The first clinical observations of the impact of stimulants on what was then called hyperactivity occurred in the late 1930s, at the dawn of modern psychopharmacology. Stimulants are both the crown jewel and the bane of child psychopharmacology. No medicine available to psychiatrists produces a more rapid and dramatic effect more safely than the proper dose of a stimulant to a patient with ADHD. Again and again, researchers have demonstrated the ability of stimulants to reverse the key symptoms of inattention, hyperactivity, and impulsivity with remarkable precision and relatively minor side effects. I routinely encourage my psychiatry trainees to witness this phenomenon directly by asking a family to bring in their child before he or she receives the usual daily dose. The trainee can experience firsthand the child who tears around the office, impulsively getting into everything but not staying with anything for long because the next unexplored item beckons. After administering the stimulant, the trainee can witness the transformation, which takes no longer than thirty minutes, as that same patient turns into a far more normal child-quieter, more polite, and able to stay on task.
At the same time, stimulants highlight many of the frustrations of child and adolescent psychiatrists and the patients and families with whom they work. They are not effective for everyone; although an 85 percent response rate is excellent for field, it leaves 15 percent who continue to suffer. In addition, although the effects are prompt, they are also transient. It is clear these medications do not change whatever lies at the core of ADHD; rather, they target its manifestations. Also, despite years of innovative research, how stimulants affect the course of this potentially devastating disorder over time is still uncertain.
Stimulants have proven highly effective for the management of acute ADHD symptoms. Furthermore, starting in the late 1990s, options have expanded not only in the types of formulations available for stimulants but also in nonstimulant alternatives for treating ADHD.
The late 1980s and the 1990s were a time of major attitude shifts concerning the use of stimulants for treating ADHD. Researchers convincingly demonstrated that ADHD could affect adolescents and adults as severely as it does younger children. In addition, conventional wisdom that ADHD was a problem limited to school hours yielded to empirical evidence that it also affects many other aspects of life, including leisure time activities, peer relationships, and home life. A broad consensus among researchers, clinicians, affected families, and patients called for more vigorous identification and treatment of ADHD. This has included both more intense treatment at any time, longer during each day, for more days of the week, and more weeks of the year, but also over time—into adolescence and even adulthood.
The two major classes of stimulants available in the U.S. are amphetamine and methylphenidate. Since stimulants first entered common use in the 1960s for treating hyperactivity, public attitudes about them have varied widely—from hailing them as miracle drugs to vilifying them as brain poisons. As is so often is the case, the truth lies somewhere in between.
Since 1989, use of stimulants in the U.S. has expanded greatly especially during the late 1990s. Although evidence suggests this is probably a good thing for children with ADHD, there is little question that it has resulted in problems of diversion and misuse. Parents contemplating giving a stimulant to their child must be aware of the controversies that accompany this class of drugs.
Methylphenidate and amphetamine are called stimulants because they activate parts of the brain. Studies in animals and adult subjects show that they have a variety of effects, including increased alertness and energy, decreased tiredness, and improved ability to tend to even dull and repetitive tasks without errors. These effects may be mediated by an increase in dopamine, a neurotransmitter involved in the reward centers of the brain.
Parents often ask why anyone would be silly enough to give a brain stimulant to a child who already has too much energy. This is a valid question, and one that again shows how essential it is to differentiate children from adults. In prepubescent children, stimulants enhance attention and focus as they do in adults, but actually tend to reduce physical activity and energy. This is true whether a child has ADHD or not, something not known until the late 1970s. Before that, clinicians mistakenly believed that stimulants were a good diagnostic tool for ADHD: If the child grew less active and more attentive, he must have ADHD. Occasionally, you may still find physicians who adhere to this antiquated belief, but it is simply not true. Diagnosis of ADHD takes a lot more than observing a child respond to a medication.
While every drug has some side effects, stimulants have several advantages:
They have a long history of use in children. Although there is still much to learn, clinicians have been using methylphenidate and amphetamine regularly in children and young adolescents since the 1960s, and these drugs have been studied more extensively than any other psychoactive drug prescribed for children. Studies have repeatedly shown them to be safe and effective for reducing ADHD symptoms.
Stimulants start and stop working quickly. The effects of immediate release formulations begin within twenty to thirty minutes and are essentially out of the body after a few hours. Any behavioral effects are gone by the next day.
Stimulants work for a remarkably high percentage of patients. Research suggests that between 85 to 90 percent of children with combined-type ADHD will respond to one of the available medications.
The benefits persist over time for the key symptoms of ADHD in properly diagnosed individuals. Patients do not grow tolerant to the stimulant effects and need higher and higher doses, as occurs in stimulant abuse.
Despite this, knowledge about stimulants is still incomplete. For example, most studies to date have focused on schoolaged boys, and only a few have studied medication effects beyond a few weeks. Worse, essentially nothing is known about the long-term benefits and problems of stimulant treatment for ADHD and how early treatment may affect adolescence and adulthood.
