Photo Credit: Beacon Press
September 10, 2013
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The following is an excerpt from Enrico Gnualati's new book
Back to Normal: The Overlooked, Ordinary Explanations for Kid’s ADHD, Bipolar, and Autistic-Like Behavior (Beacon Press, 2013):
On December 13, 2006, paramedics arrived at the Plymouth County, Massachusetts, home of four-year-old Rebecca Riley only to find her slumped over on her parents’ bed, dead. The medical examiner on hand identified the cause of death as heart and lung failure brought about by the medications she was on. Rebecca was being prescribed Depakote, Seroquel, and Clonidine by Dr. Kayoko Kifuji, a Tufts–New England Medical Center child psychiatrist. She had diagnosed Rebecca with ADHD and bipolar disorder when she was two years old. Rebecca’s death provoked a national debate on how a child as young as two could ever be diagnosed with major mental illnesses and be put on powerful tranquilizers. Katie Couric eventually covered the story in a CBS 60 Minutes segment.
Ultimately, Rebecca’s parents were tried for and convicted of murder due to allegedly overdosing her. But this harrowing outcome didn’t take the national spotlight off the shocking revelation that a toddler could be diagnosed with mental illness and put on not just one but three powerful tranquilizers. None of the drugs Rebecca was prescribed was approved by the Food and Drug Administration for use with kids her age—not then and not now. There was absolutely no robust scientific justification for Dr. Kifuji making the medication choices that she made. How could a reputable psychiatrist be so inclined to diagnose a child so young with diagnoses so severe and treat with medications so unapproved? The main answer lies with the spectacular success of twenty-first-century pharmaceutical marketing of psychiatric drugs.
In 2008, psychiatric drugs sold in the United States netted their makers $40.3 billion. A good portion of that amount involved drugs commonly prescribed to kids. A Wall Street Journal report indicates that between 2002 and 2007, prescriptions for psychiatric drugs for kids rose by nearly 45 percent. The most recent estimates suggest that up to eight million American kids are on one or more psychiatric medications. Meds for kids are big business and highly profitable.
Prices of ADHD meds at the middle dose for ninety pills on Drugstore.com in 2011 were Concerta, $540; Vyvanse, $532; Intuniv, $500; Adderall, $278; and Ritalin, $191. The price of the most common antidepressants, like Prozac, Celexa, Lexapro, Zoloft, Cymbalta, and Wellbutrin, for ninety pills, was around $380. Two of the drugs prescribed to Rebecca Riley by Dr. Kifuji happen to be quite pricey. Drugstore.com rates in 2011 for 180 500 mg tablets of Seroquel were $1,048 and for Depakote, $708.
Among drug reps, it is common knowledge that kids are a lucrative market. At the urging of doctors, parents, and teachers, kids are required to buck up and take their meds. In the words of Gwen Olsen, who worked for fifteen years as a drug rep with such pharmaceuticalindustry mainstays as Johnson & Johnson and Bristol-Myers Squibb: “Children are known to be compliant patients and that makes them a highly desirable market for drugs, especially when it pertains to largeprofit-margin psychiatric drugs, which can be wrought with noncompliance because of their horrendous side-effect profiles.” Most large-profit-margin psychiatric drugs are approved by the FDA strictly for use with adults, not kids. However, doctors are allowed to use their discretion and prescribe them to kids for “offlabel” purposes. Doctors can use their medical instincts to determine whether a drug approved for adults might also ease the suffering of kids. But there is no scientific backing for such use. The studies haven’t been conducted. The FDA approval hasn’t been obtained. Off-label prescribing relies on doctors’ instincts alone. While drug manufacturers and their marketing staff are bound by law not to influence doctors’ off-label prescribing habits, it’s not the law that’s foremost on the
minds of drug reps fanning out to doctors’ offices all over the country.
