Stimulant treatment in children with attention-deficit/hyperactivity disorder moderates adolescent academic outcome

Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, the extent to which long-term academic gains are apparent in those having received such treatment remains elusive. This study examined prospectively the relationship of childhood stimulant treatment to academic functioning during adolescence. Children (n = 169) were initially recruited and diagnosed with ADHD when they were 7-11 years old. A subsample of those with childhood ADHD (n = 90) was reevaluated on average 9.13 (SD = 1.5) years later. Probands who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group (n = 80) on three subtests from the Wechsler Individual Achievement Test-II (WIAT-II), as well as high school grade point average (GPA) and number of retentions in school as derived from school records. Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that probands treated with psychostimulant medication achieved better academic outcomes, as measured by WIAT-II subtests and high school GPA, than those not treated with psychostimulants (p < .05). However, treated probands did not fare as well as the never-ADHD comparison group. Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance, although the extent of improvement is likely to vary as a function of multiple factors.     

Stimulant treatment of adult attention-deficit/hyperactivity disorder.

Though only recently recognized as a valid disorder in adults, the clinical picture of adult ADHD is highly reminiscent of childhood ADHD,with continued associated occupational failure and academic deficits. Similarly, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. Recent work clearly documents that when therapeutic doses of MPH and amphetamine treatment are used in the treatment of adults with ADHD, they can lead to a robust clinical response that is highly consistent with that observed in pediatric studies using equipotent daily doses. As in childhood ADHD, medication remains a key component of treatment for adults with ADHD. More studies are needed to evaluate the efficacy and safety of stimulants over the long-term and their impact on quality of life.     

Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder

OBJECTIVE: The purpose of this 13-study (seven double-blind/placebo-controlled, six open-label) meta-analysis is to determine the effectiveness and tolerability of long-term atomoxetine treatment among young children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Data were pooled from 6- and 7-year-olds (N = 272) who met DSM-IV criteria for ADHD, received atomoxetine treatment, and were enrolled in clinical trials of > or =2 years. Of these, 97 subjects reached the 24-month time point, providing data for long-term trend analysis of safety and effectiveness. RESULTS: Effectiveness for most subjects was maintained over long-term treatment, as demonstrated by total scores and total T scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version, investigator administered and scored. During the 2-year period, 25.7% discontinued because of lack of effectiveness, but adverse events were clinically minor and transient, and only 4.0% of children discontinued because of an adverse event. Notable effects on growth were seen during early phases of the study, with attenuation occurring by the 2-year time point. Statistically significant increases in pulse and blood pressure and decreases in cardiac PR interval were seen, but no changes were deemed both statistically significant and clinically meaningful among any vital signs, electrocardiographic measures, or laboratory tests. CONCLUSION: Long-term atomoxetine treatment appears generally well tolerated and effective in the treatment of young children with ADHD.     

Pharmacotherapy and academic achievement among children with attention-deficit/hyperactivity disorder

This study examined the association of pharmacological treatments and academic achievement among children with attention-deficit/hyperactivity disorder (ADHD). Results examining the association of pharmacological treatments and academic achievement among children with ADHD are mixed. Our objective was to examine this association using structural equation modeling (SEM) techniques, which may be considered more sophisticated and advanced over traditional regression techniques. To achieve the purpose, we employed a sample of children with ADHD derived from the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) data. The ECLS-K provides a large, community-based, nationally representative sample of children to examine across time with respect to academic achievement outcomes. The present study reveals a statistically nonsignificant association between pharmacological treatment and academic achievement among children with ADHD. These results derived from a large, community-based, nationally representative sample, using SEM techniques, may be considered highly generalizable.     

Aggression in children with attention-deficit/hyperactivity disorder

Research shows that aggression is an important associated feature of attention-deficit/hyperactivity disorder (ADHD) and is important in understanding the impact of the disorder and its treatment. The occurrence of aggressive behavior in combination with ADHD does not appear to be spurious and the severity and/or presence of aggression and ADHD may significantly impact long-term prognosis. This article defines subtypes of aggression in relation to ADHD, identifies individual differences contributing to aggressive behavior in children with ADHD and discusses selected possible underlying mechanisms of aggression in ADHD, as well as current and emerging treatment approaches. Although aggressive behavior in children with ADHD is common, the reasons for this are not yet well understood. Multidisciplinary research should focus on investigating underlying mechanisms related to aggression in ADHD, as well as the utility of various treatment modalities.     

