White matter abnormalities associated with ADHD outcomes in adulthood.

It remains unclear if previously reported structural abnormalities in children with ADHD are present in adulthood regardless of clinical outcome. In this study, we examined the extent to which focal-rather than diffuse-abnormalities in fiber collinearity of 18 major white matter tracts could distinguish 126 adults with rigorously diagnosed childhood ADHD (ADHD; mean age [SD] = 34.3 [3.6] years; F/M = 12/114) from 58 adults without ADHD histories (non-ADHD; mean age [SD] = 33.9 [4.1] years; F/M = 5/53) and if any of these abnormalities were greater for those with persisting ADHD symptomatology. To this end, a tract profile approach was used. After accounting for age, sex, handedness, and comorbidities, a MANCOVA revealed a main effect of group (ADHD < non-ADHD; F[18,155] = 2.1; p = 0.007) on fractional anisotropy (FA, a measure of fiber collinearity and/or integrity), in focal portions of white matter tracts involved in visuospatial processing and memory (i.e., anterior portion of the left inferior longitudinal fasciculus, and middle portion of the left and right cingulum angular bundle). Only abnormalities in the anterior portion of the left inferior longitudinal fasciculus distinguished probands with persisting versus desisting ADHD symptomatology, suggesting that abnormalities in the cingulum angular bundle might reflect "scarring" effects of childhood ADHD. To our knowledge, this is the first study using a tract profile approach to identify focal or widespread structural abnormalities in adults with ADHD rigorously diagnosed in childhood.

A friendship intervention for children with Attention-Deficit/Hyperactivity Disorder: preliminary findings.

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are known to experience difficulty in peer relationships. Neither standard interventions for ADHD nor peer acceptance-oriented interventions fully remedy this problem. We propose that interventions targeting ADHD children's dyadic friendships may be more realistic strategies for improving peer relationships. Hence, a friendship intervention, implemented within the context of an intensive behavioral treatment program with 209 ADHD children, is described. A model is proposed in which the friend's antisocial behavior relates to parental compliance with the friendship intervention, and both the friend's antisocial behavior and parental compliance predict friendship quality and treatment response. Results indicate that children paired with peers lower on antisocial behavior and children whose parents had higher levels of compliance with the friendship intervention achieved higher quality friendships and were rated by teachers as more improved.

Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD.

The effects of methylphenidate on the academic performance and classroom behavior of 45 adolescents with attention deficit hyperactivity disorder were studied. During a 6-week, placebo-controlled medication assessment in the context of a summer treatment program, participants received a double-blind, crossover trial of 3 doses of methylphenidate. Dependent measures included note-taking quality, quiz and worksheet scores, written language usage and productivity, teacher ratings, on-task and disruptive behavior, and homework completion. Group data showed positive effects of methylphenidate on academic measures; however, the greatest benefit came with the lowest dose. Although additional benefit did occur for some participants with higher doses, the largest increment of change usually occurred between the placebo and 10-mg dose. Many adolescents did not experience added benefit with increased dosages, and in some cases they experienced deterioration. Guidelines for assessment of medication effects are discussed.

Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings.

