MTA Study Research Articles

31.2 MINING THE MEANING OF THE MULTISITE MULTIMODAL TREATMENT STUDY OF ADHD (MTA) STUDY: NOVEL FINDINGS FROM QUALITATIVE STUDY METHODS

Most psychiatric research uses rigorously structured mental health interviews of DSM-based mental health disorders as well as paper-and-pencil questionnaires about study variables. Although these so-called “quantitative” study methods have generated important research findings, they have limitations. For example, although a given variable may be a causal factor for illness in some, the same variable can operate in the opposite manner in others; for example, taking a stimulant medication for ADHD might prevent substance abuse (SU) in some but precipitate it in others. Even diametrically opposed findings can be hidden in a study’s quantitative findings. In clinical practice, practitioners operate differently than quantitative researchers to understand illness. Like detectives who assemble clues after an event has occurred, clinicians seek to obtain a comprehensive history from various informants, gather clues regarding the patient’s beliefs and assumptions about the illness, and determine the most plausible explanation for the illness. Like clinical practitioners, qualitative researchers also use historical methods to understand patients’ beliefs and assumptions, in order to generate new hypotheses that can be verified by quantitative methods. We review a qualitative study of 183 patients’ interviews about their ADHD experiences via participation in the MTA and their beliefs and assumptions about ADHD, its causes, consequences, and optimal treatments. Despite over 150 quantitative research reports from the MTA study, questions persist. What explains the good vs poor outcomes of so many subjects? Why do some risk factors portend bad outcomes, but have no effect in others? How do “turning points” differentially affect the lives of youth, and how are these turning points linked to subsequent life decisions? Comparison of the MTA study’s quantitative vs qualitative findings reveals important new areas for study: some factors appear to convey “risk” in some but “benefit” in others. Some adults with ADHD cite the importance of turning points that led them to major life changes. For many, ADHD is seen as “no big deal,” and stimulants are seen as unnecessary. For some young adults, family factors are protective but are illness-producing for others.

31.1 VARIABLE PATTERNS OF REMISSION FROM ADHD IN THE MULTIMODAL TREATMENT STUDY OF ADHD (MTA)

It is estimated that childhood ADHD remits by adulthood in approximately 50% of cases; however, this conclusion is typically based on single endpoints, failing to consider longitudinal patterns of ADHD expression. We investigated the extent to which children with ADHD experience recovery and variable patterns of remission by adulthood. Children with ADHD (N = 558) in the MTA study were administered 8 assessments from 2-year (M age = 10.44 years) to 16-year follow-up (AI age = 25.12 years). We identified participants with fully remitted, partially remitted, and persistent ADHD at each time point based on parent, teacher, and self-reports of ADHD symptoms and impairment, treatment utilization, and substance use and mental disorders. Longitudinal patterns of remission and persistence were identified that considered context and timing. Approximately 30% of children with ADHD experienced full remission at some point during the 14-year follow-up period; however, a majority (60% of these) experienced recurrence of ADHD after the initial period of remission. Only 9% of the sample demonstrated recovery from ADHD by study endpoint, and only 10.8% demonstrated stable ADHD persistence across study time points. Instead, most participants with ADHD (64%) demonstrated fluctuating periods of persistence and remission over time. The MTA findings challenge the notion that approximately 50% of children with ADHD outgrow the disorder by adulthood. Most cases demonstrated fluctuating symptoms that may be environmentally modulated. Although 9% of children with ADHD continued to struggle with residual ADHD through young adulthood, intermittent periods of remission can be expected in most cases. We will share visual depiction of longitudinal and cross-sectional patterns of symptom remission, recovery, and persistence in the MTA, as well as case examples for patterns of recovery. These findings emphasize that childhood-onset ADHD is a chronic but waxing/waning disorder with periods of full remission that are more often temporary than sustained.

PROPAGATING PURITAN ISLAM IN SURAKARTA: READING THE BIOGRAPHY OF ABDULLAH THUFAIL SAPUTRA

Abdullah Thufail Saputra, a Pakistani-Javanese descendant, was one of the most influential figures in the spread of puritan da'wah in Solo in the 1970s and 1990s. He founded the Majlis Tafsir Al-Qur'an, which is now the largest and most massive Islamic organization in Solo. This study uses a qualitative approach. This study is complemented by essential elements such as observations, as well as in-depth interviews with some of Thufail's closest people. This study also examines some of the necessary documents, especially Thufail era brochures, MTA study recordings, and other documents. This article tries to explore Abdullah Thufail's intellectual journey, starting from his traditional educational background, changing his outlook from a traditional person to later becoming a Salafi-puritan, his missionary struggle, and how he founded and developed the MTA. This paper also discusses the struggle of MTA in accepting the sole principle of Pancasila and how MTA subsequently changed orientation after joining the New Order circle in 1984. The author also argues that the doctrine of zakat and jihad, which Thufail interpreted, became the central pillar for further MTA da'wah.

