NEW YORK CITY—Preliminary follow-up data from the groundbreaking MTA treatment trial of children with attention-deficit/hyperactivity disorder (ADHD) suggests that the benefits of the study's two most effective interventions—both of which included tailored dosages of methylphenidate—were largely maintained 10 months after the trial's end, researchers reported at the annual meeting of the American Association of Child and Adolescent Psychiatry. However, although the differences between the four treatment arms remained statistically and clinically significant in two key outcome domains—symptoms of ADHD and oppositional defiance—the differences were not meaningful for several other measures.

The trial, officially known as the Multimodal Treatment Study of Children with ADHD, sparked controversy in some quarters when its initial findings, published in December 1999, were misinterpreted as a blanket endorsement of pharmacotherapy over behavioral therapy. But although the new findings continue to suggest that, on average, children do not do as well with a comprehensive behavioral intervention as they do with a state-of-the-art medical management program or a combination of the two approaches, the study's primary investigators emphasized that the psychosocial components of treatment played a major role in successful outcomes, even for children in the medication management group.

"We did not test a pill, we tested a medication strategy" that included extensive doctor-patient interactions, noted Peter Jensen, MD, Professor of Psychiatry at Columbia University. "There was a support system built into that medication," representing, as Dr. Jensen put it, "the psychotherapy of pharmacotherapy." Indeed, for patients with comorbidities—who represent roughly 70% of ADHD patients, both in this trial and in typical community samples—psychosocial interventions are often crucial, he said.

"THE MOST EXTENSIVE EVER"

The seven-site study was launched in 1992 with the goal of determining whether state-of-the-art medical management, a similarly extensive behavioral therapy program, or the combination of the two offered significant advantages over standard community care. A total of 579 children, ages 7 to 10, were randomly assigned to one of the four interventions, which were administered for 14 months. Dr. Jensen described the trial's behavioral therapy arm as "the most extensive behavioral therapy ever put together under protocol," as it included not only intensive therapy but also parent training, teacher consultations, daily behavioral report cards, and even an eight-week summer treatment program. The medication arm was similarly detailed: Stimulant dose was meticulously titrated for each child, and patients had monthly meetings, averaging 30 minutes, with their physicians. Although two-thirds of subjects assigned to community care also received stimulants, their doses were typically lower (roughly 20 mg/d versus 30 mg/d for the medication group) and their office visits less frequent (two per year).

The trial's 14-month outcome data revealed that all four interventions reduced ADHD symptoms and oppositional/aggressive behavior, and improved scores on various functional and psychosocial measures. In general, the combined-treatment and medication-alone arms produced better outcomes than the other two treatments. However, only the combination therapy group showed "consistent evidence of superiority to the community comparison group over all of the major outcome domains," Dr. Jensen noted. Medication alone led to "whopping effects" for ADHD and oppositional symptoms but was less effective in other domains; behavioral therapy was superior to community care for only one of the 19 outcome variables. By the trial's end, about 15% to 18% of children in the combined or medication alone groups still met diagnostic criteria for ADHD, compared to a third of subjects in the other groups, Dr. Jensen said.

10 MONTHS LATER

At the end of the 14-month trial, the investigators held debriefing sessions with each family and provided tailored recommendations for continued treatment; parents, of course, were free to follow this advice or to seek other approaches. Follow-up assessments conducted 10 months later revealed that several key outcome trends observed at 14 months were still apparent at the later date, reported L. Eugene Arnold, MD, Professor Emeritus of Psychiatry at Ohio State University, in Columbus. Once again, all four groups showed improvements from baseline, and the combined-treatment and medication groups continued to have fewer ADHD and oppositional symptoms than did subjects in the behavioral and community care arms. As before, there was no meaningful difference in symptom levels between the combined and medication groups, or between the behavioral and community care groups. There was a trend toward intergroup differences with regard to negative ineffective discipline—a parenting measure devised in post hoc analyses—but these differences were not quite statistically significant. There were no intergroup differences in social skills or reading scores; at 14 months, combination treatment had been superior to community care for both of these domains.

Overall, these findings indicate that although the general pattern of group differences was still apparent at follow-up, "there was some deterioration [of benefits] in the medication and combined groups," noted Lily Hechtman, MD, Professor of Psychiatry at McGill University in Montreal. When the researchers looked at outcomes only for subjects who were on medication between the 14- and 24-month time points, they found that the relative benefits of the four interventions mirrored the data for the entire group, so that ADHD and oppositional symptoms were lowest in subjects who had received medication or combined therapy, and highest in the other two groups. However, when the analysis was restricted to children who were medication-free during the follow-up period, the benefits of medical management evaporated and subjects in this group were no better off than the behavioral therapy or community care groups.

DO COMORBIDITIES MATTER?

Other recent findings have yielded insights into which subgroups benefited most from treatment—and which patients were likely to comply with clinician recommendations. A four-way comparison between study participants who had ADHD alone and those who also had an anxiety disorder, a disruptive behavior disorder, or both, revealed that only children with ADHD and an anxiety disorder did well regardless of whether they received medication, behavioral therapy, or the combination. In contrast, children with "pure" ADHD did not respond well to behavioral therapy, Dr. Jensen reported. A more puzzling observation was that children with all three disorders responded better to medication management than they did to combined therapy or behavioral therapy alone. Taken together, these findings, if replicated, suggest that treatment may be most successful if targeted to a child's comorbidity profile, Dr. Jensen said.

Additional analyses have focused on the services that patients and their parents utilized during the follow-up period. For example, the researchers found that parents were most likely to comply with the suggestions offered at the debriefing sessions if they had prior experience with the recommended treatment or service, whether it was medication, mental health services, or school services. "It's not a completely dumbfounding finding," acknowledged Kimberly Hoagwood, PhD, Associate Director for Child and Adolescent Research at the National Institute of Mental Health (NIMH), in Bethesda, Maryland. But the results do have value in that they indicate who is most likely to follow through on treatment recommendations, she noted.

Many of the relevant odds ratios were quite high. For example, the odds ratio that a family would comply with recommendations for school services was about 5 if the family had previously utilized such services. A somewhat more surprising finding came from the trial's medication management arm. Here, compared to the community care group, the odds ratio was about 9 that families would follow through on recommendations for specialty mental health services. This suggests that "there are some complexities in what propels families to seek care," perhaps related to family motivation, their connection to the therapist, or the stigma of the relevant service, Dr. Hoagwood said.

STAY TUNED

Not only does the MTA trial remain the largest pediatric study ever conducted under the auspices of the NIMH, but it is slated to become the longest-running such study. Plans are already underway to extend the follow-up period to include 72-, 96-, and 120-month evaluations; the investigators' goals include determining the impact of initial treatment on the development of new symptoms and analyzing the cost/benefit ratios of each treatment.

—Peter Doskoch

Suggested Reading
A 14-month randomized clinical trial of treatment strategies for attention-deficit/ hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry.1999;56:1073-1086.

Return to table of contents