated mood” or “flight of ideas” (all potential symptoms of adult bipolar disorder) even mean when you’re talking about kids, leaves room for interpretation. For example, it’s normal for children to pretend that they are superheroes, or believe that they can run faster than cars, whereas in an adult, these convictions would be signs of grandiosity. Equally unclear is whether a child who is identified as having a bipolar disorder will grow up to be a bipolar adult. Work on the D.S.M.-V is under way, and discussions have begun on how to address the issue of bipolar children.

As Ellen Leibenluft, who runs the pediatric bipolar-research program at the National Institute of Mental Health, told me, “There definitely will be — and needs to be — more description of what bipolar disorder looks like in children, how one diagnoses it and some of the challenges.”

OK, that's better. But in general, the article focuses on the proponents of the child bipolar paradigm rather than those who raise concerns. And Egan discounts a big study in a pretty odd way...

A study last fall measured a fortyfold increase in the number of doctor visits between 1994 and 2003 by children and adolescents said to have bipolar disorder, and the number has likely risen further. Most doctors I spoke with found the “fortyfold increase” misleading, since the number of bipolar kids at the beginning of the study was virtually zero and by the end of the study amounted to fewer than 7 percent of all mental-health disorders identified in children.

Huh? So it's misleading to say that for every one treatment visit for bipolar in 1994, there were 40 in 2003? No, that's exactly what the study found. Let's try an analogy. The rate of suicide among kids and teens, on an absolute scale, is very low. Very few children and adolescents actually commit suicide. So if the suicide rate went up by a factor of 40 in the next 10 years, would we then say, "Well, that's misleading because suicide was very rare in 2008, when the study began?" That makes no sense whatsoever. And to say, hey bipolar is now only 7% of kids diagnosed with mental disorders, so it's no big deal -- ??? What treatments do you think these kids get? Play therapy and lollipops? Uh, try antipsychotics, often in combination with anticonvulsants, antidepressants, and who knows what else? If you think this is all based on science, go take a spin over to Pubmed and see what you can find. What, there's no evidence that carpet bombing developing brains with a wide variety of psych drugs is effective for "bipolar"? Count me as shocked, shocked, that medications would be prescribed so widely in the absence of supporting evidence. Sure, maybe if you provide highly tranquilizing medications, they mellow out bad behavior a bit in the short-term. Is that an effective long-term solution? And at what cost?

In Leibenluft’s studies at the National Institute of Mental Health, only 20 percent of children identified with bipolar disorder are found to meet the strict criteria for the disease. Breck Borcherding, a pediatric psychiatrist in private practice in the Washington area, said: “Every time one of my kids goes into the hospital, they come out with a bipolar diagnosis. It’s very frustrating.”

OK, so a study that finds that bipolar diagnoses have shot through the roof is "misleading," but at the same time, other Egan then discusses research suggests that bipolar is being misdiagnosed at a high clip. Am I the only one who is confused?

Then there is “The Bipolar Child,” a successful book published by the psychiatrist Demitri Papolos and his wife, Janice, in 1999, and referred to by more than one parent I spoke to as a “bible.” The Papoloses’ description of pediatric bipolar disorder was amassed partly by using responses to an online questionnaire filled out by hundreds of parents on an electronic mailing list, who said they believed their children were bipolar (and who often had strong family histories of the disease). The Papoloses’ diagnostic criteria include some idiosyncratic items — a severe craving for carbohydrates, for example — that are found nowhere in D.S.M.-IV. Nevertheless, many parents walk into doctors’ offices having already read “The Bipolar Child” and concluded that their children are bipolar. Because doctors rely heavily on parental reports when diagnosing disorders in children, these “prediagnoses” may have an impact on the outcome.

Well, if that isn't the most airtight method for a study that I've ever heard. Put up an online questionnaire, have people who insist that their kids are bipolar fill it out, then use whatever these parents say as criteria for the disorder. And... severe craving for carbs? Nope, I've never ever seen a kid who really, really wants candy before. But if I do see such behavior, I'll turn on my bipolar radar; I'll be keeping my eyes peeled at the candy store.

And of course, there are pressures and blandishments from the pharmaceutical industry, which stands to profit mightily from the expensive drugs — often used in combination — that are prescribed for bipolar illness, despite the fact that very few of these drugs have been approved for use in children.

You mean like the part where key opinion leaders sign on for Big Bucks to give talks for psych drugs in treating kiddie bipolar? No, you won't find discussion of that anywhere in the article. Because we are making progress in understanding the biological disease of bipolar disorder and how to treat it. Progress is slow but everything is headed in the right direction -- the time-honored narrative of the academic-pharmaceutical complex always making progress in mental health. There is a sentence dedicated to discussing the influence of Big Pharma. One. Off-label marketing of antipsychotics for kids is never mentioned, despite Otsuka/Bristol Myers Squibb settling a federal lawsuit for pimping Abilify for kids. I suppose mentioning such shenanigans might poke a bit of a hole in the idea that we are making perpetual progress.

And here comes the hammer. Sure, bipolar might be overdiagnosed, but of course the biggest problem is the undertreatment of bipolar kids:

For all the possible overdiagnosing of pediatric bipolar disorder, however, many in the field also say that a lot of truly bipolar children who could benefit from therapy are falling through the cracks. This is a critical issue; studies clearly show that the longer bipolar disorder goes untreated, the worse a person’s long-term prognosis.