OBJECTIVE: Methylphenidate (MPH), the most commonly prescribed drug for attention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces problems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting stimulants and preparations have shown effects equivalent to twice-daily dosing of MPH. This study tests the efficacy and duration of action, in natural and laboratory settings, of an extended-release MPH preparation designed to last 12 hours and therefore be equivalent to 3-times-daily dosing. METHODS: Sixty-eight children with ADHD, 6 to 12 years old, participated in a within-subject, double-blind comparison of placebo, immediate-release (IR) MPH 3 times a day (tid), and Concerta, a once-daily MPH formulation. Three dosing levels of medication were used: 5 mg IR MPH tid/18 mg Concerta once a day (qd); 10 mg IR MPH tid/36 mg Concerta qd; and 15 mg IR MPH tid/54 mg Concerta qd. All children were currently medicated with MPH at enrollment, and each child's dose level was based on that child's MPH dosing before the study. The doses of Concerta were selected to be comparable to the daily doses of MPH that each child received. To achieve the ascending rate of MPH delivery determined by initial investigations to provide the necessary continuous coverage, Concerta doses were 20% higher on a daily basis than a comparable tid regimen of IR MPH. Children received each medication condition for 7 days. The investigation was conducted in the context of a background clinical behavioral intervention in both the natural environment and the laboratory setting. Parents received behavioral parent training and teachers were taught to establish a school-home daily report card (DRC). A DRC is a list of individual target behaviors that represent a child's most salient areas of impairment. Teachers set daily goals for each child's impairment targets, and parents provided rewards at home for goal attainment. Each weekday, teachers completed the DRC, and it was used as a dependent measure of individualized medication response. Teachers and parents also completed weekly standardized ratings of behavior and treatment effectiveness. To evaluate the time course of medication effects, children spent 12 hours in a laboratory setting on Saturdays and medication effects were measured using procedures and methods adapted from our summer treatment program. Measures of classroom behavior and academic productivity/accuracy were taken in a laboratory classroom setting during which children completed independent math and reading worksheets. Measures of social behavior were taken in structured, small-group board game settings and unstructured recess settings. Measures included behavior frequency counts, academic problems completed and accuracy, independent observations, teacher and counselor ratings, and individualized behavioral target goals. Reports of adverse events, sleep quality, and appetite were collected. RESULTS: On virtually all measures in all settings, both drug conditions were significantly different from placebo, and the 2 drugs were not different from each other. In children's regular school settings, both medications improved behavior as measured by teacher ratings and individualized target behaviors (the DRC); these effects were seen into the evening as measured by parent ratings. In the laboratory setting, effects of Concerta were equivalent to tid MPH and lasted at least through 12 hours after dosing. Concerta was significantly superior to tid MPH on 2 parent rating scores, and when asked, more parents preferred Concerta than preferred tid IR MPH or placebo. Side effects on children's sleep and appetite were similar for the 2 preparations. In the lab setting, both medications improved productivity and accuracy on arithmetic seatwork assignments, disruptive and on-task behavior, and classroom rule following. Both medications improved children's rule following and negative behavior in small group board games, as well as in unstructured recess settings. Individual target behaviors also showed significant improvement with medication across domains in the laboratory setting. Children's behavior across settings deteriorated across the laboratory day, and the primary effect of medication was to prevent this deterioration as the day wore on. Results support the use of background behavioral treatment in clinical trials of stimulant medication, and illustrate the utility of a measure of individualized daily target goals (ie, the DRC) as an objective measure of medication response in both the laboratory and natural school settings. CONCLUSION: This investigation clearly supports the efficacy of the Concerta long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening. (ABSTRACT TRUNCATED)

Effects of methylphenidate and expectancy on performance, self-evaluations, persistence, and attributions on a social task in boys with ADHD.

This study examined the effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and persistence of 137 boys with attention-deficit/hyperactivity disorder (ADHD) in a get-acquainted dyadic interaction with a peer, using a balanced-placebo design. Boys in 4 groups-administered placebo or MPH crossed with being told they received placebo or MPH-interacted with child confederates in experimental situations in which social success and failure were manipulated. In contrast with studies of academic persistence, MPH did not affect boys' task persistence or performance. Boys gave more positive self-evaluations and talked more in the success condition as compared with the failure condition. Boys attributed success to effort and ability and failure to task difficulty, and neither MPH nor expectancy affected this pattern. These findings are consistent with other studies in failing to find debilitating effects of MPH or medication expectancies on ADHD boys' attributions or self-evaluations.

Behavioral versus behavioral and pharmacological treatment in ADHD children attending a summer treatment program.

As part of the behavioral treatment in the Multimodal Treatment Study of Children with ADHD (MTA9), children participated in an intensive summer treatment program (STP). This study examined the differences between 57 children in the combined treatment (Comb) group, who were medicated, and 60 children in the behavioral treatment (Beh) group, who were unmedicated throughout the STP. Comb children were significantly better than Beh on 5 measures: rule following, good sportsmanship, peer negative nominations, and STP teacher posttreatment ratings of inattention/overactivity. Groups did not differ on any of the other 30 measures, and responded similarly to the STP over time. Comparisons to normative data revealed that Comb children were more likely to fall within the normative range on 6 measures. The differences between these results and the main MTA results, in which Comb was always superior to Beh, are discussed in terms of the relative intensity of combined treatments. The implications for future studies of pharmacological and behavioral treatment for ADHD are discussed.