A pilot study of atomoxetine in young children with attention-deficit/hyperactivity disorder

OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds. METHOD: Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit. RESULTS: Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p < 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p < 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p < 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children's Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p < 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p < 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy. CONCLUSION: Atomoxetine was generally effective for reducing core ADHD symptoms in the 5 and 6 year olds in this open-label study.     

Electrophysiological effects of stimulant treatment on inhibitory control in children with attention-deficit/hyperactivity disorder

OBJECTIVE: To examine the electrophysiological effects of methylphenidate (MPH) on inhibitory control in children with attention deficit/hyperactivity disorder (ADHD). METHOD: Twelve children with ADHD performed the Stop Signal Task (SST) while event related potentials (ERP) were obtained. Each child completed two testing sessions, once on placebo and again on an individualized dose of MPH, with the order of medication administration counterbalanced. The following ERP parameters were studied: the N200, often seen as a measure of the activation of the inhibitory process, and the NoGo-P3, which may represent the degree of performance monitoring and/or error detection. RESULTS: MPH significantly improved behavioral performance on the SST. During successful inhibitions, MPH also significantly increased the amplitude of the right frontal N200, while during unsuccessful inhibitions MPH increased the amplitude of the NoGo-P3. CONCLUSIONS: MPH may improve inhibitory control by enhancing brain mechanisms that trigger the inhibitory process and make stopping a motor act more probable (reflected by increased N200) and by increasing attentional resources to the task when unsuccessful inhibitions occur (as reflected by increased NoGo-P3). These results are consistent with functional imaging studies suggesting a role for the right frontal inferior cortex and the cingulate cortex in the pathophysiology of ADHD.     

Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder

A growing body of literature has examined the cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). However, a clear understanding of the types and magnitude of such effects are difficult to discern from such a large and varied collection of published reports. This review evaluated a total of 40 relevant placebo-controlled studies published since Rapport and Kelly's [1993. Psychostimulant effects on learning and cognitive function. In: Matson, J.L. (Ed.), Handbook of Hyperactivity in Children. Allyn & Bacon, Boston, pp. 97–136] original review of cognitive effects of methylphenidate in children with ADHD. Of these published studies, 63.5% identified some improvement in cognitive function following methylphenidate treatment. Methylphenidate improved performance on saccadic eye movement, planning/cognitive flexibility, attention/vigilance, and inhibitory control tasks in 83.3%, 71.4%, 70.6%, and 69.7% of studies, respectively. A total 58.3% and 50% of studies that evaluated the effect of methylphenidate on tasks of memory and working memory/divided attention, respectively, noted improvement. Variability of findings across studies may be explained by differential effects of methylphenidate on brain function, intra- and inter-individual variability in medication response, methodological limitations, and problems associated with repeated neuropsychological assessment and metric properties of commonly utilised neuropsychological instruments.     

Sleep disturbances in children with attention-deficit/hyperactivity disorder

In this article, we advocate the need for better understanding and treatment of children exhibiting inattentive, hyperactive, impulsive behaviors, by in-depth questioning on sleepiness, sleep-disordered breathing or problematic behaviors at bedtime, during the night and upon awakening, as well as night-to-night sleep duration variability. The relationships between sleep and attention-deficit/hyperactivity disorder (ADHD) are complex and are routinely overlooked by practitioners. Motricity and somnolence, the most consistent complaints and objectively measured sleep problems in children with ADHD, may develop as a consequence of multidirectional and multifactorial pathways. Therefore, subjectively perceived or reported restless sleep should be evaluated with specific attention to restless legs syndrome or periodic limb movement disorder, and awakenings should be queried with regard to parasomnias, dyssomnias and sleep-disordered breathing. Sleep hygiene logs detailing sleep onset and offset quantitatively, as well as qualitatively, are required. More studies in children with ADHD are needed to reveal the 24-h phenotype, or its sleep comorbidities.     

