Is the credibility of Emory neurologist Helen Mayberg in question? You judge

A few weeks ago, I blogged about the strange case of Dr. Helen Mayberg, a neurologist at Emory University who has testified in more death penalty cases in recent years than almost any other doctor in the country. I highlighted Mayberg's lucrative and lethal (she always testifies for the prosecution who are pushing for the death penalty) sideline as an example of why the National Institutes of Health should adopt stricter conflict of interest guidelines that would require universities to more fully disclose the extent of their researchers' financial conflicts of interest.

At the time, I quoted a prominent neurologist who said that Mayberg goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process. Since then, I have received additional information about her testimony in one particular death penalty case that appears to buttress such accusations. Indeed, critics say that her testimony indicates a level of hypocrisy and willingness to dissemble that should concern officials at the NIH, where Mayberg is principal investigator of several major multi-million-dollar research grants.

First some background. As I've blogged about here, Mayberg was recruited to Emory University by former psychiatry kingpin Charles Nemeroff and soon became involved in a major conflict of interest controversy with Nemeroff when they both failed to disclose significant financial ties to a medical device company in a positive paper they wrote about the company's patented technique. After Nemeroff was forced to step down as chief of psychiatry at Emory (for this and other failures to disclose), he departed Emory for the University of Miami. And lo and behold, Mayberg, who is not a psychiatrist and has never treated patients in clinical practice, became principal investigator of two major NIMH studies Nemeroff used to lead: the mood and anxiety disorders initiative, a collaboration between NIMH (which put up $2.1 million last year alone) and GlaxoSmithKline, to develop a new generation of antidepressants, and another $1.8 million study called predictors of antidepresssant treatment response.

As the principal investigator of such large, taxpayer-funded studies, Mayberg's credibility should be above reproach. However, according to transcripts, she has testified under oath in direct contradiction of her own statements in published research papers. In one particular death penalty case, a neurologist for the defense testified that PET scans taken of the defendant, a guy convicted of murder by the name of Erick Virgil Hall, showed that he had decreased functioning in an area of the brain associated with impulse control and aggressive behavior. Dr. James Merikangas, a clinical professor of psychiatry and at the George Washington School of Medicine, used the neuroimaging results, together with a comprehensive review of the defendant's social and medical history and a physical examination, to conclude that Hall had brain damage that should be allowed as mitigating evidence in his case. Merikangas was careful not to say that the decreased brain functioning found in the PET scan explained Hall's violent behavior, only that there was evidence of brain damage that may have impaired his judgment. (Such mitigating evidence is often introduced in an effort to take prisoners off death row and convert their sentence to a life in prison).

In her 2007 testimony in the Hall case, Mayberg derided the value of PET scans in showing brain damage, saying that "the use of PET scans for the clinical diagnosis and treatment of individual patients is extremely limited." She concluded that PET and functional neuroimaging scans cannot be used for diagnostic purposes or to quantify "residual effects of past traumatic brain injury."

However, Mayberg herself has used PET scans to diagnose depression and evaluate the response of depressed patients to deep brain stimulation, a surgical technique that she developed and patented and continues to promote as a valid treatment for depressed patients who have not responded to drugs; I've blogged about the controversial nature of her work here. In several papers Mayberg published about her research with deep brain stimulation, she discussed the value of using PET scans for this purpose. In one 1990 paper, for instance, she said that a PET scan "showed hypometabolism [decreased brain functioning] in the right lateral basotemporal region in all three patients." In another 2007 paper, she used PET scans to assert that "non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex." In yet another summary of one of her NIH-funded studies, she says she will use PET scans to assess the response of patients to different treatments. In these and other published articles, Mayberg herself is drawing cause and effect relationships between brain abnormalities and specific psychological conditions.

As Merikangas points out in his affidavit, Mayberg is well aware of the importance of neuroimaging in a forensic setting. In another 2007 paper, Mayberg concluded:

"In sum, neuroimaging evidence has become an increasingly important tool of proof in criminal and civil cases in the United States. Although subject to the constraints of reliability and relevance, results of neuroimaging scans can and do help courts to understand the nature, causes and behavior implications of injuries to the brain."

