Anatomy of an Epidemic (34 page)

After that initial fourteen-month period of treatment, the investigators followed up periodically with the students, assessing how they were doing and whether they were taking an ADHD medication. This was now a naturalistic study much like the one that Martin Harrow had conducted of schizophrenia outcomes, and readers of this book, having become familiar with the scientific literature, can easily guess what is coming next. At the end of three years, Jensen and the others discovered that “medication use was a significant marker not of beneficial outcome, but of deterioration. That is, participants using medication in the 24-to-36 month period actually showed increased symptomatology during that interval relative to those not taking medication.”
³⁸

In other words, those on medications saw their core ADHD symptoms—the impulsiveness, the inattentiveness, the hyperactivity—
worsen
, at least in comparison to those not on drugs. In addition, those on meds had higher “delinquency scores” at the end of three years, which meant they were more likely to get into trouble in school and with the police.
³⁹
They were also now shorter and weighed less than their off-med counterparts, evidence that the drugs suppressed growth. These results told of a drug therapy causing long-term harm, and when the NIMH-funded investigators reported on six-year outcomes, the findings remained the same. Medication use was “associated with worse hyperactivity-impulsivity and oppositional defiant disorder symptoms” and with greater “overall functional impairment.”
⁴⁰

Controversy has long raged over whether ADHD is a “real” disease, but this study showed that when it comes to using stimulants to treat it, the controversy is moot. Even if ADHD is real, stimulants aren’t going to provide long-term help. “We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case,” said William Pelham from the State University of New York at Buffalo, who was one of the principal investigators. “There were no beneficial effects, none. In the short term, [medication] will help the child behave better, in the long run it won’t. And that information should be made very clear to parents.”
⁴¹

With any medication, there is a benefit-risk assessment to be made, and the expectation is that the benefit will outweigh the risks. But in this case, the NIMH found that over the long term there was
nothing
to be entered on the benefit side of the ledger. That leaves only risks to be tallied up, and so now we need to look at all the ways that stimulants can harm children.

Ritalin and the other ADHD medications cause a long list of physical, emotional, and psychiatric adverse effects. The physical problems include drowsiness, appetite loss, lethargy, insomnia, headaches, abdominal pain, motor abnormalities, facial and vocal tics, jaw clenching, skin problems, liver disorders, weight loss, growth suppression, hypertension, and sudden cardiac death. The emotional difficulties include depression, apathy, a general dullness, mood swings, crying jags, irritability, anxiety, and a sense of hostility toward the world. The psychiatric problems include obsessive-compulsive symptoms, mania, paranoia, psychotic episodes, and hallucinations. Methylphenidate also reduces blood flow and glucose metabolism in the brain, changes that usually are associated with “neuropathologic states.”
⁴²

Animal studies of stimulants are also cause for alarm. Repeated exposure to amphetamines, scientists at the Yale School of Medicine reported in 1999, caused monkeys to exhibit “aberrant behaviors” that remained long after the drug exposure had stopped.
⁴³
Various rat studies suggested that lengthy exposure to methylphenidate might cause dopaminergic pathways to become permanently desensitized, and since dopamine is the brain’s “reward system,” medicating the child may produce an adult with a “reduced ability to experience pleasure.”
⁴⁴
Scientists at Texas Southwestern Medical Center in Dallas found that “preadolescent” rats exposed to methylphenidate for fifteen days turned into anxious, depressed “adult” rats. The adult rats moved around less, were less responsive to novel environments, and showed a “deficit in sexual behavior.” They concluded that “administration of methylphenidate” while
the brain is still developing “results in aberrant behavioral adaptations during adulthood.”
⁴⁵

Such is the outcomes literature for Ritalin and other ADHD medications. The drugs alter a hyperactive child’s behavior over the short term in a manner that teachers and some parents find helpful, but other than that, the medications diminish a child’s life in many ways, and they may turn a child into an adult with a reduced physiological capacity to experience joy. And, as we’ll see later in this chapter, there is one other heartbreaking risk with stimulants that remains to be explored.

