Mental Health Inc

by Art Levine

  The VA Inspector General’s office not only wouldn’t permit me to interview the consultant Shepard, claiming patient confidentiality, but declined to reveal what medical guidelines or scientific research the VA reviewed before releasing its report. The same blanket claim of confidentiality applied to the VA offering any scientific justification for VA doctors plying Andrew White with levels of Seroquel that were as much as 50 percent higher than that maximum recommended dosage of 800 mg for schizophrenics. Even when I presented her with a confidentiality waiver from Andrew White’s parents, the IG’s counsel, Regan, wouldn’t answer questions about the VA’s care of Andrew White or even acknowledge that the report reviewed the treatment of Andrew White and Eric Layne, who are listed only as Patient A and Patient B. “We don’t discuss the cases of individuals who are the subject of our investigations,” she said. End of story.

  But it didn’t prove to be the end of the story for Stan White and other families seeking answers—and changes in military and VA treatment practices. And the VA’s conclusions, no matter how shoddily prepared, had lasting consequences. It meant, in practical terms, that the surviving family members of Layne, White and most of the few hundred other young soldiers and veterans who have died after taking Seroquel had few grounds for filing a lawsuit against the government. And it helped pave the way for thousands of more soldiers and veterans to be exposed to Seroquel as a sleep aid on the battlefield or as a treatment for PTSD after coming home. “I don’t know what standards the VA was meeting if Andrew got such high dosages of Seroquel,” Stan White points out. He and Shirley believed, in the end, that the IG report didn’t really answer the questions about the deaths of their son and Eric Layne.

  Regardless of its shortcomings, members of Congress accepted the Inspector General’s conclusions discounting the dangerous prescribing that helped kill White and Layne. That, in turn, undermined any initiatives to hold the VA accountable for its practices, or any further probe of these soldiers’ deaths and the overprescribing of antipsychotics to veterans in general. One aide to then-Senator Jay Rockefeller, the legislator who asked for the Inspector General investigation, insisted to me, “The VA took this very seriously. The VA faces a major challenge with suicides and PTSD, but it has done a lot of efforts to improve mental health care for veterans.” The staffer added, citing the mixture of prescriptions with alcohol, “I’m sure the VA physicians tell their patients not to drink, and this important advice is ignored.” But this blame-the-victim perspective common in Washington doesn’t reflect the absence of alcohol in the toxicology findings for Layne and White—or the reality that, in too many of the deaths of soldiers such as Cpl. Nicholas Endicott, they were just following the doctor’s orders.

  Stan White, dressed in his best dark blue business suit and armed with a folder thick with letters from grieving relatives, urgently sought to convey the need to protect our soldiers and veterans from deadly, substandard care when he went with his wife to the offices of each member of the House and Senate veterans committees for the first time in April 2009. He visited about forty in all.

  Reading those letters now is like walking through a graveyard of despair and naive hopes for a meaningful response, distress signals from the not-so-distant past that went unheeded. “These are our heroes we are mistreating,” Derek’s grandmother pleaded. With rare exceptions, White only got to meet with the congressional aides who listened with polite concern as he made his case.

  “I’m Stan White from Charleston, West Virginia,” he told them. “I’ve lost two sons in the military. One was killed in battle. One died from medication for PTSD. Through my research, I’ve found numerous others: I think that’s a problem. I want someone to investigate it. Here is my evidence, here are my charts.” He then gave them his carefully prepared folder of research, news clippings and letters. During that first visit to Washington, he presented a list of over fifty suspicious deaths gleaned from news accounts and public records found by White and his allies. By 2016, the list would grow to over four hundred soldiers and veterans.

  In a plea that now seems at once so sensible and heartfelt, the cover letter with his packet declared, “We believe that the DOD and VA need to provide more counseling and therapy for our veterans. Most important is the need for research as to why the combination of these medications seems to lead to so many deaths.”