Indeed, a recent study cited in the New York Times affirmed that a highly sensitive functional type of magnetic resonance imaging found evidence of brain injuries in veterans injured in Iraq or Afghanistan that was too subtle to be detected by standard MRI scans.

To be fair, Mayberg testified in the Hall case three years before this new study came out. However, by 2007, plenty of research evidence existed showing that PET and other neuroimaging scans could detect key changes in brain functioning. In his affidavit, Merikangas cites three papers published in 2005 and 2007 indicating decreased brain functioning picked up by PET scans in areas implicated in aggressive and violent behavior.

Mayberg, Merikangas says, is simply ignoring the peer-reviewed literature on this subject. He concludes that her testimony in the Hall case is both misleading and deceptive. Now, Mayberg is at liberty to consult for and testify in whatever legal proceedings she elects to, as long as she fully discloses these conflicts of interest (which some would argue she hasn't). But as someone who is in charge of millions of dollars of taxpayer money, her word should be inviolate. It's kind of analogous to what's going on with Anthony Weiner and tweetgate. Given his sorry track record of lying to the American public, Rep. Weiner (NY) should probably resign his post in Congress, and in my view, we should hold federally funded researchers to the same high standard of credibility.

Footnote: Erich Hall is still on death row.

Helen Mayberg: A case study in why we need greater transparency about conflicts of interest

A year ago, the Department of Health and Human Services proposed new rules governing the disclosure and handling of financial conflicts of interest by medical researchers who receive federal funding. The more stringent rules were prompted by Congressional findings that prominent NIH-funded researchers had failed to disclose significant consulting and other income, violating the agency's own regulations. The new rules would, among other things, require universities to post on a publicly available website information describing the specific financial conflict of interests of their federally funded researchers, according to Sheldon Krimsky, the Tufts University ethicist who wrote about the new rules in an article for Ethics in Biology, Engineering & Medicine last year.

Why is this so important? Because the current system of disclosure has proven woefully inadequate in providing consumers with information about financial conflicts that can skew medical research and adversely affect patient care. According to a 2008 Inspector General's report, the vast majority (93 percent) of institutions reporting conflicts of interest to the NIH did not describe the nature of their researchers' conflicts; in addition, 90 percent of the universities relied solely on the researchers' discretion in reporting conflicts, which is why there was so much failure to disclose in the first place.

Here's an interesting case in point. Dr. Helen Mayberg, a neurologist at Emory University School of Medicine, has testified in more than 50 death penalty cases, always for the prosecution in an attempt to discredit any mitigating evidence of brain damage in defendants on death row. Indeed, in a 2009 transcript (State of Connecticut vs Richard Roszkowski), Mayberg acknowledged that she has probably testified exclusively for the prosecution in more recent death penalty cases than any other doctor in the country, except perhaps Park Dietz, known by some as Dr. Death for his decades of testifying on behalf of the prosecution in high-profile cases.

While Emory officials say Mayberg has reported her expert witness work to them, they are under no obligation to disclose the full range of her extra-curricular activities to the public under existing federal rules. As a result, very few of Mayberg's colleagues or patients know of her extensive testimony in death penalty cases. And Mayberg goes to some lengths to keep her lucrative sideline out of the public eye.

For example, she had a friend (David Dobbs)* scrub her Wikipedia page of any reference to her death penalty work or her previous failures to disclose other conflicts of interest; here's a more comprehensive earlier version of her wikipedia page pre-scrubbing. I blogged here about Mayberg's collaboration with former psychiatry kingpin Charles Nemeroff and her previous failure to fully disclose conflicts of interest involving her work with deep brain stimulation, a controversial technique for treating depression.