Editorial: Does a Diagnosis of Attention-Deficit/Hyperactivity Disorder in Childhood Determine an Increased Risk for Future Criminality?

Problems with occupational performance, emotional adjustment, legal involvement, and educational attainment are common in adults who had been diagnosed during childhood with attention-deficit/hyperactivity disorder.1 The National Institute of Health (NIMH) Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD) (MTA study) reported that of their cohort of 579 youth diagnosed with ADHD, combined type, age 7 to 9 years, half endorsed 4 persistent symptoms of ADHD when evaluated 16 years later at a mean age of 24.7 years.2 In fact, 41% persisted in meeting full ADHD symptomatic and impairment criteria as adults. This subgroup continued to experience problems with incomplete postsecondary education, job instability, lower current income, receipt of public assistance, and risky sexual behavior.3 Although the persistence of ADHD symptoms in the MTA study follow-up study was not associated with increased jail time, other studies concluded that a childhood diagnosis of ADHD was associated with a two- to threefold increased risk of later arrests, convictions, and incarcerations.4 Furthermore, although ADHD medications were not associated with better outcomes after 16 years of follow-up of the MTA cohort,5 Lichtenstein etal.6 reported that ADHD medication exerted a possible protective effect against incarceration.

0764 Changes In Sleep Patterns across Attention-deficit/hyperactivity Disorder Treatment: Findings from The MTA Study

0764 Changes In Sleep Patterns across Attention-deficit/hyperactivity Disorder Treatment: Findings from The MTA Study

Attention-deficit/hyperactivity disorder: seeking the right balance between over- and undertreatment

This issue of European Child and Adolescent Psychiatry contains an article that addresses functional impairments associated with subthreshold attention-deficit/hyperactivity disorder (ADHD) [2]. In a Korean nationwide community sample of 921 children, aged 8–11 years, the authors report that children with subthreshold ADHD were found to experience significant functional impairments, i.e., poorer behavioral and emotional control and worse academic performance compared to control children. Subthreshold ADHD was defined by the presence of at least three but no more than five inattentive or hyperactive/impulsive symptoms. However, whereas the diagnostic threshold (C6/9) for the DSM-IV symptoms represents a clear-cut operationalization for a diagnosis of ADHD, this disregards the fact that for the affected individuals and their parents the relevance of each symptom is likely to be different; for the diagnostic assessment as defined by the DSM-IV the symptoms are merely being counted, without taking the severity of each symptom into account. Furthermore, the subjective and objective impairment due to ADHD symptoms can in theory be greater in a child who fulfills only five symptoms in comparison to a child with six or more symptoms. These considerations illustrate how difficult it is to meaningfully operationalize thresholds for a spectrum disorder such as ADHD. It is certainly an interesting approach to illustrate impairments in a subthreshold version of a disorder that has received so much coverage by media, politicians, and government due to concerns about overdiagnosis and overtreatment with medication, in particular psychostimulants. The article of Hong et al. [2] in this issue illustrates that there is not a simple clear-cut boundary between ADHD and ‘normality’, which we should be well-aware of, when considering concerns of possible overdiagnosis. What is true, is that over the past decade, there has been a rapid and tremendous increase in the diagnosis of ADHD and in the use of medication treatments for ADHD within many European countries, in particular methylphenidate. This increase in the use of medication may be explained by several factors. First, better recognition and diagnosing of ADHD, in particular among girls. Second, the observation that children with ADHD receive the medication at a younger age than before. Third, it is now commonplace to receive the medication for many years, often during adolescent years and more and more into adulthood [4]. It is unclear, however, whether also children are being diagnosed and/or medicated in spite of falling below the diagnostic threshold set by DSM-IV (C6/9 criteria for either inattention or hyperactivity/impulsivity, or both) or failing to meet other aspects of the DSM-IV algorithm. A second issue is that the increased and longer use of methylphenidate contrasts with the lack of long-term data on effectiveness. In fact, for example, the official Dutch multidisciplinary guidelines explicitly state that there is currently only evidence for the long-term effectiveness of methylphenidate for treatment duration between 3 months and 2 years. Much of our knowledge about treatment periods of longer than a year comes from following up a single study, the Multimodal Treatment of ADHD study (MTA) [12]. Earlier reports from the MTA study found that children taking stimulants alone or combined with behavioral treatment did better in the first year than children who got no special care or who got behavioral treatment alone. Later long-term reports from the MTA study tracked 485 P. J. Hoekstra (&) A. Dietrich Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1-XA10, 9713 GZ Groningen, The Netherlands e-mail: p.hoekstra@accare.nl