Chemosensory processing in children with attention-deficit/hyperactivity disorder

BackgroundIn attention-deficit/hyperactivity disorder (ADHD) not only deficits in dopamine-related cognitive functioning have been found but also a lower dopamine-sensitive olfactory threshold. The aim of the present study was to proof that only olfactory but not trigeminal sensitivity is increased in ADHD. Structural magnetic resonance imaging (MRI) was used to show increased olfactory bulb (OB) volume- a structure which is strongly shaped by olfactory performance through the mechanism of neuroplasticity (e.g. synaptogenesis). To elucidate whether cortical mechanisms are involved in altered olfaction in ADHD, functional MRI (fMRI) was introduced.MethodsA total of 18 boys with ADHD and 17 healthy controls (aged 7–12) were included in the study. Olfactory as well as trigeminal detection thresholds were examined. OB sizes were measured by means of structural MRI and an analysis of effective functional (fMRI) coupling of primary olfactory cortex was conducted. The frontal piriform cortex (fPIR) was chosen as seed region because of its importance in processing both trigeminal and olfactory stimuli as well as having profound influence on inner OB-signaling.ResultsIncreased olfactory sensitivity as well as an increase in OB volume was found in ADHD. There were no group differences in sensitivity towards a trigeminal stimulus. Compared to healthy controls, the fPIR in ADHD was more positively coupled with structures belonging to the salience network during olfactory and, to a lesser extent, during trigeminal stimulation.ConclusionsOlfactory functioning is superior in subjects with ADHD. The observed increase in OB volume may relate to higher olfactory sensitivity in terms of neuroplasticity. During the processing of chemosensory stimuli, the primary olfactory cortex in ADHD is differently coupled to higher cortical structures which might indicate an altered top-down influence on OB structure and function.     

Open-label amantadine in children with attention-deficit/hyperactivity disorder

OBJECTIVES: The purpose of this study was to explore the possible efficacy and tolerability of amantadine in the treatment of attention-deficit/hyperactivity disorder (ADHD) in stimulant-na?ve children. METHODS: Twenty four children (5-13 years old) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD (4 inattentive, 2 hyperactive, and 18 combined type) entered a 6-week open-label treatment with amantadine (50-150 mg) given as a single morning dose. Parent and teacher ADHD rating scales and the parent Child Behavior Checklist (CBCL) were administered at baseline and at week 6. RESULTS: Twenty three subjects completed the 6-week treatment. One child dropped out at week 2 because of persistent headache, and another 12 children reported adverse effects, most commonly transient appetite decrease. The parent ADHD score decreased from mean 41.04 +/- D 6.9 at baseline to 28.9 +/- 8.7 at week 6 (p < 0.001, effect size d = 1.5), and the teacher ADHD score from 35.8 +/- 9.6 to 26.2 +/- 9.5 (p < 0.001, effect size d = 1.0). Response rate (a 25% or greater decline in ADHD score) was 58% based on parents and 46% based on teachers. CONCLUSIONS: These data suggest that amantadine has acceptable acute tolerability at single doses up to 150 mg/day and is possibly efficacious in decreasing ADHD symptoms, although its activity appears to be more modest than that of stimulant medications.     

Psychopathology and substance abuse in parents of young children with attention-deficit/hyperactivity disorder

OBJECTIVE: To compare the prevalence of psychological disorders in parents of young children with and without attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behavior disorders (DBD). METHOD: Subjects included 98 three- to seven-year-old children with DSM-IV ADHD (68 with ADHD and comorbid oppositional defiant or conduct disorder [ADHD+ODD/CD]) and 116 non-ADHD comparison children recruited in 1995-96 during the first wave of a longitudinal study. Biological mothers were administered interviews to assess ADHD and DBD in their children and mood, anxiety, and substance use disorders in themselves. In addition, they were queried about symptoms of childhood ADHD and DBD, and antisocial personality disorder in themselves and their children's biological fathers. RESULTS: Child ADHD was associated with increased rates of maternal and paternal childhood ADHD relative to comparison children. Child ADHD+ODD/CD was associated with maternal mood disorders, anxiety disorders, and stimulant/cocaine dependence, and paternal childhood DBD. Mothers of children with ADHD+ODD/CD also reported increased drinking problems in their children's fathers. CONCLUSIONS: These findings indicate that many young children with ADHD, particularly those with comorbid ODD/CD, require comprehensive services to address both their ADHD and the mental health needs of their parents.     

Prior treatment with stimulant medication: a much neglected confounder of studies of growth in children with attention-deficit/hyperactivity disorder

Abstract Evidence is provided that growth is an accurate indicator of prior treatment with stimulant medication. This is of utmost importance when interpreting clinical studies on attention-deficit/hyperactivity disorder (ADHD), as pretreated cohorts are likely to include fewer nonresponders and fewer individuals with intolerable side effects. In this respect, growth patterns are an excellent tool to identify pretreatment and thus address selection bias.