Also missing from Wikipedia is the fact that she has so angered other neurologists with her death penalty testimony that they tried to get her drummed out of the American Neuropsychiatric Association. As one prominent neurologist says, it's not just that Mayberg always testifies for the prosecution in death penalty cases -- in effect, "trying to kill people" -- but that she goes to considerable lengths to rebut defense experts, often introducing inaccurate information and contradicting herself in the process.

"She uses a lot of maneuvers to say that [defense] findings in brain scans are not valid, yet at the same time, she's written articles saying the brain scans are valid," says the neurologist in the Washington, D.C. area who has written extensively about brain damage. "In fact, she uses the same brain scans that she says are invalid in the courtroom to diagnose depression in people whom she then treats with deep brain stimulation."

According to Krimsky, Mayberg's death penalty work is considered a significant financial conflict of interest under both the old and new NIH rules. And if the new rules are adopted, she would not only be forced to disclose the extent of her death penalty work but also the money she makes from it. According to lawyers who do for this kind of work, Mayberg makes as much as $500 an hour testifying for the prosecution in death penalty cases. And since she travels all over the country to testify, including to notorious death penalty states like Texas and Alabama, those hefty hourly fees add up.

In response to my query about how many death penalty cases Mayberg has disclosed since she came to Emory in 2004 and how much money she's made from this sideline, all Emory officials would tell me is that "she reported five instances of expert witness activity in 2009." You do the math.

*Correction: David Dobbs did not scrub Mayberg's wikipedia page; he merely added a link to a feature he had written about her for the New York Times magazine.

A lesson in how not to run for public office -- in Canada or anywhere else

In his latest blog, Paul Thacker, an investigator for the Project on Government Oversight (POGO) and former aide to Senator Charles Grassley, struggles to understand how Dr. Stan Kutcher, a psychiatrist turned politician in Canada, could possibly say that Paxil study 329, which Kutcher co-authored in 2001, hasn’t caused any particular controversy. Thacker was at a conference in Toronto the night of the Canadian federal elections, and the talk at dinner that evening was all about how Kutcher, who was running on the Liberal Party ticket, had threatened to sue a Halifax newspaper, The Coast, for writing an article about his involvement in study 329.

In his blog, Thacker goes over ground covered in Side Effects -- how flawed the 2001 Paxil study is, how it was ghost-written by a medical contractor for GlaxoSmithKline, the maker of Paxil, and then signed off on by its many authors, including Dr. Martin Keller, the principal investigator from Brown University, and Stan Kutcher. Thacker notes that Side Effects isn’t the only detailed account of ethically questionable behavior in study 329. The BBC also ran an investigative report on its flaws, and several medical researchers have called for a retraction of the study; see here and here.

Rather than own up to his involvement in what many consider a mockery of empirical research, Kutcher threatened to sue The Coast for libel, forcing it to issue a retraction and remove the offending article from its website (it was promptly archived by another site, Scribd). And then, as Thacker and other bloggers note, Kutcher and his henchmen went on the attack and essentially accused me of being a Scientologist.

For the record, I am not and have never been a Scientologist. The more pertinent question is: does Canada want politicians who engage in these kind of ad hominen attacks? Apparently not.

Paxil study author and psychiatrist turned politician loses Halifax election

Stan Kutcher, the psychiatrist turned politician who threatened to sue The Coast newspaper in Halifax unless it issued a retraction on a story it did about Kutcher's involvement with Paxil study 329 (see retracted story here) and my blog about it), lost yesterday's election, along with the rest of his Liberal Party. See story here.

Halifax newspaper buckles under to threat from psychiatrist turned politician

In recent years, experts (like Bill Kovach and Tom Rosenstiel) have warned that press freedoms are under increasing threat from economic pressures. As advertising and readers flee to the Web, they say, news outlets are more likely to cave in to pressure from corporate and political interests. Here's a disturbing example of this trend.

