Three sets of findings resulted from this prospective longitudinal study of the MTA children into adolescence. Intent-to-treat analyses revealed no appreciable differences among the children based on their randomized treatment group assignment at 7–9 years of age. ADHD symptom trajectory in childhood, however, was a strong predictor of outcome at both 6- and 8-years. Finally, despite overall maintenance of improvement in functioning relative to baseline (pre-treatment), the MTA group as a whole was functioning significantly less well than the non-ADHD classmate sample (LNCG) recruited at 24-months. These findings provide evidence that the differential effects of the ADHD treatments, evident when the interventions were delivered, attenuated when the intensity of treatment was relaxed. To our knowledge, these findings are the first in the ADHD treatment literature to document, for a wide range of symptom and functioning outcomes, the sustained absence of long-term effects of an initial period of randomly assigned treatment (separate analyses of long-term effects on substance use, growth, and heart rate are in progress).
Our results suggest that the initial clinical presentation in childhood, including severity of ADHD symptoms, conduct problems, intellect, and social advantage, and strength of ADHD symptom response to any treatment, are better predictors of later adolescent functioning than the type of treatment received in childhood for 14 months. This conclusion follows from our analyses comparing the children's 6- and 8-year functioning on the basis of their prior ADHD symptom “latent class” membership, when children in “Class 2” were characterized by the strongest and most enduring decrease in ADHD symptoms between baseline and 36 months. Compared to children in Classes 1 and 3, Class 2 children also had better scores at baseline on a range of variables that included symptom severity, conduct problems, learning problems and IQ, social skills, and family characteristics conferring socioeconomic advantage (fewer marital break-ups and better financial picture). These findings reflect, in a clinical sample, the moderate degree of stability in relative rank ordering of children's behavior or personality also seen in non-clinical samples.30
Yet for most of the MTA children (those in Classes 1 and 2), functioning was still substantially improved over baseline levels, suggesting that sustained improvement (not normalization) relative to the child's initial presentation for treatment is achievable. Gains may be greatest for children with the least severe initial presentation,31
although severity of initial presentation such as co-occurrence of conduct problems may not drive which
treatment works best.2
It is tempting to conclude that intensive medication management beyond 14-months could have resulted in continued differences between the randomly assigned treatment groups. This assumption is partially based on our prior report that the MTA medication algorithm resulted in a greater reduction of symptoms than the community-provided medication treatment, suggesting that aspects of the MTA pharmacologic protocol (e.g., initial titration, monthly monitoring including input from teacher, higher dosing, TID dosing) may improve results over those of community care.2
In addition, in a previous multimodal treatment study where medication was carefully titrated and monitored for two years, treatment gains were maintained for the entire period.32
However, after 14 months the MTA became an uncontrolled naturalistic follow-up study and inferences about potential advantages that might have occurred with continued long-term study-provided treatment are speculation. Moreover, with one exception (math achievement), children still taking medication by 6 and 8 years fared no better than their non-medicated counterparts despite a 41% increase in the average total daily dose, failing to support continued medication treatment as salutary (at least, continued medication treatment as monitored by community practitioners). Additionally, failure to find better outcomes associated with continued medication treatment occurred despite the arrival of improved long-acting stimulant medications that more effectively produce the 12-hour/day coverage of the MTA medication algorithm. Dramatic increases in prescriptions for these medications, beginning with OROS-MPH (Concerta®) in 2000 followed by Adderall XR®, showed widespread and immediate acceptance of their use during the MTA follow-up period.33
Finally, a previous analysis of the MTA data through 3 years did not provide evidence that subject selection biases towards medication use in the follow-up period accounted for the observed lack of differential treatment effects.7
Thus, although the MTA data provided strong support for the acute reduction of symptoms with intensive medication management, these long-term follow-up data fail to provide support for long-term advantage of medication treatment beyond two years for the majority of children—at least as medication is monitored in community settings. Decisions about starting, continuing, and stopping medication may have to be made on an individualized basis, avoiding untested assumptions about continuing benefit, and using periodic trial discontinuations to check for need and benefit.
