Healthy Skepticism Library item: 8500

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Publication type: news

Ruff ME.
ADD and Stimulant Use: An Epidemic of Modernity
Medscape Pediatrics 2007 Feb 6
http://www.medscape.com/viewarticle/550918_1

Full text:

Success to Excess?
During my 14 years as a general pediatrician, I have always had a special interest in learning problems and attentional dysfunction. Stimulant medications have been a blessing, and I continue to use them in my practice for carefully chosen patients with great success. Over the past few years, however, I have become far more conflicted about the increased use of medication and about what has and has not been written in the mainstream pediatric literature on the phenomenology of attention-deficit/hyperactivity disorder (ADD). My professional vexation reached an epoch of sorts recently when I read an article stating that the popular television sitcom, “The Gilmore Girls,” had hired dialogue coaches to help the actors speak faster so they could hold their targeted “tween” audience’s attention more effectively.[1,2] The next morning I sat down with my mail before office hours. I chuckled under my breath because almost everything I received had something to do with ADD. There was a magazine entitled The ADHD Podium (sponsored by Shire and Adderall), which contained an article on how to use the DSM-IV criteria to diagnose and treat preschool children with ADHD. Next was a brochure and videotape from the University of Florida and Lilly (Strattera) on how to diagnose ADD in adults. Additionally, there were several faxes and letters offering to teach me more about the genetics, neurochemistry, and pharmacotherapeutics of ADD via dinner meetings and phone conferences. Finally, there were 3 magazines of different genres for my waiting room, all of which contained cover ads for Strattera boldly proclaiming: “Welcome to Ordinary” (via medication). By the time I was ready to pitch most of this in the trash and begin to see patients, my initial amusement had been replaced by bemusement. . . was my contemplation correct that the stimulant story had morphed from success to excess? Undoubtedly, the effectiveness of stimulant medication with heterogenous groups of individuals with academic and behavioral problems has encouraged wider boundaries in diagnosing ADD.³ Do the small cadre of influential academicians who do the vast majority of research and invited commentary want community pediatricians to conceptualize this as a genetically determined phenomenon and largely ignore the critical sociocultural underpinnings of this phenomenon? Is the pharmaceutical industry seducing us into subsuming broader diagnostic categories for ADD and thus expand their markets?

The belief that ADD is a biologically based condition is promulgated in the pediatric and psychiatric literature.[4-6] This is the premise on which the prolific researcher, Dr. Joseph Biederman, has based over 95% of his published articles.⁷ Many articles make reference to or examine ADD concordance in twins, neurochemical differences, mapping of loci, and structural brain differences seen on PET scan or functional MRIs. While ADD has a biologic substrate, the environmental contribution has been understated. For example, research on the structural differences in children’s brains with ADD has been purported to support the biological basis of ADD,⁸ and yet individuals with posttraumatic stress disorder (PTSD) also have significant structural differences in their brains compared with controls.[9-12] Therefore, one cannot conclusively distinguish between genetic and environmental etiologies when examining these structural differences. Gene-mapping studies have yet to yield any single loci or chromosomal region that is found consistently in the majority of individuals with executive dysfunction.¹³ The concordance rate for ADD has been quoted as approximately 40% in fraternal twins and 80% in identical twins.[14,15] If 1 parent has ADD, a child is purported to be 3 times more likely to have ADD and 10 times more likely if both parents have it.¹⁶ Yet, the dogmatic studies that make so much of the neurobiological contribution of ADD suffer from methodologic weakness that makes it difficult to separate out the effects of family heredity from family environment.¹⁷ In other words, the apple may not fall far from the tree. . . but, if the tree subsists with suboptimal soil and moisture, it will not produce good fruit. Research has shown, for example, that mothers who are intrusive, overstimulating, and isolated, with fewer emotional supports, are more likely to have children that are viewed by teachers and care providers as hyperactive and distractible between ages 3 and 8.¹⁸ In the words of Dr. Lawrence Diller, “Unfortunately researchers appear to be more interested in the environment of synapse than the environment of the child.”¹⁹