As recently as 1988, the year that Prozac came to market, only one in 250 children under nineteen years of age in the United States was taking an antidepressant.
⁴⁶
That was partly due to a cultural belief that youth were naturally moody and recovered quickly from depressive episodes, and partly because study after study had shown that tricyclics worked no better than placebo in this age group. “There is no escaping the fact that research studies certainly have not supported the efficacy of tricyclic antidepressants in treated depressed adolescents,” a
Journal of Child and Adolescent Psychopharmacology
editorial acknowledged in 1992.
⁴⁷

However, when Prozac and other SSRIs were brought to market and touted as wonder drugs, the prescribing of antidepressants to children took off. The percentage of children so medicated tripled between 1988 and 1994, and by 2002 one in every forty children under nineteen years of age in the United States was taking an anti-depressant.
⁴⁸
Presumably these drugs provide a short-term benefit to children and adolescents that the tricyclics fail to provide, but unfortunately, we can’t review the scientific literature to see if that is true because, as is widely acknowledged today, the literature is hopelessly poisoned. The trials were biased by design; the results that were published in the scientific journals didn’t square with the actual
data; adverse events were downplayed or omitted; and negative studies went unpublished or were spun into positive ones. “The story of research into selective serotonin reuptake inhibitor use in childhood depression is one of confusion, manipulation, and institutional failure,” the
Lancet
wrote in a 2004 editorial. The fact that psychiatrists at leading medical schools had participated in this scientific fraud constituted an “abuse of the trust patients place in their physicians.”
⁴⁹

However, a somewhat accurate picture of the merits of the drugs’ efficacy in children has emerged through a roundabout process. During the course of SSRI-related lawsuits, expert witnesses for the plaintiffs—most notably David Healy in England and Peter Breggin in the United States—got a look at some of the trial data, and they observed that the drugs increased the suicide risk. They spoke out about what they had found, and with an increasing number of anguished parents telling of how their children had killed themselves after going on an SSRI, the FDA was forced to hold a hearing in 2004 on this risk. That, in turn, led to a stunning admission by the FDA’s Thomas Laughren about the drugs’ efficacy in children. Twelve of the fifteen pediatric antidepressant trials that had been conducted had failed. The FDA, in fact, had rejected the applications of six manufacturers seeking approval to sell their antidepressants to children. “These are sobering findings,” Laughren confessed.
⁵⁰

The FDA did approve Prozac for use in children, as two of the three positive studies reviewed by Laughren had come from trials of this drug. But, as many critics have pointed out, from a scientific perspective, there is no reason to think that Prozac is any better than the other SSRIs. The percentage of children who responded to Prozac in the two positive trials was similar to the drug response rate in the twelve failed trials; Eli Lilly simply had been better at using biased trial designs to make it
appear
that its drug worked. For example, in one of the two Prozac trials, all of the children were initially put on placebo for one week, and if they got better during that period, they were excluded from the study. This helped knock down the placebo response rate. Next, the children who were randomized onto Prozac were evaluated for a week, and only those “who adapted well” to the drug were then enrolled in the study.
This helped increase the drug response rate. “Before the study even started,” explained Jonathan Leo, editor in chief of the journal
Ethical Human Psychology and Psychiatry
, “there was a mechanism in place to maximize any difference between the drug and placebo groups—the placebo group was preselected for
nonresponders
, while the drug group was preselected for
responders
.”
⁵¹
Yet, even with this extremely biased trial design, the Prozac-treated children still fared no better than the placebo group on self-rating scales or ratings by their parents. In addition, the trial failed to show efficacy for fluoxetine on its “primary endpoint,” and thus efficacy arose entirely from a secondary “improvement” scale filled out by the psychiatrists paid by Eli Lilly to run the trial.