Risques cardiovasculaires et conduite à tenir dans le traitement du trouble déficit de l’attention/hyperactivité avec le méthylphénidate

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common of the pediatric neuropsychiatric disorders. Methylphenidate is an important element of therapeutic strategies for ADHD. Clinicians are interested in the safety of methylphenidate. Because this drug raises heart rate and blood pressure, concerns have been raised about its cardiovascular safety. Concerns were based on case reports of sudden cardiac death in methylphenidate users, plausible pharmacological pathways involving well-established stimulant effects on heart rate and blood pressure. Until recently, data were limited to a number of observational studies too small to examine serious cardiac events. In the past two years, large retrospective, population-based cohort studies were performed. These studies did not show any evidence that methylphenidate was associated with an increase in risk of myocardial infarction, sudden cardiac death, or stroke. Treatment of children with methylphenidate is not significantly associated with an increase in the short term or mid-term risk of severe cardiac events. For many, available data now will be seen as reassuring. But gaps persist in the methodical and comprehensive assessments of the safety of methylphenidate. Analyses cannot be generalized to children with long-term use of stimulants. Furthermore, long-term effects of slight increases in heart rate or blood pressure are unknown. Stimulant administration continues to have a detectable adrenergic effect even after years of treatment. In the MTA study, greater cumulative stimulant exposure was associated with a higher heart rate at years 3 and 8. Although less severe, such adverse cardiac events are nonetheless alarming to patients. This adrenergic effect may have clinical implications, especially for individual patients with underlying heart abnormalities and it deserves further investigation. More research is necessary to optimize a safe use of methylphenidate regarding its cardiovascular effects. In light of the controversies surrounding the increase in the number of children being diagnosed with ADHD, the broad use of methylphenidate in these patients, and cardiovascular concerns about it, this article addresses topics of clinical significance. For ease of use by practitioners, the article summarizes the guidelines stated by the European Medicines Agency over the appropriate pretreatment evaluation and cardiovascular assessment. It advocates a thorough history and physical examination before initiating methylphenidate to treat patients with ADHD, with an emphasis on the identification of risk factors for sudden death. A cardiac sub-specialist consultation is mandatory in case of history or physical examination findings. In other cases, an electrocardiographic screening is recommended in order to check out previously unrecognized heart disease.

Does childhood positive self-perceptual bias mediate adolescent risky behavior in youth from the MTA study?

This study's primary aim was to examine whether the positive self-perceptual bias present in many youth with attention-deficit/hyperactivity disorder (ADHD; Hoza et al., 2004; Hoza, Pelham, Dobbs, Owens, & Pillow, 2002) mediates the relation of childhood ADHD status to later risky behaviors. Using a subset of children with ADHD and comparison children (n = 645) from the Multimodal Treatment Study of Children With ADHD, we predicted that a positive bias in childhood would partially or fully mediate the relation between having ADHD and risky driving and sexual behaviors 8 years later. Results strongly supported this hypothesis for risky driving behavior but only provided limited support for risky sexual behavior. Taken together, findings suggest that future research should explore whether self-perceptual bias may be a useful target of intervention for children with ADHD.