If you are so into "studies clearly showing" things, then maybe you could point to studies that clearly show benefits of treating bipolar disorder in children. I'm waiting. In fact, I've been waiting for years. As the rate of drugging kids for bipolar has increased drastically, the research showing treatment benefits is... where? And if you're telling me that kids behaving very badly, which seems to be fit roughly 100% of kids who wind up diagnosed with bipolar disorder, are not getting treatment, I think you aren't paying attention. Desperate parents want a solution, and whether the diagnosis is opposition defiant disorder, conduct disorder, ADHD, autism, pervasive developmental disorder, WTF NOS, or bipolar, I'm pretty sure that these kids are getting treated in droves. But maybe I'm wrong.

Gabrielle Carlson, the director of child and adolescent psychiatry at the Stony Brook University School of Medicine, has studied childhood mania for many years and says bipolar disorder is uncommon in children under 10, revealing itself in the same discrete episodes of mania and depression that we see in bipolar adults — not in chronic irritability. According to Carlson, a large group of aggressive and explosive children, who in fact are “diagnostically homeless,” are being relabeled as bipolar, which is a development she says is unhelpful both to the children and the field. “Diagnostically it ends up being a very important consideration of what the kid really has,” she told me. “If he really has A.D.H.D. and it’s not mania, then you give him medication for his A.D.H.D. You also give him behavior modification.” One patient she saw that day, who was thought to have bipolar disorder, actually had autism, she said. “If you say, ‘Hey, his problem is bipolar disorder,’ then you’re not going to treat his language disorder, you’re not going to give the social-skills treatment he needs,” she said. Problematic conditions in a child’s home life are also less likely to be addressed if the child’s behavioral issues are attributed to bipolar disorder, Carlson said. “Many people, when they hear bipolar disorder, their brain slams shut.”

After including quotes from Janet Wozniak of the ever-present Harvard bipolar child team, it was nice to see comments from someone who has a bit more skepticism. A harsher critic could have been included in the story, but was not. No, I'm not going to quote Wozniak because you already know what she said, which is that we discovered that bipolar disorder in kids is way, way, way, way, more common than previously thought.

The most basic question about bipolar kids remains a mystery: Will they grow up to be bipolar adults?

No, four of the most basic questions are, in no particular order:

1. How many of these kids labeled as bipolar have been misdiagnosed?
2. What are the benefits and risks of treatment, in the short-term and in the long-term?
3. What happens if we try nonmedical interventions aimed at changing discipline strategies, proving more structure at home, etc.
4. Is child bipolar at least partially a medical term for bad behavior? And where does the bad behavior stem from? Could social problems have anything to do with it? Think of things like poverty, absent parenting, violent TV programming and video games, vastly unequal income distribution, gangs, unemployment/underemployment, and the list goes on... In other words, our society ain't exactly ideal and some of these problems will impact mental health. Isn't throwing pills (or even therapy) at these problems a little shortsighted? This ain't the place to discuss how to improve society; I'm just saying that many of these problems discussed on the site probably arise from more than just intrapsychic issues or troubles with an alleged (not proven) "chemical imbalance." Do you think there is a reason, for example, that foster kids are so frequently on antipsychotics? As written by The Last Psychiatrist: "A 20% increase in therapy visits will be interpreted by psychiatry as a 20% increase in depression and anxiety. It will say depression has a prevalence of X, it will say it is underdiagnosed and undertreated, etc. And it will creep into the social consciousness that these are pre-existing diseases with triggers, not the consequences of external events. Society needs that illusion, it needs that lie, because it has created unrealistic expectations in people and no way of fulfilling them."

Think my question 4 is a little weird, that it's wild speculation? Well, if you want some wild speculation that exceeds mine, try a few slices from the NYT mag piece:

Some studies suggest that bipolar disorder may actually be on the rise among young people. One intriguing hypothesis involves a genetic phenomenon known as “anticipation,” in which genes become more concentrated over generations, bringing a stronger form and earlier onset of an illness with each successive generation. Another theory is “assortative mating,” in which a more mobile and fluid society, like ours, enables the coupling of people whose mutual attraction might be partly due to a shared genetic disposition to something like bipolar disorder, thus concentrating the genetic load in their offspring.

Yeah. That's the ticket. We've had how many thousands of generations of human existence and now, suddenly, bipolar is becoming more concentrated in kids. Intriguing hypothesis? Wouldn't such a trend be gradual, not sudden? Same story with "assortative mating" -- is it just now that bipolar folks would choose to mate with each other? Presumably, this would have happened throughout human existence, so pulling this kind of thing out of a hat now makes absolutely no sense. But there's an answer to that -- we're living in a "more mobile and fluid society." So now that we're "mobile," bipolar folks breed with bipolar folks, but before cars and planes, they couldn't breed with each other. Huh?

Kiki Chang, director of the pediatric bipolar-disorders program at Stanford, has embraced the kindling theory. “We are interested in looking at medication not just to treat and prevent future episodes, but also to get in early and — this is the controversial part — to prevent the manic episode,” he told me. “Once you’ve had a manic episode, you’ve already crossed the threshold, you’ve jumped off the bridge: it’s done. The chances that you’re going to have another episode are extremely high.”

Oh boy. Preventive psychopharmacology. If you are a hyper kid, we'll give you antipsychotics because they might keep you from becoming bipolar later. Trust us, your son is fine in our hands, ma'am.

Also see Furious Seasons' take on the matter. And give him some $$$ to help with his fundraiser. If you ever wanted to give me money, don't. Pass it his way.