Agenda | Abstracts | Speakers | Research | Conclusions  

• William Pelham, Jr., Ph.D., State University of New York -- Buffalo  

• Laurence L. Greenhill, M.D., New York State Psychiatric Institute

William Pelham, Jr., Ph.D., State University of New York -- Buffalo

ADHD is one of the major mental health disorders of childhood, affecting 3% to 5% of children and accounting for a larger portion of referrals to mental health centers, special education, and behavioral visits to primary care physicians than any other childhood disorder. The symptoms of ADHD result in serious impairment for the child in many areas of functioning and skill development, including school, family, self, and peer domains that not only have a negative impact on the ADHD child but also result in dramatic burdens of care for parents and teachers. Unfortunately, ADHD children's difficulties do not disappear in childhood but instead continue, or even increase, through adolescence and into adulthood for the great majority of ADHD individuals. Among the most salient negative outcomes for ADHD adolescents and adults are problems with the justice system and alcohol and other drug abuse, which are public health problems of enormous import and cost to society. These areas of childhood impairment in ADHD--particularly with peers, schools, and family--not only highlight the seriousness of ADHD as a childhood problem but also predict the development of outcomes such as criminal behavior and alcoholism. Therefore, effective intervention for ADHD children is a major public health agenda both in terms of addressing a major childhood problem and with respect to the prevention of major public health problems of adulthood.

The purpose of this paper is to review what is known and not yet known about treatment for ADHD. It will focus on which treatments have an evidence base and which do not, and will highlight what is known about the utilization of treatments in classroom and community settings. A large number of treatments have been tried and are widely used for ADHD. However, the majority of them do not have evidence supporting their effectiveness. These include, among others, traditional one-to-one therapy, play therapy, cognitive therapy, restrictive or supplemental diets, allergy treatments, and biofeedback/neurotherapy.

Only three treatments have been shown to be evidence-based as effective short-term treatments for ADHD: (1) behavior modification; (2) central nervous system stimulants; and (3) the combination of (1) and (2) (Pelham, Wheeler, & Chronis, 1998; Swanson et al, 1995; Pelham & Wachsbusch, 1999). All of these treatments have been studied and used extensively for more than 25 years with ADHD children. The evidence base for their efficacy with ADHD is, therefore, quite large. Both medication and behavioral interventions have been shown to be effective in ameliorating acutely the symptoms and associated impairment in ADHD. Despite evidence for short-term efficacy, however, we do not have adequate knowledge of the long-term effects of either behavioral or pharmacological treatments.

Both behavioral and pharmacological treatments have limitations that mean that, alone, they are often insufficient treatments for ADHD. As a result of these limitations, combined or multimodal interventions have been the gold standard for ADHD treatment for the past decade. Studies of combined treatments generally reveal that such interventions are always absolutely and usually statistically superior to unimodal treatments. However, the most pressing questions about combined treatments for ADHD have not yet been addressed in the empirical literature and more research is needed (e.g., Which modality should come first? Can either treatment be faded? For how long should combined treatments be used? Can concurrent medication reduce the intensity and, therefore, the cost of behavioral treatments? Do the treatments work with very young ADHD children and with adolescents? Will improved long-term outcome result?).

Despite the evidence for their efficacy in studies, relatively little is known about the degree to which these three evidence-based treatments, as well as the other common but nonevidence-based treatments, are used in clinical and educational practice, as well as in family settings, and whether their use is appropriate. In addition, we know little regarding the effectiveness with which these treatments are utilized in nonresearch settings. This presentation will review such issues as the prevalence, accessibility, and utilization of evidence-based treatments for ADHD and examine whether findings differ as a function of such issues as treatment modality, treating professional, geographical location, and child/family characteristics. It will conclude with suggestions regarding steps that could be taken to increase the knowledge base regarding evidence-based treatments for ADHD.

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Laurence L. Greenhill, M.D., New York State Psychiatric Institute

Despite progress in the diagnosis, assessment and treatment of children with Attention-Deficit/Hyperactivity Disorder, treatment with psychostimulants remains an important public health concern, and one of the most controversial aspects of the disorder. Psychostimulants, including amphetamine (AMP), methylphenidate (MPH) and pemoline (PEM), have been proven effective in the short-term controlled studies for reducing ADHD symptoms, are readily available, and are prescribed frequently. Due to the lack of research data on the long-term (greater than 24 months) efficacy, safety and tolerability at the population level, a public health perspective should be applied to the treatment of children with ADHD. This has become all the more urgent because of growing prevalence estimates of the disorder, increasing production of MPH in the US, decreased age of initiation, and increasing duration of drug treatment during years of development. This change in treatment practice has occurred without evidence for long-term academic and functional improvements from stimulant treatment.