The Role of Environment and Culture
Only recently have scientists realized that learning itself is predicated on the continual switching of genes on and off. The more the lid is lifted off the genome, the more vulnerable to experiences genes appear to be. Experience influences upregulation and downregulation of gene expression. The fact that nature is designed for nurture has important implications for a balanced perspective on ADD and strongly suggests that executive function can be enhanced or damaged by experience. This concept, in its most basic form, is illustrated by the fact that monkeys have a predisposition to fear snakes and not flowers. However, you can teach monkeys to fear flowers and not snakes.²⁰ In one of the few studies on ADD and how the environment may alter expression of genes, Christakis and colleagues²¹ obtained data on television viewing for 1278 children at 1 year of age and 1345 children at age 3 years, while remarkably controlling for a wide variety of potentially confounding socioeconomic and demographic variables. One-year-olds watched an average of 2.2 hours of television per day while 3-year-olds watched an average of 3.6 hours per day. Overall, 10% of the children had attentional problems by age 7 years. Every standard deviation increase in the number of television viewing hours for an individual child was associated with a 28% increase in the risk of attentional problems at age 7 years.²¹ While these findings need confirmation, the Christakis study should serve as a springboard to investigate other related, yet largely unstudied aspects of our provocative, modern culture, and its permissive effect on genetic susceptibilities. If sufficient research in these areas is funded, it may likely confirm the hypothesis that our current cultural environment, rather than better awareness and more accurate diagnosis, is largely responsible for the ADD epidemic. Children today are inundated with more intense stimulation outside the classroom, and at an earlier age. Children are regularly assailed with the arousing special effects of ultrafast-moving and often-violent video games. Country Music Television (CMT), Music Television (MTV), and commercials often splice together images each tenth of a second. “The Gilmore Girls” speaking in hyperhaste to keep our attention and rapidly resolve a sitcom plot serves as a metaphor for our cultural addiction to speed — cell phones, faxes, beepers, Internet DSL, driving through McDonald’s. We are an impulsive, impatient culture with a free-floating sense of time urgency that feeds on rapidly changing trends, streaming ball scores and stock market data, deadlines, due dates, sound bites and megabytes. So why are so many kids immersed in this kind of culture rendered vulnerable? Why are they unable to attend, inhibit impulse, or seem bored in the classroom? What captivates, exhilarates, or keeps one’s attention is speed or the sensation of going faster. Brains need to feed on levels of stimulation to which they have acclimated. Listening to a teacher or doing a math problem is basically a waiting situation that provides a modern kid with a low level of stimulation. Distractibility, inattentiveness, and impulsiveness are essentially symptoms of boredom with the pace of the conventional classroom. Collectively, past generations were better poised and prepared to stay on task and attend in the classroom because of their life experiences outside the school. The pace of milking cows or reading for pleasure, the patience and analysis requisite for being a good marbles or jacks player, taught children deliberation, reflection, and attentional skills. This is in marked contrast to Play Station 2, which teaches a child to act on his first impulse or be blown up or eaten. Activities of past generations went relatively slowly and made the pace of the classroom more customary and, occasionally, more exhilarating.

Similarly, listening to “The Shadow” or a baseball game on the radio required kids to develop their own vibrant, visual mental imagery. Before MTV and CMT, kids listened to music and imagined the meaning of the lyrics or the emotion espoused by an enchanting rhythm. Now kids have a visual interpretation of a song passively presented to them. Children today are so unpracticed in this realm that they often lack the dimension of good reading or listening memory. This is because they are unable to generate the visual imagery necessary to augment what they have read or heard, and help get new information on long-term, retrievable memory hooks. Visual imagery skills also assist kids making rich associations with previously learned materials. This is both exciting and gratifying for a child. Education without excitement and gratification is boredom. An implicit part of the construct of boredom is inattention. Additionally, with television, there is a plot and rapid resolution. Reading generally requires a more disciplined abidement and illustrates how our current culture may mitigate against the development of good attentional skills.

These largely empiric observations of the impact of culture on attention are consistent with what is known about the adaptability and rewritability of the brain. The brain allocates neural real estate depending on what we use most; for example, mastering a foreign language or, for the thumb of a video game addict.²² The brain remakes and rewires itself based on what we do and think. In an analogous way to patching the strong eye of an amblyopia patient and making the weak eye better, it should be possible to alter our children’s environment to strengthen attentional function. This speaks to a possible strategy not only to treat ADD, but also to prevent it. It would be useful to conduct a study on eliminating television and video for select patients (impulsive subtype) as part of a multimodal treatment plan. However, these types of studies are difficult to fund.²³ Champions of the neurobiologically based diagnosis model have stated, “We would welcome rigorous studies of nonmedical therapies.”²⁴ Good studies, however, are unlikely immediately forthcoming because there is no money in them. Stimulant makers support studies that potentially edify and expand the genetic basis of ADD with multimillion-dollar grants. The drug companies are not interested in underwriting studies that may demonstrate a powerful contribution of the environment to this epidemic. Studies such as these, which raise awareness about prevention and treatment through environmental modification, would impact stimulant sales negatively.