  Citing a recent wave of salmonella-poisoned food, he said at the time, “When six people die from contaminated peanut butter, the factory is shut down and there’s a massive recall. But when we find at least fifty-one military men have died in their sleep, no alarm seems to sound.” He, for one, would keep trying to sound the alarm, but what he discovered about the influence of the drug industry in Washington would truly shock him.

  CHAPTER 7

  Mr. White Comes to Washington: FDA Showdown over Seroquel

  THERE WAS LITTLE SIGN THAT ANYONE IN CONGRESS OR THE VA WAS really listening to Stan and Shirley White. Still, they and other West Virginia families, joined by a handful of medical experts and reformers concerned about Seroquel’s effects, attempted to convince the FDA to at least not expand the drug’s use.

  During their visit to Washington in April 2009, the Whites attended a hearing in which the influential FDA Psychopharmacologic Drugs Advisory Committee was considering a request from AstraZeneca. The company wanted to considerably expand Seroquel and its extended-release version, Seroquel XR, beyond its approved use for schizophrenia and bipolar disorder. The suburban Hilton ballroom was packed with nearly three hundred people, mostly AstraZeneca and other well-tailored drug industry officials and doctors. The handful of voting members of the committee listened to the largely pro-industry FDA experts and polished AstraZeneca scientists make their case for broadening the drug’s use to cover anxiety and major depression.

  The Whites, overwhelmed by it all, were pointed to assigned seats and waited with some other aggrieved victims and critics of the drug, including Janette Layne, for their allotted three minutes near the end of the meeting to offer their appeals. The final decision would be made by the full agency. Despite the FDA’s (loosely enforced) conflict-of-interest rules, these advisory panels tend to support the goals of drug companies and their findings are generally approved by the FDA.

  In fact, less than a week before the April 2009 hearing the Whites attended, the Philadelphia Inquirer reported that Dr. Jorge Armenteros, the chair of the committee was, in fact, a longtime paid speaker for AstraZeneca who had promoted Seroquel and also sought to drum up more AstraZeneca cash by proposing new research on Seroquel. Armenteros held this chairman post for five years without any challenge until the newspaper contacted the FDA for comment shortly before publication. Suddenly, the FDA determined that Armenteros and four other drug-industry subsidized researchers sitting on the committee shouldn’t be allowed to vote on AstraZeneca products, and were hastily replaced by temporary members, some also with past ties to the drug industry.

  These revelations emerged from documents that were uncovered during lawsuits filed on behalf of thousands of plaintiffs who developed diabetes while on the drug. Armenteros, who had published research on the value of antipsychotics for such off-label uses as ADHD, wasn’t available for comment. Philadelphia attorney Steve Sheller told the Inquirer, “The industry is infected with greed. You can’t trust the approvals, you can’t trust the studies, and now you can’t trust the FDA.”

  By the time the FDA advisory committee met in the spring of 2009 to discuss the company’s request for approval to market the drug to millions of potential new patients with depression and anxiety, AstraZeneca’s Seroquel research and safety claims were essentially thoroughly discredited—except, it seemed, in the eyes of the FDA.

  A year later, the company would be forced to pay a half-billion dollars to the Department of Justice and twenty state Medicaid programs for hiding Seroquel’s dangers in its alleged illegal marketing campaign. Even in the months leading up to this FDA hearing, the company’s skewed resear
ch on Seroquel was becoming a major scientific scandal. For instance, as a result of still more findings from the 19,000 pending liability lawsuits against AstraZeneca, released internal documents showed that AstraZeneca buried studies showing harmful effects back in the 1990s, when the FDA first approved Seroquel for schizophrenia. As The Washington Post reported, in a damning August 1997 email regarding the never-published “Study 15” that showed 45 percent of patients had significant weight gain, AstraZeneca executive Richard Lawrence praised company physician Lisa Avantis for putting a “positive spin” on this “cursed study” by masking the weight gain: “Lisa has done a great ‘smoke and mirrors’ job.”