Stimulant prescribing for ADHD treatment in the United States has increased dramatically during the past five years. ADHD outpatient visits increased from 1.6 to 4.2 million per year during the years 1990-1993 (Swanson, Lerner, and Williams, 1995). During those visits, 90% of the children were given prescriptions, 71% of which were for MPH. During the same period production of MPH in the U.S. rose from 1,784 kg to 5,110 kg. Over 10 million MPH prescriptions were written in 1996 (Vitiello and Burke, 1998), and epidemiological surveys have estimated that the 12-month stimulant prescription prevalence for school-age children in the U.S. ranges 6% urban (Safer, Zito, and Fine, 1996) to 7% rural (Angold and Costello, 1997). Analyses of managed care datasets reveal a 2.5-fold increase in prescribing in the 1990-1995 time period, accounted for by longer durations of treatment, inclusion of girls and those with predominately inattention, and treatment of high school students (Safer, Zito, and Fine, 1996). Estimates suggest that by 1995, 2.8% of youth in the U.S. between the ages of 5 and 18 years were being prescribed MPH (Goldman and others, 1998). One survey in four different communities found that only one-eighth of diagnosed ADHD children were being treated with stimulants (Jensen and others, 1999), while another survey in rural North Carolina found one-third of the school-age children on stimulants did not meet diagnostic criteria for ADHD (Angold and Costello, 1997).

The reasons for the increased production and prescribing of MPH are unknown. Is the actual prevalence of ADHD increasing, are more cases now being identified by physicians, or are the standards for prescribing MPH changing? The risks involved in these changes are not known. On the one hand, a 1998 NIH Consensus Conference (NIH-CDC) found "wide variations in the use of psychostimulants across communities and physicians " (NIH Consensus Statement, 1998). Besides the lack of a definitive diagnostic test for ADHD, the NIH-CDC attributed this variability in practice to the absence of a well-understood, universally-accepted "ADHD diagnostic threshold above which the benefits of psychostimulant therapy outweigh the risks" (Kupfer and others, 1998). The NIH-CDC found a lack of consensus among U.S. practitioners regarding which ADHD patients should be treated with psychostimulants. On the other hand, the 1998 Council on Scientific Affairs of the American Medical Association concluded that "the risk-benefit ratio of stimulant treatment in ADHD must be evaluated and monitored on an on-going basis in each case, but in general is highly favorable (Goldman and others, 1998) ." At this stage, it is unclear whether the NIH-CDC’s increasing concerns about public safety or the AMA Council’s reassuring position is the more accurate point of view.

While both medications and behavioral therapies are effective interventions, the evidence favors medications for short-term symptom reduction, a conclusion consistent with a review by the McMaster University Evidence-Based Practice Center for the U.S. Agency for Health Care Policy Research (McMaster University Evidence-Based Practice Center, 1998) as well as with findings from the NIMH Multimodal Treatment of Children with ADHD (MTA) study (MTA Cooperative Group, 1999). Both sources report that combined behavioral and drug treatments offer modest advantages over medication treatments alone.

Stimulant-related side effects are dose related, occurring more often at higher doses. The NIH-CDC concluded that "there is no evidence that careful therapeutic use is harmful." This conclusion, based almost entirely on short-term (less than 14 months) data, may assist physicians responding to parental concerns. However, long-term studies of the effectiveness and safety of stimulant treatment in growing children have not been carried out to date and are very much needed.

It is not known whether stimulant use predisposes to later substance use. Given the fact that no fully experimental studies (e.g., parallel groups with random assignment, etc.) have been done in this area to date, and because the several available studies have come to different conclusions, it is difficult to disentangle the propensity for abuse from the ADHD condition itself vs. from its treatment with stimulants. But there is very little evidence to support the notion that current levels of production have had a substantial effect on abuse among high schoolers. Because of the ability of these compounds to produce addiction in laboratory animals when the compounds are given in very high doses, questions about their ability to produce addiction, tolerance, and sensitization during chronic treatment have arisen, but have not been answered conclusively.