It’s upping sales. The right to use adult meds with kids for off-label purposes has left many physicians easy prey to drug reps and pharmaceutical companies’ marketing ploys. A glaring example of this was uncovered in the largest health-care fraud case ever handled by the US Department of Justice, in 2009. Pfizer agreed to a $2.3 billion settlement for promoting off-label use of a variety of drugs, one of which was the antipsychotic medication Geodon. One of Pfizer’s illegal actions was paying 250 child psychiatrists to promote its off-label use with teens. Dr. Neil Kaye, for example, was paid $4,000 a day in speaker’s fees to give speeches to other physicians with titles like, “the off-label use of Geodon in Adolescents.” Geodon happens to be a highly expensive and highly profitable drug. At Drugstore.com in 2011, it cost $1,400 for 180 40 mg capsules. It currently nets Pfizer $1 billion a year.
At the time of Rebecca Riley’s death in 2006, the number of drug reps in the United States was at an all-time high: 102,000. It was the heyday of doctor-seducing, trinket-driven psychiatric medicine. Carl Elliott, in his shrewd article in the Atlantic that year, titled “The Drug Pushers,” spoke of drug reps ponying up sports tickets for doctors, televisions for their waiting rooms, and expensive tropical vacations. One drug rep revealed to Elliott that he constructed a makeshift putting green in a hospital and gave away a putter to any doctor who got a hole in one.
Of course, doctors deny that their diagnostic decisions and medication-prescribing practices are swayed by drug reps’ sales pitches, promises of lunches and gifts, or provision of free samples of the medications the drug rep is promoting. But the research doesn’t back them up. Many doctors who take free samples of drugs are far more likely to later prescribe that drug, even when cheaper and equally effective drugs are on the market. One study that pored over psychiatry residents’ chart notes found a high correlation between drug reps’ sales visits and new prescribing habits involving the drug promoted. The turnaround time in switching over to prescribing the freshly promoted medication was fast—within twelve weeks. An often-cited 2001 survey shows that 61 percent of doctors believe interactions with a drug rep have no influence on their medical decisions. Yet only 16 percent of them believe this is true of other doctors.
A surprisingly high number of doctors actually rely on information drug reps provide to keep up with what is supposedly cutting-edge in the world of pharmaceuticals. Several years ago, a Kaiser Foundation poll of 2,608 doctors indicated that 75 percent of them found the information supplied by drug reps “very useful” or “somewhat useful.”
More often than we’d like to think, drug reps are quasi-medical advisors. It’s somehow overlooked that they’re selling a product and that the information they provide to doctors detailing how their new medication might help certain patients with certain emotional problems, better than the alternatives on the market, is potentially biased. After all, they’re trying to make a sale. The conflict of interest inherent in drug reps supposedly providing objective information about the uses and effectiveness of medications, yet upping the sales of their own, mirrors what exists in the entire field of psychiatric-medication research. Take the case of Dr. Joseph Biederman. He has the honor of being chief of the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD at the Massachusetts General Hospital, the teaching hospital of Harvard University. Dr. Biederman’s work is responsible for loosening our understanding of how manic-like behavior should be thought of in kids.
Historically, manic behavior has been considered rare, especially in kids. When psychologists like me see it in a person, it can be identified right away. The manic person hasn’t slept for days, believes he or she has inexhaustible energy and superhuman abilities, and, most prominently of all, talks a blue streak. Dr. Biederman redefined manic behavior in kids in terms of irritability, severe tantrums, and rapid mood swings. His work burst the doors wide open. This looser definition of manic like behavior heralded a fortyfold increase in the diagnosis of bipolar disorder in youngsters, based on the latest data set we have.
In a Senate hearing in 2008, it was revealed that Dr. Biederman had received $1.6 million in speaking and consulting fees from many of the pharmaceutical-industry giants manufacturing antipsychotic medications for use with children thought to have bipolar disorder. It turns out that Dr. Biederman was on the payroll at AstraZeneca, the makers of Seroquel, which is among the most frequently prescribed drugs for bipolar disorder with kids today and one of the medications prescribed by Dr. Kifuji to Rebecca Riley back in 2006.
Dr. Biederman’s case is just one example of the industry norm. Large pharmaceutical companies commonly fund psychiatric-research programs. Because of this, there is an inherent potential for biased reporting or for researchers to strictly report favorable findings on the medications they are funded to study. Results that are successful get published and end up on glossy brochures in doctors’ offices. Results that are unsuccessful don’t get published and are filed away in the basement. The Medical Products Agency in Sweden estimates that as many as 40 percent of clinical studies of antidepressants don’t get published or publicized. Before approving a drug, the FDA does, however, require a pharmaceutical company to release the results from all the studies it paid to be conducted, whether a drug’s outcome proved to be successful or not. But to get at that information, sometimes bold action is required, such as making use of the US Freedom of Information Act to petition the FDA to obtain the full story on clinical drug trials—the ones that show the medication was effective, as well as the ones that show it is a dud.