A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three times-daily methylphenidate in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: 1) To compare standard twice-daily methylphenidate (MPH) dosing with a single morning dose of MPH and of Adderall during a typical school-day time period, and 2) to conduct a dose-response study of the effects of a late-afternoon (3:30 PM) dose of MPH and Adderall on evening behavior and side effects. DESIGN: Within-subject, placebo-controlled, crossover design. SETTING: Intensive summer treatment program with a comprehensive behavioral approach. STUDY PARTICIPANTS: Twenty-one children with attention-deficit/hyperactivity disorder (19 boys and 2 girls), between the ages of 6 and 12 years. INTERVENTIONS: Children received, in random order with daily crossovers, each of the following conditions: 1) placebo, 2) 0.3 mg/kg of MPH received 3 times, 3) 0.3 mg/kg of MPH received twice (7:30 AM and 11:30 AM) with 0.15 mg/kg received at 3:30 PM, 4) 0.3 mg/kg of MPH received once in the morning only, 5) 0.3 mg/kg of Adderall received at 7:30 AM and at 3:30 PM, 6) 0.3 mg/kg of Adderall once in the morning with 0.15 mg/kg received at 3:30 PM, 7) 0.3 mg/kg of Adderall received in the morning only. OUTCOME MEASURES: Daily rates of behaviors in social and academic settings, and standardized ratings from counselors and teachers, were assessed for the hours between 8:00 AM and 3:30 PM (a typical school-day). Relative sizes of the medication effects were compared hourly between first daily ingestion (7:30 AM) and 4:45 PM to assess the time course of the 2 drugs. Effects of the 3:30 PM doses on functioning in the evenings at home were evaluated using parent ratings of behavioral and side effects. RESULTS: A single morning dose of Adderall produced equivalent behavioral effects to those of MPH received twice-daily and behavioral effects of that single morning dose lasted throughout the school-day period. One morning dose of MPH was less effective than either 2 daily doses of MPH or 1 dose of Adderall, and seemed to wear off in the early to mid-afternoon. For some children a single morning dose of MPH maintained their behavior for an entire school day in the context of the summer treatment program. On parent ratings of evening behavior, 0.3 mg/kg of MPH at 3:30 PM was superior to 0.15 mg/kg at 3:30 PM, but there was no difference between the 2 doses of Adderall. Compared with placebo at 3:30 PM, only the 0.3 mg/kg dose of MPH caused significant improvement in parent ratings. In placebo versus Adderall comparisons, all doses, even the condition that consisted of Adderall in the morning and placebo at 3:30 PM, produced a significant change in evening behavior. CONCLUSIONS: The results show that, at least in the context of an intensive behavioral intervention, a single morning dose of Adderall had behavioral effects throughout an entire school day period that were equivalent to standard twice-daily MPH dosing. These results indicate that Adderall may be used as a long-acting stimulant for children for whom midday dosing is a problem. Further study including dose-response comparisons, effects in regular school settings, and direct comparisons with comparable doses of MPH and d-amphetamine will help to clarify the time course and relative advantages of Adderall.