Environments May Amplify or Mitigate Against Gene Expression
The incidence of ADD in Asian immigrants to this country is extremely low.²⁵ This is not because these people lack the genetic vulnerability, but rather is due to the protective effect of cultural values transmitted through the family. The love of learning and obedience is inculcated in these children.²⁶ Learning and imparting knowledge are taught to be perceived as pleasurable experiences rather than drudgery. Implicit in the concept of drudgery is inattention. The Indochinese immigrants have been immersed in video technology and our cultural tempo, but it is offset by the emphasis on family and discipline. As one study suggests, it takes more than 1 adversity to increase the risk for ADD.²⁷ Similarly, our small group private practice has over 800 Amish families and not a single child in this group has been referred to us by the schools for evaluation or recognized by us as having ADD. One culturally induced aspect of the ADD phenomenon, which the Amish don’t have to contend with, is medication use in the borderline cases to enhance performance. There is no doubt that significant amounts of stimulants are prescribed to aid the general struggle for success. Basic academic rigor occurs in Amish schools, but they are not pressured by competitive economic urgencies and expectations to achieve at high levels. In a local newspaper’s special feature on education in our Amish community, one non-Amish teacher remarked, “This is the greatest place in the world to teach. You don’t have to tell these kids twice. They do all their work. I like the respect the kids give you. That is taught by the parents.”²⁸ I have personally spoken with other non-Amish teachers in that community that echo those same sentiments. Notable, of course, is that this culture has no television or video games. The children also do physically demanding chores and often play outside. Physical exertion promotes mental exertion and good attentional function.[29-32] Though disparate in many ways, the Amish and Indochinese preserve family and cultural values that mitigate strongly against the expression of school problems.

It is also notable that exercise and lack of television protect the Amish population against obesity. Childhood obesity is essentially nonexistent in this patient population. Phenomenologically and phenotypically, there are striking parallels between the American epidemics of obesity and ADD. Hypervigilant hunters and gatherers, who were distracted by noise, thereby alerting them to potential dangers, conferred an evolutionary advantage in the same way a slow metabolism selects for survival during periods of famine. However, according to a recent editorial in Archives of Pediatrics, “Clearly genes related to obesity are not responsible for the epidemic of obesity because the United States gene pool did not change significantly over the last ten years.”³³

Perhaps because it may be deemed as heresy, similar statements in major pediatric journals about ADD are exiguous, even though teleologically it appears to be an identical phenomenon. If lifestyle modification is critical to both the treatment and prevention of obesity, it may also be of utmost importance for the prevention and management of ADD. Peter Jensen, lead investigator in the MTA study, stated, “I think we have to worry that we’re not doing enough to study the etiology of ADD — it cannot simply be the genes alone.”³⁴ These types of statements should not be relegated to arcane neuroscience and bioethics journals.

To use another culturo-anthropologic analogy, it is known that breast milk is not cariogenic. It is also known that human ancestors breastfed for 2 to 3 years and dental decay is never seen when ancient infant and toddler skulls are examined.³⁵ Early tooth decay became common with lifestyle change when sugar was introduced into our diet. Like for tooth decay, certain individuals are more susceptible to prefrontal lobe decay. Accordingly, genetic tendencies are at the mercy of our experience, and these observations support the assertion that the environmental contribution to the dimension of attention has been understated in the mainstream pediatric literature and that more research is needed.

Placing the Pendulum of Perspective in Better Balance
In addition to television and video games, how much of ADD is the brain’s maladaptive response to crowded classrooms, maternal smoking, iron deficiency, marital discord, or bad parenting?[36,37] These putative factors also need to be researched. The fact that neurobiology and psychopharmacology suffuse almost everything in the pediatric literature and the presentations at CME conferences unwittingly affords the general pediatrician with an unbalanced perspective. For example, the December 2003 issue of Contemporary Pediatrics was largely devoted to ADD. However, there was not a single mention of potential environmental contributions in the entire issue.³⁸ Likewise, in the lay literature, ADD is routinely referred to as a neurologic disorder or a chemical imbalance. The public tends to imbibe and apprehend this as biologic determinism whereby only heredity and brain chemistry determine behavior.²³ This perspective makes medication more easily justified and potentially marginalizes other interventions. Espousal of neurobiologic causes of ADD also satisfies parents craving for a brain-based explanation because it allays stigmatization and guilt. Nonetheless, the late Frank Oski stated there was nothing wrong with using guilt to try to modify parenting behavior.³⁹ Organizations such as CHADD [Children and Adults with Attention-Deficit/Hyperactivity Disorder] also desire a biological explanation because it serves to leverage ADD as a legitimate disability. Neurobiology “medicalizes” ADD and thus brings reimbursement from insurers and HMOs. Because behavioral issues are now such a large part of general pediatric practice, the stakes are high and we need to be afforded a more balanced perspective.

Increasing numbers of preschool children have been diagnosed with ADD in the last decade. In a recent Michigan Medicaid study, Rapley identified 223 kids aged 3 years or younger who received a diagnosis of ADHD; 60% received stimulant medication.⁴⁰ Eight published randomized controlled studies attest to the robust efficacy of stimulants in the preschooler.[41,42] We are bombarded with the promise of safe treatment in this age group by leading authorities.[43,44] Yet early childhood is a time of tremendous change for the developing brain. Cerebral metabolic rate and cortical synaptic density peaks at age 3 years and is substantially modified by pruning the next 7 years. Treatment with neuropsychiatric drugs in young rats alters lifelong levels of dopamine and norepinephrine.⁴⁰ Young adult monkeys exposed to just 2 doses of amphetamine (2 mg/kg) showed substantial decreases in striatal dopamine synthesis capacity and took up to 32 weeks to recover.⁴⁵ Thus, it would be prudent to pause before committing to treatment in this age group. Like a child who languishes because he is not exposed to adequate amounts of language at this critical developmental period, so too will kids struggle with behavior if they are not provided with the basic framework of security, discipline, and limit setting.

The Role of Parents and Schools
In 1970, it was estimated that 150,000 American children were taking stimulants.⁴⁶ Over 3 million US children currently take stimulant medication.⁴¹ Americans use 90% of the stimulants used worldwide. Stimulant use varies 5-fold among states and 20-fold in different communities within states. These facts lend support to the cultural hypothesis.⁴⁷ In the Great Smoky Mountain study, stimulant treatment was being used in ways substantially inconsistent with current diagnostic guidelines.[3,23] This implies that, to some extent, the ADHD diagnosis is being used as a maculate canopy to justify the use of stimulants for a wide range of performance and behavioral problems in children. The following case summary serves to illustrate this point.

Case Report
Jimmy, age 11, was brought to our office recently for a second opinion. His parents were divorced 4 years prior and their current relationship reportedly was adversarial. Jimmy had been on stimulant therapy for 3 years. His teachers reported that Jimmy had high-average general academic ability but was disorganized, performed inconsistently, had class work that was highlighted by impulsive and careless mistakes, frequently daydreamed, and, more recently, was noted to be confrontational and aggressive on the playground. His teachers noted that his problems were especially bad on Wednesdays and certain Fridays. Upon further questioning, Jimmy revealed that his father, to whom he felt close, had been through several live-in girl friends. Jimmy stated that his father didn’t pay attention to him when both he and his dad’s girlfriend were at the house. He added that, not long ago, his father’s infatuous relationship was so consuming that he completely forgot to pick him up at the prearranged time. This hurt Jimmy deeply. What Jimmy wanted to say at this point but couldn’t quite articulate was, “The emotional tension I’m feeling about my dad manifests as inattentiveness. My mind is consumed with these kinds of pressing concerns that render math and English relatively unimportant.”

Not long after convincing Jimmy’s parents to work together to better protect the positive feelings Jimmy had for both of them (no denigrating or criticizing the other parent in front of Jimmy), and persuading the father to spend some nights with Jimmy alone, his academic and behavioral performance improved significantly. Jimmy is currently off medication and doing well. Unfortunately, this is an exceptional case in that it is often very difficult to change parenting styles by giving advice in the office. It is also difficult for troubled families to take advantage of options such as behavior modification and parenting classes.[48,49] In many parts of the country, HMOs make it nearly impossible to even offer these therapeutic options. Thus, children are increasingly subjected to quick, inexpensive pharmacologic treatment as opposed to informed, multimodal therapy associated with optimal outcomes.⁴⁰

Time Spent With Parents
As stimulant use has rapidly escalated over the past 25 years, the amount of time that children spend with their biological parents has decreased by 40%.⁵⁰ A nationwide study of school principals found that regardless of income, educational failure and behavioral problems correlate more significantly with 1-parent households than with any other factors.⁵¹ There is a growing body of evidence showing that children who grow up under the tutelage of people other than their natural parents are more likely to fail in school.⁵² As we know, underperformance in school often results in a prescription.