A few weeks ago, I was interviewed by a reporter for The Coast newspaper in Halifax, Nova Scotia. The reporter, Tim Bousquet, had discovered that the Liberal Party candidate in Halifax for the upcoming federal elections, Dr. Stan Kutcher, was one of the co-authors of Paxil study 329, a controversial clinical trial on the use of Paxil in treating depression in adolescent. When it was first published in 2001, study 329 purported to show that Paxil was safe and effective when in fact the actual data showed the opposite, as I reported in Side Effects and subsequent blogs. What New York prosecutors, several researchers and I found was that the study's authors manipulated and omitted data to make Paxil look safer and more effective in adolescents than it really was -- see background here. Given the study's serious flaws, researchers Jon Jureidini and Leemon McHenry recently called on the Journal of the American Academy of Child and Adolescent Psychiatry to retract the 2001 paper, according to the British Medical Journal.

Last Thursday, five days before the Halifax elections, which are being held May 2, Bousquet posted this article about Kutcher's involvement in study 329. Bousquet quoted me as saying that the researchers "essentially distorted the outcome measures." He also quoted Kutcher as saying that he stood by study 329 and didn't think it had caused any particular controversy. I thought the article was accurate except for two facts the reporter got wrong: he said that a secretary at Brown had leaked the information to me in 2003, when in fact the person who first blew the whistle on study 329 was the assistant research director in the department of psychiatry at Brown, and she first made me aware of some of study 329's flaws in 1996. As I explain in Side Effects, I was unable to pin down those particular allegations until 2004, when the New York State Attorney General's office sued GlaxoSmithKline for defrauding consumers by not telling them or doctors the full story about Paxil. In their lawsuit, the New York prosecutors found numerous flaws in the study 329, including the fact that the researchers had changed the primary outcome measures for the trial without disclosing that fact in the published paper. They also found that GlaxoSmithKline knew that the study 329's results were negative -- i.e. -- that the clinical trial didn't find Paxil more effective than placebo in treating depression -- but according to an internal memo, company officials decided to publish the study as a positive result anyway and indeed had it ghost-written by a medical contractor and then signed off on by all the co-authors, including Kutcher.

Kutcher's lawyers immediate responded to Bousquet's April 28 article by threatening to sue the newspaper for libel unless it immediately issued a retraction. Even though Bousquet backed up his article's assertions with documentation, the Coast decided to issue an apology and retraction anyway; see here. And then the newspaper simply removed the original article from its website; see here. So now readers of The Coast can see the apology but not why it was issued in the first place. Fortunately, a website called Scribd saved Bousquet's original piece along with a follow-up article about Kutcher's threat to sue The Coast if it didn't retract the piece.

As you can see from Scribd's follow-up piece, a blog here, and some comments on the original article (all of which were removed), Kutcher's hatchetmen are trying to paint me as a Scientologist in an effort to discredit me and the original story. That's a tactic as old as dirt; as a mental health reporter for The Boston Globe in the '80s and '90s, I remember when the drug industry and the psychiatrists on its payroll used that ridiculous canard to attack anyone who questioned their wonder drugs; indeed, in Side Effects, I write about how Eli Lilly, among others, attacked Dr. Martin Teicher, a respected psychiatric researcher at McLean Hospital, as a Scientologist when he first raised questions about the safety of Prozac in the early '90s.

All of this makes me wonder: where have The Coast and its editors been all these years? And do they really want to go down in history as an example of the not-so-free press buckling under to craven threats?

Serious flaws and conflicts skewed results of largest antidepressant study ever done

In 2006, researchers first published results from a $35 million NIMH-funded study of antidepressants known as STAR*D, claiming it proved the effectiveness of second-generation antidepressants used alone and in combination with each other. The NIMH chimed in with press releases extolling "new strategies" that help depressed patients become symptom-free, and the findings became the basis for American Psychiatric Association's guidelines calling for the open-ended use of antidepressants in treating depression.