Although psychostimulants are widely researched, research questions exist that have yet to be addressed. There are few data on the treatment of ADHD, inattentive type, which may include a large percentage of females. Second, pre-school children, adolescents, and adults are under-represented in published controlled clinical trials, even though they are increasingly being treated with stimulants. Third, there is limited safety information on sustained, long-term stimulant treatment (lasting longer than 14 months), even though current practice is to maintain drug treatment in children for years. Fourth, it cannot be determined if the combination of stimulants and behavioral treatments can improve functioning with a reduced drug dose.

More research is needed to determine the risks and benefits of early initiation of psychostimulant use in pre-school children. Despite a warning in MPH’s package insert against use in preschoolers, and reports of higher rates of adverse events in this younger age group, over 500,000 MPH prescriptions were written for preschoolers in 1998 (Greenhill, 1998). Because MPH acts primarily via the dopamine transporter protein (DAT), which undergoes active development during the preschool years, increased prescribing for these children is of great concern (Volkow and others, 1998). Little is known about the impact of MPH on brain development and risk for later illicit drug use. Once determined, the risks of early stimulant use need to be balanced against the known impairments of Attention Deficit Disorder on learning, social relations, and family functioning.

In what ways can CDC, as a public health agency, address these research needs at the population level? CDC could gather data about practitioners, provide grants to professional organizations to work with practitioners, and track the registry of insurance benefits. Furthermore, the agency could provide guidance on best practice for drug use by studying the risks and benefits of long-term stimulant interventions in the population, especially among pre-school children.

REFERENCES

Angold, A. & Costello, E. (In Press). Stimulant medication: A general population perspective: Psychopharmacology Bulletin, 1997.

Goldman, L., Genei, M., Bazman, R., & Stanetz, P. (1998). Diagnosis and treatment of Attention-Deficit / Hyperactivity Disorder. Journal of the American Medical Association, 279, 1100-1107.

Greenhill, L. (1998). The use of psychoactive medication in preschoolers: Indications, safety and efficacy. Canadian Journal of Psychiatry, 43, 576-581.

Jensen, P., Kettle, L., Roper, M., Sloan, M., Sloan, M., Dulcan, M., Hoven, C., Bird, H., Bauermeister J, & Payne, J. (1999). Are stimulants overprescribed? Treatment of ADHD in four U.S. communities. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 797-805.

Kupfer, D., Baltimore, R., Berry, D., Breslau, N., Ellinwood, E., Ferre, J., Fuchs, L., Guze, S., Hamburg, B., McGlothlin, J., Turner, S., & Vonnegut, M. (1998). Diagnosis and treatment of Attention Deficit Hyperactivity Disorder. NIH Consensus Statement. 1998. November 16-18. Journal of the American Medical Association, (In Press).

McMaster University Evidence-Based Practice Center, Anonymous. (1998). The treatment of attention-deficit/hyperactivity disorder: An evidence report (contract 290-97-0017). Washington, DC: Agency for Health Care Policy and Research.

MTA Cooperative Group. (1999). 14-month randomized clinical trial of treatment strategies for Attention Deficit Hyperactivity Disorder. Archives of General Psychiatry, (In Press).

NIH Consensus Statement. (1998) Diagnosis and treatment of attention deficit hyperactivity disorder. Nov 16-18. NIH Consensus Statement, 16.

Safer, D., Zito, J., & Fine, E. (1996). Increased methylphenidate usage for attention deficit hyperactivity disorder in the 1990s. Pediatrics, 98, 1084-1088.

Swanson, J., Lerner, M., & Williams, L. (1995). More frequent diagnosis of attention deficit-hyperactivity disorder. New England Journal of Medicine, 333, 944.

Vitiello, B. & Burke, L. (1998). Generic methylphenidate versus brand Ritalin: Which should be used?. Greenhill, L. & Osman, B. v. 2, (22):p. 221-226. Ritalin: Theory and Practice. Mary Ann Liebert, Inc. Larchmont, NY. (Abstract)

Volkow, N., Wang, G., Fowler, J., Gatley, S., Logan, J., Ding, Y., Hitzemann, R., & Pappas, N. (1998). Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. American Journal of Psychiatry, 155, 1325-1331.