Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression.

BACKGROUND: The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline. METHODS: Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. RESULTS: For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). CONCLUSIONS: In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.

Sexual maturation among youth with ADHD and the impact of stimulant medication.

OBJECTIVE: Evaluate the differences in achieving puberty between ADHD and non-ADHD participants and the effects of medication on that process among ADHD participants. PROCEDURE: A subset of participants with ADHD from the Multimodal Treatment study of ADHD (n = 342) were compared with respect to Tanner staging to participants from a comparison group without ADHD (n = 159) at the 36-month follow-up assessment. Further comparisons were made for Tanner stages and Auxology of the participants in the ADHD group who were always (n = 61), never (n = 56), newly (n = 74) and inconsistently (n = 116) treated with stimulants. RESULTS: No statistically significant differences in Tanner stages of sexual development were found between the ADHD and non-ADHD groups at the age of assessment (between 10 and 14 years of age) or among the ADHD medication subgroups, although a trend was observed for stimulant-associated delayed pubertal initiation using auxological analysis. CONCLUSION: Children with or without ADHD did not differ in Tanner stages at the 3-year follow-up assessment, and exposure to stimulant medication does not appear to affect sexual development within this age range.

Maternal perspectives on the return of genetic results: context matters.

The objectives of this study were to study maternal preferences for the return of their child's genetic results and to describe the experiences, perceptions, attitudes, and values that are brought to bear when individuals from different racial and cultural backgrounds consider participating in genetic research. We recruited women with diverse sociodemographic profiles to participate in seven focus groups. Twenty-eight percent of participants self-identified as Hispanic; 49% as White, non-Hispanic; and 21% as Asian or Asian American. Focus groups were conducted in English or Spanish and were audio-recorded and transcribed verbatim. Transcripts were analyzed using qualitative thematic methods. Results indicated that preferences and decisions regarding the return of results may depend on both research and individual contextual factors. Participants understood the return of results as a complex issue, where individual and cultural differences in preferences are certain to arise. Another key finding was that participants desired an interpersonal, dynamic, flexible process that accommodated individual preferences and contextual differences for returning results. Our findings indicate a need to have well-developed systems for allowing participants to make and change over time their choices regarding the return of their child's genetic results.

Patterns and predictors of adolescent academic achievement and performance in a sample of children with attention-deficit/hyperactivity disorder.

The current study examined predictors of academic achievement, measured by standardized test scores, and performance, measured by school grades, in adolescents (Mn age = 16.8) who met diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD)-Combined type in early childhood (Mn age = 8.5; N = 579). Several mediation models were also tested to determine whether ADHD medication use, receipt of special education services, classroom performance, homework completion, or homework management mediated the relationship between symptoms of ADHD and academic outcomes. Childhood predictors of adolescent achievement differed from those for performance. Classroom performance and homework management mediated the relationship between symptoms of inattention and academic outcomes.

Stability of Class II treatment with an edgewise crowned Herbst appliance in the early mixed dentition: Skeletal and dental changes.

INTRODUCTION: The objectives of this research were to assess skeletal and dental changes in patients with Class II malocclusion treated with the edgewise crowned Herbst appliance in the early mixed dentition and to measure the stability of treatment after a second phase of fixed appliance therapy. METHODS: Twenty-two patients (ages, 8.4 ± 1.0 years) with Class II Division 1 malocclusion treated consecutively with the edgewise crowned Herbst appliance in the early mixed dentition were studied. Lateral cephalograms were taken before Herbst treatment, immediately after Herbst treatment, and after a second phase of fixed appliance therapy. The results were compared with a control group of untreated Class II subjects selected from the Bolton-Brush study, matched by age, sex, and craniofacial morphology. A total of 37 sagittal, vertical, and angular cephalometric variables were evaluated. Changes in overjet and molar relationship were calculated. Changes due to growth were subtracted to obtain the net changes due to treatment. The data were analyzed by using analysis of variance (ANOVA) and the t tests. RESULTS: Overcorrection with the Herbst appliance resulted in an average reduction in overjet of 7.0 mm and a change in molar relationship of 6.6 mm. Several factors contributed to the change in overjet: restraint of the forward movement of the maxilla (0.4 mm), forward movement of the mandible (2.0 mm), backward movement of the maxillary incisors (3.7 mm), and forward movement of the mandibular incisors (0.9 mm). Skeletal changes together with a 3.1-mm backward movement of the maxillary molars and a 1.1-mm forward movement of the mandibular molars contributed to the changes in molar relationship. After the second phase of fixed appliance therapy, the change in overjet was reduced to 2.8 mm. Most of the remaining overjet corrections were contributed by the restraint of maxillary growth (2.8 mm). The mandible moved posteriorly by 1.6 mm, and the mandibular incisors moved forward by 0.2 mm. Change in molar relationship was reduced to 2.2 mm. The maxillary molars moved backward by 0.2 mm, and the mandibular molars moved forward by 0.8 mm. CONCLUSIONS: Overcorrection of Class II malocclusion with the edgewise crowned Herbst appliance in the early mixed dentition resulted in a significant reduction in overjet and correction of the molar relationship. A portion of the correction was maintained after a second phase of fixed appliance therapy because of the continuous restraint of maxillary growth and the dentoalveolar adaptations.

Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design.

BACKGROUND: Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace environment. METHODS: After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms. RESULTS: Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX. CONCLUSIONS: LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1.

Parental Agreement on ADHD Symptom-Specific and Broadband Externalizing Ratings of Child Behavior.

Mothers and fathers often disagree in their ratings of child behavior as evidenced clinically and supported by a substantial literature examining parental agreement on broadband rating scales. The present study examined mother-father agreement on DSM-based, ADHD symptom-specific ratings, as compared to agreement on broadband ratings of externalizing behavior. Using mother and father ratings from 324 children who participated in the Multimodal Treatment Study of Children with ADHD, parental agreement was computed and patterns of disagreement were examined. Mother-father ratings were significantly correlated. However, a clear pattern of higher ratings by mothers compared to fathers was present across ratings. Agreement on ADHD symptom-specific ratings was significantly lower than agreement for broadband externalizing behaviors or ODD symptoms. Of several moderator variables tested, parental stress was the only variable that predicted the discrepancy in ratings. Disagreement between parents is clinically significant and may pose complications to the diagnostic process.

Trajectories of Growth Associated With Long-Term Stimulant Medication in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To estimate long-term stimulant treatment associations on standardized height, weight, and body mass index trajectories from childhood to adulthood in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: Of 579 children with DSM-IV ADHD-combined type at baseline (aged 7.0-9.9 years) and 289 classmates (local normative comparison group [LNCG]), 568 and 258 respectively, were assessed 8 times over 16 years (final mean age = 24.7). Parent interview data established subgroups with self-selected Consistent (n = 53, 9%), Inconsistent (n = 374, 66%), and Negligible (n = 141, 25%) stimulant medication use, as well as patients starting stimulants prior to MTA entry (n = 211, 39%). Height and weight growth trajectories were calculated for each subgroup. RESULTS: Height z scores trajectories differed among subgroups (F = 2.22, p < .0001) and by stimulant use prior to study entry (F = 2.22, p < .001). The subgroup-by-assessment interaction was significant (F = 2.81, p < .0001). Paired comparisons revealed significant subgroup differences at endpoint: Consistent was shorter than Negligible (-0.66 z units /-4.06 cm /1.6 inches, t = -3.17, p < 0.0016), Consistent shorter than Inconsistent (-0.45 z units /-2.74 cm /-1.08 inches, t = -2.39, p < .0172), and the Consistent shorter than LNCG (-0.54 z units/+3.34 cm/ 1.31 inches, t = -3.30, p < 0.001). Weight z scores initially diverged among subgroups, converged in adolescence, and then diverged again in adulthood when the Consistent outweighed the LNCG (+ 3.561 z units /+7.47 kg /+16.46 lb, p < .0001). CONCLUSION: Compared with those negligibly medicated and the LNCG, 16 years of consistent stimulant treatment of children with ADHD in the MTA was associated with changes in height trajectory, a reduction in adult height, and an increase in weight and body mass index. CLINICAL TRIAL REGISTRATION INFORMATION: Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); https://clinicaltrials.gov/; NCT00000388.

DSM-V and the future diagnosis of attention-deficit/hyperactivity disorder.

In general, recommendations for the DSM-V and future diagnoses of psychiatric disorders include a dimensional approach to complement the standard categorical approach. For the assessment of attention-deficit/hyperactivity disorder (ADHD), dimensional approaches to supplement the rigid categorical approach of the DSM-IV abound. Historically, dimensions based on severity of symptoms of ADHD and severity of general psychopathology have been used. General dimensional approaches described by a workgroup organized by the American Psychiatric Association are reviewed to provide background and context for a discussion of old and new dimensional approaches to complement future categorical diagnosis of ADHD in the DSM-V.

A linguistic analysis of in-office dialogue among psychiatrists, parents, and child and adolescent patients with ADHD.