But, as Edward Pigott, a Maryland psychologist, reveals in several published papers and his blog, it was all a big lie. Pigott shows how the STAR*D authors, 10 of whom had financial ties to antidepressant makers, played unethical games with the data to make all of the antidepressants in the study look far more effective than they really were. For instance:
       *The researchers changed the primary outcome measure from the Hamilton rating scale of depression (considered a gold standard in measuring depression) to a proprietary rating scale owned by the principal investigator, Dr. John Rush, a psychiatrist at the University of Texas (who by the way was investigated by Senator Grassley for failing to disclose extensive conflicts of interest). And they made the change even though the secondary rating scale had been used in clinical treatment, thus tainting it as an objective research measure. Furthermore, in the published results, Rush and his co-authors didn't bother to disclose this change (which skewed the results in favor of the drugs).
       * They failed to count patients who had dropped out as treatment failures, thus further skewing results in favor of the drugs.
       * Halfway through the study, they included patients with only mild depressive symptoms who had originally been excluded because they didn't meet the original criteria for being depressed, again making the results look better than they were.
       * They repeatedly rounded up percentages to make it look as if the antidepressants in the study were more effective than they really were. Yet they didn't round up any findings showing the percentage of negative side effects among patients taking these drugs.

After re-analyzing the data from STAR*D, Pigott found that in contrast to STAR*D’s published findings, only 108 of its 4,041 patients (2.7 percent) went into remission in the acute phase of the study. And of those initial patients, only 38 percent obtained remission after being dosed with other medications in three later phases of the trial. In every phase, more patients dropped out than were remitted, and this drop-out rate increased throughout the study. As Pigott says in a paper published this month in the journal Ethical Human Psychology and Psychiatry, "this reality directly counters the study's false claim that about 70 percent of those who did not withdraw from the study became symptom-free."

Three years later, in a review article for the Journal of Clinical Investigation, Dr. Thomas Insel, director of the NIMH in 2006 and today, pretty much acknowledged the inadequacy of second-generation antidepressants in treating depression. To quote Insel:

In 2007, the third and fourth most heavily purchased medications in the United States were antipsychotics and antidepressants, respectively, with a combined market of $25 billion. Remarkably, despite the heavy use of these medications, we have no evidence that the morbidity or mortality of mental disorders has dropped substantially in the past decades.

Instead, as Pigott points out in his most recent paper, "the morbidity and chronicity of mental disorders appears to be increasing with a twofold to threefold increase between 1987 and 2007 in the number of Americans receiving disability payments for such disorders." Robert Whitaker, of course, argues in his new book, Anatomy of an Epidemic, that it is the very overuse of so many psychoactive drugs with severe side effects that has led to this exponential increase in the number of Americans disabled by mental illness.

Whether or not you buy Whitaker's hypothesis -- and it certainly warrants further investigation -- the fact is that the STAR*D study, like Paxil study 329 was flawed in so many ways that its published results should be retracted.
Not only did most of the STAR*D authors including John Rush have financial ties to Forest Labs, the maker of Celexa, and other antidepressant makers who stood to benefit from the study's positive findings. But as Pigott reveals, the very same NIMH officials who were tasked with the oversight of this $35 million multi-center study were also allowed to put their names on STAR*D studies published in the New England Journal of Medicine and the American Journal of Psychiatry, an egregious conflict of interest that should never have been allowed.

Interestingly, while Insel acknowledges the inadequacy of current antidepressants in his 2009 review, there is nothing on NIMH's website that points to this more sober assessment, despite the existence of five meta-analyses that show "modest to no" advantage of antidepressants over placebo in clinical trials. Pigott concludes that it is hard to find any reason for this pro-drug bias "other than convention, ease to prescribe for physicians, and the success of pharmaceutical companies' relentless marketing efforts."

Let's fix the perverse financial incentives in Medicaid before hacking its budget

Medicaid and Medicare are in the news of late, as Congressional Republicans spar with President Obama and the Democrats on how best to rein in the ballooning costs of these entitlement programs, which make up a growing share of federal and state budgets. But what few policy makers seem to be talking about -- at least in public -- are the perverse financial incentives built into the system that allow the companies who manage Medicaid contracts on a statewide basis to make profits at the expense of quality health care for Medicaid recipients. As a result of these perverse incentives, many Medicaid patients, particularly those being treated for mental health problems, are either terribly under-served or in some cases, badly over-treated. The upshot, in many cases, is poorer health outcomes and higher Medicaid costs.