Evaluating long-term effects of a psychiatric treatment using instrumental variable and matching approaches

Evaluating treatment effects in non-randomized studies is challenging due to the potential unmeasured confounding and complex form of observed confounding. Propensity score based approaches, such as matching or weighting, are commonly used to handle observed confounding variables. The instrumental variable (IV) method is known to guard against unmeasured confounding if a good instrument can be identified. We propose to combine both methods to estimate the long-term treatment effect in a longitudinal psychiatric study. The NIMH collaborative Multi-site Treatment study of children with Attention-deficit/hyperactivity disorder (ADHD) compared different treatment strategies for children diagnosed with ADHD (known as MTA study). The first 14 months is a randomized study and the participants are allowed to choose their desired treatment strategies afterwards. Follow-up measurements are taken at 24, 36 and 72 months. Randomization is often considered as a good instrument since it is not associated with any covariate, observed or unobserved. We first apply a randomization based IV method to estimate the self-selected medication effect on outcome at the end of 72 months. However this approach yields results with huge standard errors due to randomization's weak relationship with later treatment selection. We then consider the self-selection right after the randomization as an instrument, because it is associated with later treatment selection and it is unlikely to affect the outcome directly given the five-year time lapse. To better control the confounding due to observed factors, propensity score matching is used to create a subpopulation with comparable covariate distributions across different self-selected treatments. Using MTA data, matching-enhanced IV estimation yields the most sensible result, while other estimation strategies tend to imply a spurious significant effect. Also, our simulation study shows that the matching-enhanced IV estimation outperforms non-matched methods in terms of relative bias.

ADHD Pharmacotherapy: Rates of Stimulant Use and Cardiovascular Risk

ADHD Pharmacotherapy: Rates of Stimulant Use and Cardiovascular Risk

Parent-Reported Homework Problems in the MTA Study: Evidence for Sustained Improvement with Behavioral Treatment

Parent-report of child homework problems was examined as a treatment outcome variable in the MTA–Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD). Five hundred seventy-nine children ages 7.0 to 9.9 were randomly assigned to either medication management, behavioral treatment, combination treatment, or routine community care. Results showed that only participants who received behavioral treatment (behavioral and combined treatment) demonstrated sustained improvements in homework problems in comparison to routine community care. The magnitude of the sustained effect at the 10-month follow-up assessment was small to moderate for combined and behavioral treatment over routine community care (d = .37, .40, respectively). Parent ratings of initial ADHD symptom severity was the only variable found to moderate these effects.

Short, Intensive ADHD Treatments are Not Long-Term Panacea

Short, Intensive ADHD Treatments are Not Long-Term Panacea

In This Issue/Abstract Thinking: The Costs of Mental Illness

Several articles in this month's issue of the Journal advance what is known about attention-deficit/hyperactivity disorder (ADHD). Articles by Molina et al. ( p. 484 ) and Jensen et al. ( p. 501 ) provide new analyses of the landmark NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA). In the original MTA study, 579 children between 7 and 9.9 years old were randomized to 14 months of either systematic medication management with methylphenidate, multicomponent behavior therapy, combined medication plus behavior therapy, or community care.

Common Behavioral and Learning Problems in Children an Alternative Nonmedical Approach: A Pediatrician’s Perspective

Primary care physicians, educators, and psychologists are faced with a virtual flood of children who are referred for evaluations for attention deficit disorder (ADD) or attention deficit/hyperactivity disorder (ADHD) and/or learning problems, most through their preschool or school. These children have been identified as having some combination of inattentive or impulsive behavior and underperforming academically in school. Many have been given a "screening test" in school and the results interpreted as suggesting ADD. Their parent(s) have been advised to get their child "tested" for ADD. This, of course, ignores the fact that there is actually no true test for ADD-only questionnaires describing relevant behaviors in subjective terms and results interpreted with arbitrary cutoffs to distinguish normal from supposedly disordered. My busy pediatric practice is no exception. I have faced the mounting pressure to diagnose and medicate increasing numbers of these children, all the while intuitively sensing that there must be a better way to help them than to rely on medical diagnoses and giving medication as the primary means by which they are enabled to restrain their behavior and to pay attention in school. This concern has increased when I am asked by a parent of a child who has been on stimulant medication for a number of years already, "Dr. Ravenel, when will we be able to stop [ Johnny's] medication?" My heart sinks because I know that a truthful answer to this question is that this child may well "need" to rely on his medication for an indefinite number of years, and with the now exploding diagnosis of "ADD" in adults, he may well never develop sufficient self-control and self-discipline without these medications. Furthermore, I know that I am presented with a dilemma to tell the parent that there is no reliable research on the potential risks from the long-term use of these medications if taken for years or even decades, as has become increasingly common. This lack of long-term properly designed scientific evidence for safety and effectiveness of methylphenidate (and other stimulants) has been noted by Australian researcher Natalie Sinn in her comments relating to her research on providing nutritional supplements to help with the behaviors that define ADD discussed later (Sinn, 2007). The two most frequent diagnoses I encounter with regard to otherwise normal children who display common problems of behavior and learning are ADD or ADHD and oppositional defiant disorder (ODD). The prevailing medical model for conceiving and managing these children assumes that there is a neurological or biological cause, with strong genetic influence, and effectively relies completely on psychotropic medications. Although this medical model for ADD gives lip service to the idea that one should "try behavioral methods first," in reality this is seldom done or, if it is done, relies on ineffective reward-based approaches. The flaws in interpretation of existing research that characterize the medical model and the logical and evidence base suggesting an alternative explanation for the causes of the behaviors that define ADD and ODD can be found elsewhere (Furman, 2005; Ravenel, 2002; Ruff, 2005). One of the most widely quoted research studies quoted by proponents of the prevailing medical approach is known as the "MTA study" (Multimodal Treatment Study for ADHD), widely accepted among prescribing practitioners as the "definitive" study to date. The behavioral approach used in this experimental project was so intensive and expensive as to be impractical for widespread application-yet even this rigorous attempt to manage these children without medication led to virtually no improvement in the core behaviors defining ADD. It is understandable that behavioral management of ADD and ODD behaviors is generally ignored or receives only token commitment. The prevailing rewardbased behavioral approach, modeled after that used by researchers in the MTA study, has been found inadequate for highly inattentive or misbehaving children. …