Indeed, long-term monitoring of children with ADHD may be wise given the pervasive differences in symptoms, functioning, and apparent need for services found between the MTA and LNCG samples in adolescence. In an effort to fully appreciate the MTA children's functioning as adolescents, we expanded the range of variables studied. These results showed that, although symptoms and impairment remained appreciably improved over baseline levels, normalization was generally not achieved. We found poorer performance for the MTA children as a group versus LNCG children for 91% of the variables. For example, although we replicated an expected decrease in parent- and teacher-rated symptoms of hyperactivity and impulsivity,34–36
the MTA children's scores on all of the ADHD symptom measures were still substantially higher than those of their former classmates. Standardized achievement test scores, teacher ratings of academic performance, and even grades earned in high school, were lower for the ADHD than for the LNCG group. The MTA children also had a twofold higher rate of grade retention. Rates of delinquency and arrest were higher in the ADHD sample, and psychiatric hospitalizations were more common, occurring for 10% of the ADHD sample versus only 1% of the LNCG (although this difference did not appear to be a function of increased rates of psychosis, mania, or hypomania, dispelling concerns that CNS stimulant treatment triggers such disorders at high rates37
In contrast to this pattern of lower functioning on average in the MTA vs. LNCG samples, only 30% of the MTA children fulfilled DSM-IV criteria for ADHD by the 8-year follow-up. This figure is low compared to some prior estimates of ADHD persistence in adolescence36, 38–39
and may be an underestimate that fails to consider age-appropriate symptom cut-offs. Indeed, arguments have been put forth that the symptom count thresholds developed for the diagnosis of ADHD in children may be overly stringent for adolescents and adults.40
Moreover, there is some evidence that remission of symptoms does not equate with recovery of function.35–36
For example, only modest associations were found between ADHD symptom reports and various measures of impairment in daily functioning across four separate ADHD samples spanning the elementary to early adulthood years.41
A comparison of diagnostic algorithms in relation to indicators of impairment was beyond the scope of this paper but would be a fruitful analysis to aid future nosology decisions, particularly with regard to developmental changes in these associations. Our results also lend some support to the idea that indicators of functioning (beyond symptoms) may be crucial, if not more important than measurement of symptoms, in the design and study of treatments for ADHD.41,42
Direct measurements of academic performance in school (specifically, grades earned as a reflection of homework completion, quiz and test performance), behavioral transgressions including office referrals, disciplinary actions and conflict with parents, and social dysfunction ultimately drive treatment-seeking behavior and probably mediate long-term outcome. Given the wide-ranging differences between the MTA and LNCG samples in variables that transcend the symptoms of ADHD, and their potential importance as treatment targets, future clinical trials may be forced to broaden narrow definitions of primary outcome variables.
Taken together, these 8-year findings point to a crucial need for development of treatments that are efficacious, accessible, and lasting for high school-aged youth with ADHD and their parents. The available literature on this topic is quite small and in need of innovation.43
Unfortunately, teenagers with ADHD are not easy to treat. There is the temptation, despite our failure to find long-term advantage of medication treatment, to somehow improve adherence to medication treatment. However, an under-recognized problem in the treatment of adolescent ADHD is the dramatic decline in medication adherence with the onset of adolescence.44–45
In the current study, 62% of the MTA children taking medication at 14-months (post-treatment) had stopped by the 8-year follow-up despite the advances in long-acting stimulant medications. This decline is important in the larger context of studies finding poor adherence, more generally, with stimulant treatment regimens.46
Thus, treatments may need to target motivational variables to encourage adolescent participation in non-pharmacologic interventions (as well as pharmacologic interventions that may be acutely effective for a given individual),47
and that also address continued family and school involvement.48
There are also data to suggest that periodic psychosocial treatments for 10 years are effective, including for diagnosis of ADHD (for the children in the Fast Track study with high externalizing behaviors at baseline).49
Whether these strategies assist parents and adolescents with motivation to maintain treatment, and whether these results would apply to children diagnosed with ADHD Combined Type, is a subject of future study.
Overall, the findings of this 6- and 8-year follow-up of the children in the MTA indicate that 1) treatment-related improvements for the children in the MTA are generally maintained, but differential treatment efficacy continues to be lost at and beyond 36-months; 2) initial patient characteristics and demographics and improved ADHD symptom response to any of the MTA treatments or to community care predicts high-school-aged functioning for a range of outcomes; 3) on average, children with Combined Type ADHD, despite having received 14-months of intensive, state-of-the-art behavior therapy or medication management, are functioning less well than their nonADHD age-mates across most indices of functioning. Some children were lost to follow-up, and their families were demographically disadvantaged. Thus, the MTA versus LNCG group differences that we observed may be underestimates. Our findings suggest that community treatments can improve ADHD symptoms and associated impairment, but even when preceded by intensive medication management and/or behavioral therapy for 14 months, continuing community interventions are unable on average to “normalize” children with ADHD. These findings apply to a range of symptom and functioning indices including delinquency, arrests, grade retentions and letter grades earned in school, and psychiatric hospitalizations that occur for an important minority of the sample. Hence, there is a practical need to pursue further research to develop and deliver more effective sustainable interventions, and to shift the emphasis in the field from reliance on ADHD symptoms as the key outcome of treatment to include measurement of impairments that bring families in for treatment and that are likely to mediate adulthood functioning.