This is exactly what Irving Kirsch did and reported on in his compelling book, The Emperor’s New Drugs: Exploding the Antidepressant Myth. Dr. Kirsch and his staff accessed the FDA data available on a host of popular antidepressants and ran the numbers. Across thirtyeight clinical trials involving three thousand patients, the benefit of being on an antidepressant was only slightly better than being on a placebo. He sums up the results in his book with the following startling fact:
“Improvement in patients who had been given a placebo was about 75% of the response to the real medication.” Placebo-type studies are generally considered to be the most scientifically trustworthy ones. Two identical groups of depressed people might be divided up. One group is given the real pill, which is the medication that is being tested. The other group is given a placebo—a fake pill that is made to look like the real pill but has none of the psychoactive ingredients of the real pill.
After a while, all participants involved may be interviewed by a research assistant on how much their depression has improved. The research assistant is unaware of who is taking the real pill or the fake pill. That is what makes a study a double-blind, placebo-controlled one. The research assistant is blind to who is taking what so that he or she does not arrive at a biased viewpoint. Dr. Kirsch’s discovery on the minimally higher effectiveness of antidepressants over placebos is actually not so controversial. Back in January 2003, when Prozac was approved by the FDA for use with children, the decision was based mainly on three studies. One study showed an unsuccessful outcome: depressed adolescents were as likely to get better taking a placebo, as they were taking Prozac. The response rates were extraordinarily high—65 percent. That means 65 percent of the adolescents became less depressed whether they were given Prozac or a sugar pill. The two other studies did indicate that depression in children and adolescents improved with Prozac, over placebos. In one, 56 percent of the respondents got better on Prozac, versus 33 percent on placebos. On the other, 41 percent of respondents got better on Prozac, as compared with 20 percent on placebos.
Doctors are often unaware of the amazingly high improvement rates using just placebos. Patients can get better taking a sugar pill placebo, even when they are explicitly told that there is no medicinal ingredient in it to treat their ailment. This was the finding of Harvard Medical School professor Ted Kaptchuk and his fellow scientists in a recent study with patients complaining of irritable bowel syndrome. He divided eighty patients into two groups. One got no pill. Members of the other group were told to take two pills a day that were openly described as “like sugar pills,” with no medicinal ingredient in them. The bottles that contained the pills they were to consume had the word “placebo” clearly printed on the front. A stunning 59 percent of those taking the pills reported relief from taking them. For many people, the simple act of taking a pill, whether or not they know it has little medicinal value, can lead to improvement—particularly if the medical and psychiatric conditions for which they are taking it are vague or loosely defined.
What about Seroquel, the blockbuster antipsychotic drug that sells for over $1,000 for 180 500 mg tablets on Drugstore.com and has generated upwards of $17 billion in sales since 2004?35 This was one of the medications Rebecca Riley was prescribed for bipolar disorder. How does it measure up against a placebo? Based on a pair of studies in the prestigious American Journal of Psychiatry and the Journal of Clinical Psychopharmacology, the response rate is close to 55 percent for Seroquel, as opposed to 37 percent for placebos. This hardly inspires confidence.
It’s like saying Seroquel helps 19 percent of the patients who take it, the rest of whom would have gotten better by simply taking a sugar pill. Moreover, sugar pills, unless taken in mass quantities, don’t produce weight gain, but Seroquel does. Antipsychotics like Seroquel have been associated with an average weight gain of twelve pounds a year. The New York Times in 2010 reported that in civil lawsuits brought against AstraZeneca, this drug manufacturer knowingly hid the Seroquel–weight-gain link and instead published a study suggesting that the drug was linked with weight loss!
Excerpted from Back to Normal: The Overlooked, Ordinary Explanations for Kid’s ADHD, Bipolar, and Autistic-Like Behavior by Enrico Gnaulati, PHD (Beacon Press, 2013). Reprinted with permission from Beacon Press.