Research on Children Yielding Valuable Clinical Information

Research on Children Yielding Valuable Clinical Information

Preschoolers With ADHD May Benefit From Stimulants

Preschoolers With ADHD May Benefit From Stimulants

Cost-Effectiveness of ADHD Treatments: Findings From the Multimodal Treatment Study of Children With ADHD

Attention deficit hyperactivity disorder (ADHD) is a costly public health problem. To the authors' knowledge, this is the first study on the cost-effectiveness of the major forms of ADHD treatments used in NIMH's Multimodal Treatment Study of Children With ADHD (MTA Study). Five hundred seventy-nine children with ADHD, combined type, ages 7 to 9.9, were assigned to 14 months of medication management, behavioral treatment, both combined, or community care. Services were tallied throughout the study, including medication, health care visits, behavioral treatments, and rental costs. Provider specialty, total time, and number of visits with providers were used to calculate costs, adjusted to FY 2000 dollars with the consumer price index. Treatment costs varied fourfold, with medication management being the least expensive, followed by behavioral treatment, and then combined treatment. Lower costs of medication treatment were found in the community care group, reflecting the less intensive (and less effective) nature of community-delivered treatment. Medical management was more effective but more costly than community care and more cost-effective than combination treatment and behavioral treatment alone. Under some conditions, combination treatment (medical management and psychotherapy) were somewhat more cost-effective, as demonstrated by lower costs per additional child "normalized" among children with multiple comorbid disorders. Medical management treatment, although not as effective as combined medical management and behavioral treatment, is likely to be more cost-effective in routine treatment for children with ADHD, particularly those without comorbid disorders. For some children with comorbid disorders, it may be cost-effective to provide combination treatment.

Assessing medication effects in the MTA study using neuropsychological outcomes

While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures. 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau). Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability. This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.

Attention‐deficit hyperactivity disorder in a life perspective

Attention‐deficit hyperactivity disorder in a life perspective

Treatment Effects of Methylphenidate on Behavioral Adjustment in Children With Mental Retardation and ADHD

The effects of stimulant medication treatment were investigated in children with mental retardation (MR) and attention-deficit/hyperactivity disorder (ADHD). Parent and teacher behavioral ratings and reports of side effects were obtained for children (N = 24, mean age = 10.9 years, SD = 2.4) during a placebo-controlled, double-blind, crossover treatment trial with 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg b.i.d. dosages of methylphenidate. The most significant improvements occurred at the 0.60 mg/kg methylphenidate dose for teacher ratings of inattention (p =.024), hyperactivity (p <.001), aggression (p <.001), and asocial behavior (p =.009). No significant improvements, relative to placebo, occurred at the 0.15 mg/kg dosage. Of interest, nearly all significant medication-related behavioral improvements were detected by teachers. However, parents were sensitive raters of side effects, noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo. These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR, and consistent with MTA study results, higher doses were most effective. Furthermore, these improvements were not accompanied by increases in symptoms such as staring, social withdrawal, or anxiety.