Such was the record of efficacy produced by the SSRIs in pediatric trials for depression. Most trials failed to show any benefit, and Eli Lilly had to use a grossly biased trial design to make Prozac appear effective. In 2003, the Medicines and Healthcare Regulatory Agency (MHRA) in the United Kingdom essentially banned the use of SSRIs, except for fluoxetine, in patients under eighteen years old. English scientists then reviewed all the relevant data and reported in the
Lancet
that they supported “the conclusions reached by the MHRA.”
⁵²
The truth, explained the
Lancet
editors in an accompanying editorial, was that these drugs “were both ineffective and harmful in children.”
⁵³
Australian scientists chimed in with a similar review in the
British Medical Journal
, their article enlivened by descriptions of the shenanigans that American psychiatrists had employed to make the SSRIs look beneficial in the first place. The authors of the positive studies, they said, had “exaggerated the benefits, downplayed the harms, or both.” The Australians also reviewed Lilly’s fluoxetine trials in children and determined that the “evidence for efficacy is not convincing.” As such, they concluded that “recommending [any antidepressant] as a treatment option, let alone as first line treatment, would be inappropriate.”
⁵⁴

In the absence of any efficacy benefit, we are now left with the unhappy task of tallying up the harm done by the prescribing of antidepressants to children and teenagers. We can start with the physical problems. SSRIs may cause insomnia, sexual dysfunction, headaches, gastrointestinal problems, dizziness, tremors, nervousness,
muscle cramps, muscle weakness, seizures, and a severe inner agitation known as akathisia, which is associated with an increased risk of violence and suicide. The psychiatric problems they can trigger are even more problematic. Timothy Wilens and Joseph Biederman at Massachusetts General Hospital conducted a chart review of eighty-two children treated with SSRIs, and determined that 22 percent of the children had suffered an adverse psychiatric event. Ten percent had become psychotic, and another 6 percent manic. “One of the most disturbing adverse outcomes is a worsening of emotional, cognitive or behavioral symptoms,” they wrote. “These psychiatric adverse events to medication can be significantly impairing.”
⁵⁵
North Carolina psychiatrist Thomas Gualtieri determined that 28 percent of the 128 children and adolescents he treated with SSRIs developed some type of “behavioral toxicity.”
⁵⁶
Other physicians have told of their SSRI-treated younger patients suffering panic attacks, anxiety, nervousness, and hallucinations.

Those findings tell of children and adolescents being made sick by SSRIs, and that is over the short term. To appreciate the long-term risks, we can look at the problems that have cropped up in adults and in animal studies. If the children go off the medication, they can expect to suffer withdrawal symptoms, both physical and mental. Should they remain on the drugs for years, they are at high risk of becoming chronically depressed. They may also develop—as the American Psychiatric Association warns in one of its textbooks—an “apathy syndrome,” which “is characterized by a loss of motivation, increased passivity, and often feelings of lethargy and ‘flatness.’”
⁵⁷
There is also memory loss and cognitive decline to worry about, and, as we saw earlier, animal studies suggest that the drugs may cause serotonergic neurons to become swollen and misshapen.

First there was the ADHD explosion, and then came the news that childhood depression was rampant, and not long after that, in the late 1990s, juvenile bipolar disorder burst into public view. Newspapers
and magazines ran features on this phenomenon, and once more psychiatry explained its appearance with a story of scientific discovery. “It has long been thought in the psychiatric community that children could not be given a diagnosis of bipolar disorder until the mid-to-late teens, and that mania in children was extremely rare,” wrote psychiatrist Demitri Papolos, in his bestselling book
The Bipolar Child
. “But scientists in the research vanguard are beginning to prove that the disorder can begin very early in life and that it is far more common than was previously supposed.”
⁵⁸
Yet the rise in the number of children and adolescents with this diagnosis was so astonishing—a fortyfold increase from 1995 to 2003—that
Time
, in an article titled “Young and Bipolar,” wondered if something else might be going on.
⁵⁹
“New awareness of the disorder may not be enough to account for the explosion of juvenile bipolar cases,” the magazine explained. “Some scientists fear that there may be something in the environment or in modern lifestyles that is driving into a bipolar state children and teens who might otherwise escape the condition.”
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