OBJECTIVE: The aim was to evaluate in-office discussions of ADHD and psychiatric comorbidities. METHOD: Naturally occurring interactions among 11 psychiatrists, 32 patients and their parents were recorded, with a focus on "complicated" patients (i.e., having or suspected to have >or= 1 psychiatric comorbidities and/or learning disabilities in addition to ADHD). Participants were interviewed separately post visit. Transcripts were analyzed using validated sociolinguistic methodologies. RESULTS: Some 62% of patients were male, with an average age of 12.5 years, and 79% had a family history of ADHD. Visits were psychiatrist-driven, focusing on medication management and school performance, leaving management of comorbidities largely unaddressed. Post visit, 78% of parents and psychiatrists disagreed on patients' "most concerning behavior." Parents most often reported concern about aggression and oppositionality. Psychiatrists and parents emphasized different aspects of patients' personality, using deficit- and strength-based models, respectively. CONCLUSION: Psychiatrists and parents interpreted the relationship between ADHD and comorbidities differently. The significant incidence of misalignment regarding worrisome behaviors warrants further exploration.

Evidence, interpretation, and qualification from multiple reports of long-term outcomes in the Multimodal Treatment Study of children with ADHD (MTA): Part II: supporting details.

OBJECTIVE: To review and provide details about the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published during the past decade as three sets of articles. METHOD: In the second of a two part article, we provide additional background and detail required by the complexity of the MTA to address confusion and controversy about the findings outlined in part I (the Executive Summary). RESULTS: We present details about the gold standard used to produce scientific evidence, the randomized clinical trial (RCT), which we applied to evaluate the long-term effects of two well-established unimodal treatments, Medication Management (MedMGT) and behavior therapy (Beh), the multimodal combination (Comb), and treatment "as usual" in the community (CC). For each of the first three assessment points defined by RCT methods and included in intent-to-treat analyses, we discuss our definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term varying from weeks to years, and qualification of the interim conclusions about long-term effects of treatments for ADHD based on many exploratory analyses described in additional published articles. CONCLUSIONS: Using a question and answer format, we discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD.

Evidence, interpretation, and qualification from multiple reports of long-term outcomes in the Multimodal Treatment study of Children With ADHD (MTA): part I: executive summary.

OBJECTIVE: To review the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published over the past decade as three sets of articles. METHOD: In a two-part article-Part I: Executive Summary (without distracting details) and Part II: Supporting Details (with additional background and detail required by the complexity of the MTA)-we address confusion and controversy about the findings. RESULTS: We discuss the basic features of the gold standard used to produce scientific evidence, the randomized clinical trial, for which was used to contrast four treatment conditions: medication management alone (MedMgt), behavior therapy alone (Beh), the combination of these two (Comb), and a community comparison of treatment "as usual" (CC). For each of the three assessment points we review three areas that we believe are important for appreciation of the findings: definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term, and qualification of the interim conclusions about long-term effects of treatments for ADHD. CONCLUSION: We discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD.

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment.

OBJECTIVES: Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults (18-55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92-111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS: The least squares mean (95% CI) treatment difference (SHP465 MAS-placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 [10.95, 27.63]; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4-16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo. CONCLUSIONS: SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants. Clinical trials registry: clinicaltrials.gov (NCT00202605; https://clinicaltrials.gov/ct2/show/NCT00202605 ).

A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design.

OBJECTIVES: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS-placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo. CONCLUSIONS: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.

The Qualitative Interview Study of Persistent and Nonpersistent Substance Use in the MTA: Sample Characteristics, Frequent Use, and Reasons for Use.

OBJECTIVE: To evaluate participants' perceptions about frequent use and reasons for substance use (SU) in the qualitative interview study, an add-on to the multimodal treatment study of ADHD (MTA). METHOD: Using the longitudinal MTA database, 39 ADHD cases and 19 peers with Persistent SU, and 86 ADHD cases and 39 peers without Persistent SU were identified and recruited. In adulthood, an open-ended interview was administered, and SU excerpts were indexed and classified to create subtopics (frequent use and reasons for use of alcohol, marijuana, and other drugs). RESULTS: For marijuana, the Persistent compared with Nonpersistent SU group had a significantly higher percentage of participants describing frequent use and giving reasons for use, and the ADHD group compared with the group of peers had a significantly higher percentage giving "stability" as a reason for use. CONCLUSION: Motivations for persistent marijuana use may differ for adults with and without a history of ADHD.

3-year follow-up of the NIMH MTA study.

OBJECTIVE: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. METHOD: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. RESULTS: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. CONCLUSIONS: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.

Secondary evaluations of MTA 36-month outcomes: propensity score and growth mixture model analyses.