Ten percent of the school-age population is classified as disabled.⁵³ The social needs of students have moved into the classroom, consuming scarce resources once allocated for education. The more children who are diagnosed as disabled, the fewer resources remain for the rest of the children — thus pushing the next kid teetering on the precipice into frank failure.⁵⁴ A teacher may see the positive effects of a stimulant on this borderline child and collective classroom function and then, given the pressure to produce results on standardized tests and deal with increased class size, have a lower threshold to refer the next child.⁵⁵ Stimulant drugs work well and often lull us into not making an assiduous effort to look for reading or other disabilities that may masquerade as an attentional problem, or to be complacent with dysfunctional family situations and overcrowded classrooms.²³ Treating a child may be individually expedient but societally dangerous. Medication may permit poor conditions to continue or worsen. By distributing 15 tons of stimulants per year, we may be aiding and abetting the burgeoning problems of overcrowded classrooms, overwhelmed teachers and parents, parental deficiencies in discipline skills, escalating academic standards, unreasonable expectations, and the continuance of a culture detrimental to the development of good attentional skills.⁵⁶ Have we been seduced into an over-reliance on pharmaceutical solutions to kids’ problems? The implications of this conundrum will take on even greater meaning in the near future as labs headed by investigators such as Eric Kandel and Timothy Tulley are tantalizingly close to perfecting drugs for memory enhancement. These drugs have superior efficacy compared with Aricept and Namenda, and will be on the market in 5 to 10 years.[57,58] Although these drugs will initially be approved for stroke victims, Alzheimer’s disease, and head trauma patients, this is the tip of the iceberg. “Drug companies won’t tell you this, but what they are really gunning for is the market of minimally and non-impaired people.”⁵⁸ Long ago, Rapoport⁵⁹ conclusively demonstrated that stimulants work well in children without attentional problems. Undoubtedly, there are many who take these drugs because they are struggling with the pressure to achieve or just keep up. Is the vociferous stance on the part of the medical community to ban performance-enhancing substances in sports due to the danger of steroids relative to stimulants, or is there a fairness issue as well?

Summary
The belief that ADD is a biologically based disease predominates the pediatric literature. However, this overemphasis on neurobiology has diminished the extremely relevant contributions of family dynamics, discipline, class size, economics, drug marketing, and cultural tempo. My fear is that in tacit response to this biological bombardment, many pediatricians unknowingly fail to seriously consider the environmental underpinnings of this complex diagnosis before writing a prescription.

This is not a call to discredit the diagnosis of ADD or stimulant therapy. But as pediatricians responsible for the collective welfare of our children, what does relying more and more on stimulants mean? Ours is a changing, complex world and there do not appear to be any simple answers. However, the following recommendations may serve as reasonable starting points:

Educate parents about preemptive strategies to deploy as part of early childhood anticipatory guidance — eg, the importance of exercise and limiting exposure to television and video games.

Advocate for tougher divorce laws. Currently, in many states it is easier to walk away from a marriage than to make a commitment to buy a used car.

Press for more thorough disclosure declarations by authors who research and write the majority of the ADD literature. The efforts of New York Attorney General Eliot Spitzer have led to legislation that makes it mandatory for CEOs and Boards of Directors to disclose salaries, options, and bonuses so that we can make more informed investment decisions. Likewise, researchers should be required to reveal just how much compensation, in the course of a year, they are afforded by companies such as Eli Lilly, Shire-Richwood, and Ortho-McNeil. We may then be able to better assess the merit of their conclusions and recommendations.

The American Academy of Pediatrics (AAP) should staunchly and more visibly advocate for studies on the environmental contributions to this epidemic. Unfortunately, the extensive recent practice parameter published by the AAP made only perfunctory mention of this need.⁶⁰ ADD is a public health issue and the AAP has the resources to effect real social change. For example, in response to articulate pleas from infectious disease experts, unnecessary antibiotic prescriptions have been significantly reduced.[61,62]

Finally, the balanced, perspicacious writings of authors such as Lawrence Diller, Mel Levine, and Stan Turecki should be required reading for anyone who prescribes stimulants.

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Michael E. Ruff, MD, FAAP, Clinical Associate Professor of Pediatrics,
Indiana University School of Medicine; Private Practice, Jasper Pediatric
Associates, Jasper, Indiana

Disclosure: Michael E. Ruff, MD, FAAP, has disclosed no relevant financial
relationships.