  Just as disturbing, The New England Journal of Medicine reported in January 2009 that patients receiving the atypical, new generation antipsychotics, including Seroquel, faced a risk of sudden cardiac death that was over 200 percent higher than those who weren’t using the medications—even higher than the better-known risk posed by the older generation of antipsychotics. The lead author, Dr. Wayne Ray of Vanderbilt University, told The New York Times, “The implication of this study is that physicians need to do a very careful cardiovascular evaluation prior to prescribing these drugs”—while using the lowest possible dosages if treatment moves forward. Years later, those practices still haven’t been adopted by the Department of Veterans Affairs.

  Ray attended the April 2009 hearing and the committee granted him permission to give a presentation that warned about expanding the drug’s approved uses. But before he could make his case, the committee was briefed by that wily ally of the pharmaceutical companies, the FDA’s Dr. Thomas Laughren, who by June of 2009 would also help make the case that Seroquel was safe for kids.

  Now, as Laughren and other FDA officials prepared to spin the findings on Seroquel before this advisory committee, it was especially relevant that he had in 2004 reportedly misled another FDA advisory committee about the safety risks arising from the expanded use of antidepressants for kids.

  So in April 2009, Laughren had a new chance to shape the findings on another drug, Seroquel, and help advance the pharmaceutical industry’s agenda yet again. Yet with the scathing publicity over rigged Seroquel studies, along with the spotlight on FDA employees and advisors who were seemingly colluding with the drug industry, this advisory committee had good reason to appear a bit more cautious while deciding if it would give AstraZeneca everything it wanted.

  What AstraZeneca sought was a way to make more money by winning FDA approval for first-line “monotherapy” treatment with its newer extended-release drug, Seroquel XR, for depression and anxiety. An added bonus for the company: Seroquel XR’s exclusive patent wouldn’t expire until 2017, roughly five years after regular Seroquel’s patent expired, opening up the competition to generics. A second preference, but still enormously lucrative, would allow the drug to be used as an “adjunct” therapy if other FDA-approved drugs weren’t fully successful; the potentially deadly Seroquel could be, with the FDA’s blessing, used to “augment” the effects of other medications. All of this would expand Seroquel’s potential market from less than 4 percent of the adult population with schizophrenia and bipolar disorder to nearly 10 percent of adults with generalized, unrelenting anxiety disorder, or those with major depression. (That latter diagnosis was defined by a seriously disruptive bout of depression lasting more than two weeks in the previous year.)

  The increased sales opportunities could potentially add over fourteen million new FDA-approved patients, not counting millions of more off-label customers eager for stress relief. With the added appeal of Seroquel’s heavy sedation, the FDA’s full-throated approval of the drug for anxiety and depression could ensure that its future earnings would dwarf the nearly $5 billion a year it was on track to earn in 2009. The retail cost of Seroquel XR was then over $12,000 per patient a year for just two pills a day.

  Perhaps chastened by all the recent scandals, and facing an impossible-to-ignore New England Journal of Medicine study on cardiac risk, Laughren was essentially forced to acknowledge the potential safety risks of the drug. Yet he still accepted at face value the array of AstraZeneca’s subsidized research on Seroquel’s effectiveness for anxiety and depression. While telling the panel the drug was safe enough for its current uses, he cited possible metabolic and diabetes risks; the tremor-filled neurological disorder tardive dyskinesia; and the new findings of sudden cardiac death associated with atypical antipsychotics.

  Before the committee could make its decision, or critics could raise concerns, a series of smooth AstraZeneca scientists made their case. This new set of company experts—replacing the earlier researchers disgraced by their exposed emails—blithely continued the same sales job on the drug’s safety and effectiveness, all buttressed with impressive-seeming PowerPoint slides. The only adverse effects to worry about for some patients were such modest side effects as dry mouth and dizziness, they reassured the panel. The drug certainly couldn’t kill you, they argued. Yet the company’s own data showed that nearly seven times as many people who used the medication died during drug trials compared to those on placebo, but since far fewer people received placebos, the rate of death was about the same, they contended. (By April 2005, though, the FDA had already warned that all antipsychotics had a 170 percent higher risk of death for dementia patients than placebos.)