OBJECTIVE: To evaluate two hypotheses: that self-selection bias contributed to lack of medication advantage at the 36-month assessment of the Multimodal Treatment Study of Children With ADHD (MTA) and that overall improvement over time obscured treatment effects in subgroups with different outcome trajectories. METHOD: Propensity score analyses, using baseline characteristics and severity of attention-deficit/hyperactivity disorder symptoms at follow-up, established five subgroups (quintiles) based on tendency to take medication at the 36-month assessment. Growth mixture model (GMM) analyses were performed to identify subgroups (classes) with different patterns of outcome over time. RESULTS: All five propensity subgroups showed initial advantage of medication that disappeared by the 36-month assessment. GMM analyses identified heterogeneity of trajectories over time and three classes: class 1 (34% of the MTA sample) with initial small improvement followed by gradual improvement that produced significant medication effects; class 2 (52%) with initial large improvement maintained for 3 years and overrepresentation of cases treated with the MTA Medication Algorithm; and class 3 (14%) with initial large improvement followed by deterioration. CONCLUSIONS: We failed to confirm the self-selection hypothesis. We found suggestive evidence of residual but not current benefits of assigned medication in class 2 and small current benefits of actual treatment with medication in class 1.

Effects of stimulant medication on growth rates across 3 years in the MTA follow-up.

OBJECTIVE: To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD. METHOD: Naturalistic subgroups were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms. RESULTS: The subgroup x assessment time interaction was significant for z height (p <.005) and z weight (p <.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naïve subgroups had z scores significantly >0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size. CONCLUSIONS: Stimulant-naïve school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound.

Delinquent behavior and emerging substance use in the MTA at 36 months: prevalence, course, and treatment effects.

OBJECTIVE: To compare delinquent behavior and early substance use between the children in the Multimodal Treatment Study of Children With ADHD (MTA; N = 487) and those in a local normative comparison group (n = 272) at 24 and 36 months postrandomization and to test whether these outcomes were predicted by the randomly assigned treatments and subsequent self-selected prescribed medications. METHOD: Most MTA children were 11 to 13 years old by 36 months. Delinquency seriousness was coded ordinally from multiple measures/reporters; child-reported substance use was binary. RESULTS: Relative to local normative comparison group, MTA children had significantly higher rates of delinquency (e.g., 27.1% vs. 7.4% at 36 months; p = .000) and substance use (e.g., 17.4% vs. 7.8% at 36 months; p = .001). Children randomized to intensive behavior therapy reported less 24-month substance use than other MTA children (p = .02). Random effects ordinal growth models revealed no other effects of initial treatment assignment on delinquency seriousness or substance use. By 24 and 36 months, more days of prescribed medication were associated with more serious delinquency but not substance use. CONCLUSIONS: Cause-and-effect relationships between medication treatment and delinquency are unclear; the absence of associations between medication treatment and substance use needs to be re-evaluated at older ages. Findings underscore the need for continuous monitoring of these outcomes as children with attention-deficit/hyperactivity disorder enter adolescence.

Treatment for ADHD: is more complex treatment cost-effective for more complex cases?

OBJECTIVE: To determine the cost-effectiveness of three alternative high-quality treatments for attention deficit hyperactivity disorder (ADHD) relative to community care (CC) and to determine whether cost-effectiveness varies with the presence of comorbid disorders. DATA SOURCES/COLLECTION: The study included 579 children ages 7-9.9 with diagnosed ADHD at six sites. Data for the study were distilled from administrative data and from interviews with parents, including estimates of the child's functional impairment. These analyses focus on changes in functional impairment over 14 months. STUDY DESIGN: The study involved a large clinical trial that randomized participants to one of four arms: routine CC, intensive medication management (MedMgt), multicomponent behavioral treatment, and a combination of behavioral treatment and medication. PRINCIPAL FINDINGS: We assessed the cost-effectiveness of the alternatives using costs measured from a payer perspective. The preferred cost-effective treatment varies as a function of the child's comorbidity and of the policy maker's willingness to pay. For pure (no comorbidity) ADHD, high-quality MedMgt appears likely to be cost-effective at all levels of willingness to pay. In contrast, for some comorbid conditions, willingness to pay is critical: the policy maker with low willingness to pay likely will judge MedMgt most cost-effective. On the other hand, a policy maker willing to pay more now in expectation of future costs savings (involving, for example, juvenile justice), will recognize that the most cost-effective choice for comorbid conditions likely involves behavior therapy, with or without medication. CONCLUSIONS: Analyses of costs and effectiveness of treatment for ADHD must consider the role of comorbidities.