Allow me to explain. In most states, Medicaid contracts for mental health and substance abuse are separated out from medical services and handled by managed care companies that make their money from keeping patients out of expensive hospitals. As a result of the way many contracts have been drawn up, drug treatments for emotional and behavioral problems do not count as costs to the behavioral health managed care entity, but instead fall under the plan's general prescription drug coverage. However, hospitalizations and psychosocial treatments (such as different forms of therapy and family interventions) do fall under the managed care's costs. So to make a profit, managed care in almost every state has done a spectacular job over the last two decades of limiting hospitalizations and access to psychosocial interventions, according to a new Hastings Center Special Report, which focuses primarily on troubled children.

As the report concludes, it's much easier for "patients to obtain referrals for medication management and psychopharmacology." This perverse incentive goes a long way to explaining why so many Medicaid recipients, both children and adults, are prescribed expensive psychotropic drugs, which cause serious side effects, rather than alternative therapies, which might be more effective and less hazardous to their health. Managed care companies make more money that way.

As one top medical official for New York State told me, "If you're a managed care entity and the pharmacy benefit is not part of your budget, you're happy if a symptom can be controlled by someone prescribing a dubious and expensive drug. It's not your problem." Or, as the authors of the Hastings report put it,

"The country's mental health care system makes it difficult for children to access psychosocial care, but relatively straightforward to access medication treatments (even if those treatments are not monitored or reassessed as recommended)."

And the same, of course, holds true for adults.

Not only do individuals with mental health problems suffer as a result, but state governments actually end up spending more when these patients don't receive the most effective treatments and interventions. Some patients will inevitably "end up on the streets or in prison where the costs don't accrue to the managed care companies," the New York state medical official explains. The states, of course, still pick up the costs -- but out of separate budgets for prisons, homeless shelters and programs for troubled teens.

The plot thickens. In many states, large insurance companies such as United Health care, WellPoint and Blue Cross Blue Shield have joined large managed care companies such as Americhoice and Centene in managing Medicaid contracts, according to this article in The Washington Post. Some states have flat-rate contracts with managed care companies that are designed to balance the need to limit costs with providing appropriate mental and physical health care. But in other states such as Colorado, Florida and Tennessee, managed care companies have what is known as "at-risk contracts" -- contracts whereby they make a percentage profit based on how much is spent on each Medicaid patient. And with such contracts comes another perverse financial incentive that, in some cases, make patients sicker.

For example, some managed care companies actually benefit twice-over when patients are over-prescribed anti-psychotic drugs such as Seroquel and Zyprexa, according to Edward Knight, a former executive with a managed care company in Colorado and a recovery consultant. This is how: while the behavioral health arm of the company makes money by referring patients for drug prescriptions rather than more expensive psychosocial treatments, another arm of the company makes money by managing the diseases such as obesity and diabetes caused by the over-use of these drugs. The off-label use of anti-psychotics like Seroquel, Risperdal and Zyprexa is widespread in many states, with disastrous effects on some patients, as many bloggers, myself included, have already noted. To think that some companies managing Medicaid contracts are actually profiting from that over-use is indeed perverse.

Seems to me that until we do something about the conflicting financial incentives that are built into the Medicaid system, fighting over how to cut Medicaid funding to the states is a waste of time. As the New York medical official says, setting up contracts based on a specific dollar amount is fruitless. "If it's just dollars, [the managed care company] will cheat and figure out ways to get other entities to pick up costs, or they'll just deny care," he says. "We have to change the contract incentives so that these companies can earn X number of dollars when they improve health care. We have to get to risk-based contracts based on performance metrics rather than profits." Amen.