  Stan White’s speaker number was soon called, and when he stood before the panelists, he was, like all the other members of the public, only allotted three minutes to funnel all his frustration and pain into testimony that might sway them. After explaining how his son died from a combination of drugs that included Seroquel and that nearly ninety other veterans and soldiers had died up to that point while taking the drug, he said, “My belief is that overuse of these medications has caused our soldiers and Marines to die.”

  His wife Shirley emphasized in her brief talk the betrayal she felt. “He was told, and I as his mother was told, ‘These medications will not harm you,’” she said. “I trusted the doctors to do what was best for my son, and he died in his sleep.”

  There was little sign that the panelists were paying much attention as the families spoke. In the end, the advisory committee didn’t accept Seroquel as a first-line drug for depression and anxiety, but approved its use as an adjunct treatment for depression. This paved the way for AstraZeneca to legally enter a new market potentially as lucrative as the one dominated by Abilify.

  • • •

  PART OF THE VA’S ONGOING RELUCTANCE TO SERIOUSLY REIN IN THE HIGH-RISK, off-label prescribing of antipsychotics stems from the influence of the drug industry on both the agency’s top researchers and its local doctors charged with caring for troubled veterans. That’s a pattern, of course, affecting virtually all of mental health care. For instance, some of the earliest work that pushed Seroquel on veterans came from Dr. Mark Hamner, the director of psychopharmacology research and PTSD clinical care at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. With the support of AstraZeneca, he coauthored a series of papers boosting Seroquel and launched additional research on the drug. The results were apparently so unimpressive that most were never published in a medical journal. With AstraZeneca funding, he reported in February 2003 an uncontrolled—or “open label”—study in the Journal of Clinical Psychopharmacology that found in a short trial of Seroquel that it produced “significant reductions in core PTSD symptoms” and only mild, “transient” adverse events. Even while lawsuits were revealing damning evidence against the drug, Hamner remained on the bandwagon for the drug.

  When I first spoke to Hamner in 2011, he denied that the funding he had received from AstraZeneca over the years—which he declined to reveal and wasn’t required to be disclosed publicly at the time—had any impact on his research or talks about the drug. “I don’t think it does at this point,” he said.

  In 2004, Hamner appeared on an AstraZeneca-funded panel at the American Psychiatric Association talking about broadening the use of atypical a
ntipsychotics beyond then FDA-approved uses. He cited preliminary studies showing positive benefits with Seroquel and other antipsychotics, especially Risperdal, as an adjunct treatment for PTSD. Although he mentioned the possible metabolic risks, he said of his own studies on Seroquel at relatively lower doses, “From a safety standpoint we did not see changes in weight … or significant changes in vital signs.”

  AstraZeneca was apparently pleased with Hamner’s work in this field because it funded directly or served as a “collaborator” with the VA on two additional twelve-week studies that he conducted measuring Seroquel’s impact on PTSD symptoms when compared with a placebo. Neither study was published in a medical journal until some of the underlying data finally made it into print in 2016, and for nearly a decade or more the studies’ outcomes were known only to Hamner and presumably AstraZeneca. For years, the results weren’t even listed on the federal government’s voluntary clinicaltrials.gov website.

  AstraZeneca and its allied researchers were just following the common industry practice of hiding as many side effects and poor outcomes with their drugs as possible. The results of roughly half of all clinical trials are never published anywhere, often to mask disappointing or alarming results about a drug or procedure; that has prompted a worldwide campaign of over six hundred medical organizations and journals, led by Alltrials.net founded by The Guardian columnist Dr. Ben Goldacre, to force the registration of all trials and the disclosure of all results. But Hamner told me in 2011 that he was in the process of readying both studies comparing Seroquel to a placebo for publication. When asked why he hadn’t published the results of his VA-based research, he insisted, “There is no pressure or anything like that from AstraZeneca not to publish. Certainly we are being very careful about the analysis.”