Given what is known, the continuing level of public wariness about stimulants is impressive. Early in 2005, the Canadian government abruptly withdrew Adderall XR from the market after analyzing reports of twenty deaths worldwide in children and adults taking this drug, often in combination with several others. Deaths of any sort are cause for concern, and there is clear evidence that people who abuse stimulants such as methamphetamine or cocaine put themselves at risk for heart problems and sudden death. But were these deaths the fault of Adderall? Interestingly, the U.S. FDA examined the same data in 2004 and concluded that Adderall was not a concern. In late 2005, after widespread protests from parents whose children had been deprived of a beneficial medication and upon further careful review of the data, Canada reversed its decision and reinstated Adderall XR.
In early 2006, the U.S. FDA revisited the possibility of sudden death associated with the use of stimulants, both methylphenidate and amphetamine. A panel of cardiovascular experts reviewed a small number of reported deaths (fewer than fifty in the past ten years) thought to have occurred as a direct or indirect result of a therapeutic dose of a stimulant. The panel recommended a “black-box warning”—the FDA’s mechanism for emphasizing especially worrisome side effects—arguing that patients and parents needed to know. Final action has yet to be taken by the FDA.
(In February 2006, an FDA advisory committee narrowly approved a recommendation in favor of requiring black box warnings on ADHD medications. In March 2006, another FDA advisory committee unanimously decided that black box warnings were not warranted on ADHD medications, recommending instead that medication guides be developed for use by patients, families, and medical practitioners.)
How should you and your prescribing doctor choose which stimulant is right for your child? In essence, it really doesn’t matter all that much. No reliable methods exist yet for pairing a specific type of stimulant medication to a particular patient, and general response rates are so high that usually the first choice has an excellent chance of success. As a result, many physicians have become comfortable with one particular type or formulation of stimulant and will probably prescribe that one for your child. Even so, if you have prior positive or negative experiences with a particular type of stimulant, let the physician know, so your concern can be part of the decision-making process.
Although stimulants are generally well-tolerated, they do have potential side effects, including appetite suppression and resulting effects on weight, slower growth rate (height), insomnia, rebound, tics, irritability, and cognitive blunting. These are side effects that can, at times, interfere with their efficacy and may require switching to a different type of medication.
Although stimulants work for 80 to 85 percent of those with ADHD, there has been a long-standing interest in other classes of medications that might also be beneficial. Such medications are used in a relative minority of cases, but they can be viable alternatives either for severe cases of ADHD or those for which stimulants otherwise prove unsatisfactory.
In 2002, the FDA endorsed a new medication, atomoxetine (Strattera), specifically for ADHD. Atomoxetine is not a stimulant; instead, it increases brain norepinephrine activity, as do several other antidepressants. The endorsement of atomoxetine for ADHD was striking for many reasons, not only because it was the first drug in the modern era to come to market specifically for a childhood mental disorder. The drug company also established its safety and efficacy for adolescents and adults with ADHD.
Atomoxetine works differently from stimulants, requiring several weeks of daily usage before its benefits are apparent and often showing increasing benefit even months later. It must be taken daily, and “holidays” are neither feasible nor desirable. The actual mechanism by which atomoxetine works is poorly understood. The medication’s big advantage is that it works more smoothly than stimulants, not only throughout the day and evening but also into the next morning. If morning routines are a major problem for a child, this medication may be worth considering.
The side effects of atomoxetine also differ from those of stimulants. It tends to be too sedating, sometimes causing daytime lethargy. Most common, however, are problems with nausea and vomiting. These problems decrease somewhat with twice-daily dosing and if taken with a meal. Like stimulants, when atomoxetine works, the benefits last over time, without having to increase the dose except to accommodate changes in weight.
Stimulants and other medications known to be effective for ADHD can be of great help in treating this potentially disabling disorder. If you have a young child just starting medication for ADHD, he or she may need treatment for many years, perhaps for life. As with all medications, it is important not to treat this casually. As parents and as physicians, it is too easy to get into the habit of assuming that everything is fine once a helpful medication is found, and simply continue doing what has worked before. It is imperative to reassess the situation with your prescribing doctor every few years to ensure that other needed services are in place, that the medication continues to work as it should, and that new side effects or other problems, such as drug diversion or abuse, are not occurring. This discussion with your doctor can also be an excellent opportunity to review changes in the field and learn about new options and emerging findings from a range of studies.
One of the most distressing aspects of ADHD is its persistence. It is easy to forget how devastating the disorder can be when a child is doing well or to allow old problems to sneak back into family life over months and years. The main focus should always be to help protect the child from the inattention, impulsivity, and resulting issues that are central to this disorder.
Adapted from Medicating Young Minds, by Glen R. Elliott, Ph.D., M.D., with Kate Kelly. (A Lynn Sonberg Book) 2006: Stewart, Tabori & Chang. Copyright © 2006 by Glen R. Elliott and Lynn Sonberg Book Associates.
For more information, visit the NRC’s Web site, www.help4adhd.org/documents/MedChart.pdf. To view draft medication guides for ADHD medications, including current information on side effects, go to www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107918.htm.
Glen R. Elliott, PhD, MD, is Chief Psychiatrist and Interim Outpatient Director at the Children’s Health Council and Emeritus Professor of Clinical Psychiatry at the University of California, San Francisco, where he served as Director of the Children’s Center at Langley Porter Psychiatric Institute from 1989 to 2006. A child and adolescent psychiatrist, Dr. Elliott has been an investigator in the Multimodal Treatment Study of Children with ADHD.