Anatomy of an Epidemic (33 page)

Suddenly, ADHD children could be found in every classroom. The number of children so diagnosed rose to nearly 1 million in 1990, and more than doubled over the next five years. Today, perhaps 3.5 million American children take a stimulant for ADHD, with the Centers for Disease Control reporting in 2007 that one in every twenty-three American children four to seventeen years old is so medicated. This prescribing practice is mostly a U.S. phenomenon—children here consume three times the quantity of stimulants consumed by the rest of the world’s children combined.

Although the public often hears that research has shown that ADHD is a “brain disease,” the truth is that its etiology remains unknown. “Attempts to define a biological basis for ADHD have been consistently unsuccessful,” wrote pediatric neurologist Gerald
Golden in 1991. “The neuroanatomy of the brain, as demonstrated by imaging studies, is normal. No neuropathologic substrate has been demonstrated.”
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Seven years later, a panel of experts convened by the National Institutes of Health reiterated this same point: “After years of clinical research and experience with ADHD, our knowledge about the cause or causes of ADHD remains largely speculative.”
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During the 1990s, CHADD advised the public that children with ADHD suffered from a chemical imbalance, characterized by an underactive dopamine system, but that was simply a drug-marketing claim. Ritalin and other stimulants increase dopamine levels in the synaptic cleft, and thus CHADD was attempting to make it seem that such drugs “normalized” brain chemistry, but, as the American Psychiatric Press’s 1997
Textbook of Neuropsychiatry
confessed, “efforts to identify a selective neurochemical imbalance [in ADHD children] have been disappointing.”
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So we see in this history that nothing new was discovered that told of a “mental illness” called ADHD. There was a long record of speculation within medicine that extremely hyperactive children suffered from brain dysfunction of some kind, which was certainly a reasonable thought, but the nature of that dysfunction was never discerned, and then, in 1980, psychiatry simply created, with a stroke of its pen in DSM-III, a dramatically expanded definition of “hyperactivity.” The fidgety seven-year-old boy who might have been dubbed a “goof-off” in 1970 was now suffering from a psychiatric disorder.

Given that the biology of ADHD remains unknown, it is fair to say that Ritalin and other ADHD drugs “work” by perturbing neurotransmitter systems. Ritalin could best be described as a dopamine reuptake inhibitor. At a therapeutic dose, it blocks 70 percent of the “transporters” that remove dopamine from the synaptic cleft and bring it back into the presynaptic neuron. Cocaine acts on the brain in the same way. However, methylphenidate clears much more slowly from the brain than cocaine does, and thus it blocks dopamine reuptake for hours, as opposed to cocaine’s relatively brief disruption of this function.
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In response to methylphenidate, the child’s brain goes through a series of compensatory adaptations. Dopamine is now remaining in the synaptic cleft too long, and so the child’s brain dials down its dopamine machinery. The density of dopamine receptors on the postsynaptic neurons declines. At the same time, the amount of dopamine metabolites in the cerebrospinal fluid drops, evidence that the presynaptic neurons are releasing less of it. Ritalin also acts on serotonin and norepinephrine neurons, and that causes similar compensatory changes in those two pathways. Receptor densities for serotonin and norepinephrine decline, and the output of those two chemicals by presynaptic neurons is altered as well. The child’s brain is now operating, as Steven Hyman said, in a manner that is “qualitatively as well as quantitatively different from the normal state.”
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Now we can turn our attention to the outcomes data. Does this treatment help children diagnosed with ADHD over the long term? What does the scientific literature show?

Ritalin and other ADHD drugs do reliably change a child’s behavior, and in his 1937 report, Charles Bradley set the stage for the efficacy story that eventually emerged: “Fifteen of the thirty children responded to Benzedrine by becoming distinctly subdued in their emotional responses. Clinically in all cases this was an improvement from the social viewpoint.”
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Ritalin, which the FDA approved for use in children in 1961, was found to have a similar subduing effect. In a 1978 double-blind study, Ohio State University psychologist Herbert Rie studied twenty-eight “hyperactive” children for three months, half of whom were prescribed methylphenidate. Here is what he wrote:

Numerous investigators reported similar observations. Children on Ritalin show “a marked drug-related increase in solitary play and a corresponding reduction in their initiation of social interactions,” announced Russell Barkley, a psychologist at the Medical College of Wisconsin, in 1978.
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This drug, observed Bowling Green State University psychologist Nancy Fiedler, reduced a child’s “curiosity about the environment.”
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At times, the medicated child “loses his sparkle,” wrote Canadian pediatrician Till Davy in 1989.
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Children treated with a stimulant, concluded a team of UCLA psychologists in 1993, often become “passive, submissive” and “socially withdrawn.”
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Some children on the drug “seem zombie-like,” noted psychologist James Swanson, director of an ADHD center at the University of California, Irvine.
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Stimulants, explained the editors of the
Oxford Textbook of Clinical Psychophamacology and Drug Therapy
, curb hyperactivity by “reducing the number of behavioral responses.”
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All of these reports told the same story. On Ritalin, a student who previously had been an annoyance in the classroom, fidgeting too much in his or her chair or talking to a nearby classmate while the teacher scribbled on the blackboard, would be stilled. The student wouldn’t move around as much and wouldn’t engage as much socially with his or her peers. If given a task like answering arithmetic problems, the student might focus intently on it. Charles Bradley thought this change in behavior was “an improvement from the social viewpoint,” and it is that perspective that shows up
in efficacy trials of Ritalin and other ADHD drugs. Teachers and other observers fill out rating instruments that view a reduction in the child’s movements and engagement with others as positive, and when the results are tabulated, 70 to 90 percent of the children are reported to be “good responders” to ADHD medications. These drugs, NIMH investigators wrote in 1995, are highly effective in “dramatically reducing a range of core ADHD symptoms such as task-irrelevant activity (e.g., finger tapping, fidgetiness, fine motor movement, off-task [behavior] during direct observation) and classroom disturbance.”
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ADHD experts at Massachusetts General Hospital summed up the scientific literature in a similar way: “The extant literature clearly documents that stimulants diminish behaviors prototypical of ADHD, including motoric overactivity, impulsivity, and inattentiveness.”
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However, none of this tells of drug treatment that benefits the child. Stimulants work for the teacher, but do they help the child? Here, right from the start, researchers ran into a wall. “Above all else,” wrote Esther Sleator, a physician at the University of Illinois who asked fifty-two children what they thought of Ritalin, “we found a pervasive dislike among hyperactive children for taking stimulants.”
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Children on Ritalin, University of Texas psychologist Deborah Jacobvitz reported in 1990, rated themselves as “less happy and [less] pleased with themselves and more dysphoric.” When it came to helping a child make friends and sustain friendships, stimulants produced “few significant positive effects and a high incidence of negative effects,” Jacobvitz said.
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Other researchers detailed how Ritalin harmed a child’s self-esteem, as the children felt they must be “bad” or “dumb” if they had to take such a pill. “The child comes to believe not in the soundness of his own brain and body, not in his own growing ability to learn and to control his behavior, but in ‘my magic pills that make me into a good boy,’” said University of Minnesota psychologist Alan Sroufe.
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All of this told of harm done, of a drug that made a child depressed, lonely, and filled with a sense of inadequacy, and when researchers looked at whether Ritalin at least helped hyperactive children fare well academically, to get good grades and thus succeed as students, they found that it wasn’t so. Being able to focus intently
on a math test, it turned out, didn’t translate into long-term academic achievement. This drug, Sroufe explained in 1973, enhances performance on “repetitive, routinized tasks that require sustained attention,” but “reasoning, problem solving and learning do not seem to be [positively] affected.”
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Five years later, Herbert Rie was much more negative. He reported that Ritalin did not produce any benefit on the students’ “vocabulary, reading, spelling, or math,” and hindered their ability to solve problems. “The reactions of the children strongly suggest a reduction in commitment of the sort that would seem critical for learning.”
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That same year, Russell Barkley at the Medical College of Wisconsin reviewed the relevant scientific literature and concluded “the major effect of stimulants appears to be an improvement in classroom manageability rather than academic performance.”
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Next it was James Swanson’s turn to weigh in. The fact that the drugs often left children “isolated, withdrawn and overfocused” could “impair rather than improve learning,” he said.
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Carol Whalen, a psychologist from the University of California at Irvine, noted in 1997 that “especially worrisome has been the suggestion that the unsalutary effects [of Ritalin] occur in the realm of complex, high-order cognitive functions such as flexible problem-solving or divergent thinking.”
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Finally, in 2002, Canadian investigators conducted a meta-analysis of the literature, reviewing fourteen studies involving 1,379 youths that had lasted at least three months, and they determined that there was “little evidence for improved academic performance.”
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There was one other disappointment with Ritalin. When researchers looked at whether stimulants improved a child’s behavior over the long term, they couldn’t find any benefit. When a child stopped taking Ritalin, ADHD behaviors regularly flared up, the “excitability, impulsivity, or talkativeness” worse than ever. “It is often disheartening to observe how rapidly behavior deteriorates when medication is discontinued,” Whalen confessed.
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Nor was there evidence that staying on a stimulant led to a sustained improvement in behavior. “Teachers and parents should not expect long-term improvement in academic achievement or reduced antisocial behavior,” Swanson wrote in 1993.
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The 1994 edition of the APA’s
Textbook of Psychiatry
admitted to the same bottom-line
conclusion: “Stimulants do not produce lasting improvements in aggressivity, conduct disorder, criminality, education achievement, job functioning, marital relationships, or long-term adjustment.”
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Thirty years of research had failed to provide any good-quality evidence that stimulants helped “hyperactive” children thrive, and in the early 1990s, a team of prominent ADHD experts picked to lead a long-term NIMH study, known as the Multisite Multimodal Treatment Study of Children with ADHD, acknowledged that this was so. “The long-term efficacy of stimulant medication has not been demonstrated for
any
domain of child functioning,” they wrote.
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The NIMH touted its ADHD study as “the first major clinical trial” the institute had ever conducted of “a childhood mental disorder.” However, it was a rather flawed intellectual exercise right from the start. Although the investigators, led by Peter Jensen, associate director of child and adolescent research at the NIMH, acknowledged during the planning stages that there was no evidence in the scientific literature that stimulants improved long-term outcomes, they did not include a placebo control in the study, reasoning that it would have been “unethical” to withhold “treatment of known efficacy” for an extended period. The study basically compared drug treatment to behavioral therapy, but in that latter group, 20 percent were on a stimulant at the start of the trial, and there never was a time during the fourteen months that all of the children in that group were off such medication.
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Despite this obvious design flaw, the NIMH-funded investigators declared victory for the stimulants at the end of fourteen months. “Carefully crafted medication management” had proven to be “superior” to behavioral treatment in terms of reducing core ADHD symptoms. There was also a hint that the medicated children had fared better on reading tests (although not in other academic subjects), and as a result, psychiatry now had a long-term study that documented the continuing benefits of stimulants. “Since ADHD is
now regarded by most experts as a chronic disorder, ongoing treatment often seems necessary,” the researchers concluded.
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