A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Very little research has focused on the efficacy of Adderall (Shire-Richwood Inc, Florence, KY) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD), and no studies have compared it with standardized doses of Ritalin (Novartis Pharmaceuticals, East Hanover, NJ). It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion. We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications' time courses. DESIGN: Within-subject, double-blind, placebo-controlled, crossover design lasting 6 weeks. As in our previous work, medication changes occurred on a daily basis in random order over days. SETTING: Eight-week, weekday (9 hours daily) summer treatment program at the State University of New York at Buffalo, using an intensive behavioral treatment program including a point system and parent training. STUDY PARTICIPANTS: Twenty-five children (21 boys and 4 girls) diagnosed as ADHD using standardized structured interview and rating scales, mean age 9.6 years, 88% Caucasian, of average intelligence, with no medical conditions that would preclude a trial of stimulant medication. Thirteen were comorbid for oppositional-defiant disorder and another 8 for conduct disorder. INTERVENTIONS: Children received 10 mg of Ritalin, 17.5 mg of Ritalin, 7.5 mg of Adderall, 12.5 mg of Adderall, or placebo, twice a day (7:45 AM and 12:15 PM), in random order with conditions changing daily for 24 days. OUTCOME MEASURES: Daily rates of behaviors in recreational and classroom settings, and standardized ratings from counselors, teachers, and parents, were averaged across days within condition within child and compared. Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo standard deviation for each child, and were compared hourly between first daily ingestion (7:45 AM) and 5:00 PM to assess the time course of the two drugs. Measures were taken at 12:00 PM (recess rule violations) and at 5:00 PM (parent behavior ratings) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off. Parent ratings were also made for evening behavior to assess possible rebound, and side effects ratings were obtained from parents, counselors, and teachers. Parents, counselors, and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day. Finally, a clinical team made recommendations for treatment taking into account each child's individual response. RESULTS: Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior, academic productivity, and staff/parent ratings of behavior. The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin, particularly the lower dose of Ritalin, on numerous but not all measures. This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin. Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening. The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin. Both drugs produced low and comparable levels of clinically significant side effects. Staff clinical recommendations for continued medication favored Adderall three to one. Almost 25% of the study participants were judged to be nonresponders by the clinical team, presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication. CONCLUSIONS: This is the first investigation to assess comparable doses of Adderall and Ritalin directly. (ABSTRACT TRU

Effects of deviant child behavior on parental alcohol consumption. Stress-induced drinking in parents of ADHD children.

Distress and ad lib alcohol consumption after interactions with child confederates were investigated in parents of children with externalizing disorders--attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD), or oppositional defiant disorder (ODD). Sixty subjects interacted with boys trained to act like either normal children or children with ADHD/CD/ODD. Interactions with deviant confederates resulted in feelings of inadequacy and produced negative affect but had no effect on alcohol consumption. Post hoc analyses showed that parents with a family history of alcohol problems (FH+) showed increased drinking after interaction with a deviant confederate, compared with FH+ parents who interacted with the normal confederate. FH- parents showed the opposite pattern of results.

Effects of deviant child behavior on parental distress and alcohol consumption in laboratory interactions.

Levels of adult distress and ad lib alcohol consumption following interactions with child confederates were investigated in parents of children with no diagnosable psychiatric disorders. Sixty parents (20 married couples and 20 single mothers) interacted with boys trained to enact behaviors characteristic of either normal children or "deviant" children with externalizing behavior disorders--attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD). Relative to the normal child role, interactions with deviant confederates were rated as significantly more unpleasant, resulted in feelings of role inadequacy, and produced significantly more anxiety, depression, and hostility. After the interactions, parents were given the opportunity to drink as much of their preferred alcoholic beverage as they desired while anticipating a second interaction with the same child. The participants consumed more alcohol following exposure to deviant as opposed to normal confederates.

Teacher ratings of DSM-III-R symptoms for the disruptive behavior disorders.

Ratings were collected on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders. Teacher ratings were obtained for 931 boys in regular classrooms in grades K through 8 from around North America. Means and standard deviations for attention-deficit hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), and conduct disorder (CD) scales are reported by age. Frequencies of DSM-III-R symptoms are reported by age, and suggested diagnostic cutoffs are discussed. A factor analysis revealed three factors: one reflecting ODD and several CD symptoms, one on which ADHD symptoms of inattention loaded, and one comprised of ADHD impulsivity/overactivity symptoms. Conditional probability analyses revealed that several hallmark symptoms of ADHD had very poor predictive power, whereas combinations of symptoms from the two ADHD factors had good predictive power. Combinations of ODD symptoms also had very high predictive power. The limited utility of teacher ratings in assessing symptoms of conduct disorder in this age range is discussed.

Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline.

Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind, placebo-controlled, crossover evaluation of the efficacy of standard methylphenidate twice a day and comparable doses every morning of a sustained-release preparation of methylphenidate (SR-20 Ritalin), a sustained-release form of dextroamphetamine (Dexedrine Spansule), and pemoline. The children were participating in a summer treatment program in which they engaged in recreational and classroom activities. Dependent measures include evaluations of social behavior during group recreational activities, classroom performance, and performance on a continuous performance task. Results revealed generally equivalent and beneficial effects of all four medications. Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication. The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion, and the effects lasted for 9 hours. The implications of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed.