Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial

OBJECTIVES: Evaluated the effects of atomoxetine on the reading abilities of children with dyslexia only or attention-deficit/hyperactivity disorder (ADHD) and comorbid dyslexia. METHODS: Children aged 10-16 years (N = 209) met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for dyslexia only (n = 58), ADHD and comorbid dyslexia (n = 124), or ADHD only (n = 27) and were of normal intelligence. Patients were treated with atomoxetine (1.0-1.4 mg/kg/day) or placebo in a 16-week, randomized, placebo-controlled, double-blind trial. The dyslexia-only and ADHD and comorbid dyslexia groups were randomized 1:1; the ADHD-only group received atomoxetine in a blinded manner. Reading abilities were measured with the Woodcock Johnson III (WJIII), Comprehensive Test of Phonological Processing (CTOPP), Gray Oral Reading Tests-4, and Test of Word Reading Efficiency. RESULTS: Atomoxetine-treated dyslexia-only patients compared with placebo patients had significantly greater improvement (p < 0.02) with moderate to approaching high effect sizes (ES) on WJIII Word Attack (ES = 0.72), Basic Reading Skills (ES = 0.48), and Reading Vocabulary (ES = 0.73). In the atomoxetine-treated ADHD and comorbid dyslexia group, improvement on the CTOPP Elision measure (ES = 0.50) was significantly greater compared with placebo (p < 0.02). Total, inattentive, and hyperactive/impulsive ADHD symptom reductions were significant in the atomoxetine-treated ADHD and comorbid dyslexia group compared with placebo, and from baseline in the ADHD-only group (p ≤ 0.02). ADHD symptom improvements in the ADHD and comorbid dyslexia group were not correlated with improvements in reading. CONCLUSIONS: Atomoxetine treatment improved reading scores in patients with dyslexia only and ADHD and comorbid dyslexia. Improvements for patients with dyslexia only were in critical components of reading, including decoding and reading vocabulary. For patients with ADHD and comorbid dyslexia, improvements in reading scores were distinct from improvement in ADHD inattention symptoms alone. These data represent the first report of improvements in reading measures following pharmacotherapy treatment in patients with dyslexia only evaluated in a randomized, double-blind trial

Acetyl-L-Carnitine in Attention-Deficit/Hyperactivity Disorder: A Multi-Site, Placebo-Controlled Pilot Trial

Objective: To determine whether acetyl-L-carnitine (ALC), a metabolite necessary for energy metabolism and essential fatty acid anabolism, might help attention-deficit/hyperactivity disorder (ADHD). Trials in Down’s syndrome, migraine, and Alzheimer’s disease showed benefit for attention. A preliminary trial in ADHD using L-carnitine reported significant benefit. Method: A multi-site 16-week pilot study randomized 112 children (83 boys, 29 girls) age 5-12 with systematically diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d. The 2001 revisions of the Conners’ parent and teacher scales (including DSM-IV ADHD symptoms) were administered at baseline, 8, 12, and 16 weeks. Analyses were ANOVA of change from baseline to 16 weeks with treatment, center, and treatment-by-center interaction as independent variables. Results: The primary intent-to-treat analysis, of 9 DSM-IV teacher-rated inattentive symptoms, was not significant. However, secondary analyses were interesting. There was significant (p = 0.02) moderation by subtype: superiority of ALC over placebo in the inattentive type, with an opposite tendency in combined type. There was also a geographic effect (p = 0.047). Side effects were negligible; electrocardiograms, lab work, and physical exam unremarkable. Conclusion: ALC appears safe, but with no effect on the overall ADHD population (especially combined type). It deserves further exploration for possible benefit specifically in the inattentive type

Prevention of serious conduct problems in youth with attention deficit/hyperactivity disorder

The purpose of this review is to discuss issues in the prevention of serious conduct problems among children and adolescents with attention deficit/hyperactivity disorder (ADHD). The authors began by reviewing research on the common genetic and environmental etiological factors, developmental trajectories, characteristics and impairments associated with ADHD and comorbid oppositional defiant and conduct disorders. Next, the authors presented empirically based models for intervention with children and adolescents with ADHD that are at risk of developing serious conduct problems and detailed the evidence supporting these models. Researchers have demonstrated the utility of medication and psychosocial intervention approaches to treat youth with these problems, but current evidence appears to support the superiority of multimodal treatments that include both approaches. Future directions for researchers are discussed

Negative Social Preference in Relation to Internalizing Symptoms Among Children with ADHD Predominantly Inattentive Type: Girls Fare Worse Than Boys

Despite distinct peer difficulties, less is known about the peer functioning of children with attention-deficit/hyperactivity disorder (ADHD) predominantly inattentive type (ADHD-I) in comparison to the peer functioning of children with ADHD combined type. Our purpose was to examine whether child sex moderated the relations between negative social preference and internalizing/externalizing problems in children with ADHD-I. Participants included 188 children diagnosed with ADHD-I (110 boys; ages 7-11; 54% Caucasian). Teacher ratings of the proportion of classmates who "like/accept" and "dislike/reject" the participating child were used to calculate negative social preference scores. Children, parents, and teachers provided ratings of anxious and depressive symptoms, and parents and teachers provided ratings of externalizing problems. Boys and girls did not differ on teachers' negative social preference scores. As hypothesized, however, the relation between negative social preference and internalizing symptoms was moderated by sex such that negative social preference was consistently and more strongly associated with internalizing symptoms among girls than in boys. In terms of externalizing problems, negative social preference was associated with teacher (but not parent) ratings, yet no moderation by child sex was found. Negative social preference is associated with teacher-report of externalizing problems for both boys and girls with ADHD-I, whereas negative social preference is consistently associated with girls' internalizing symptoms across child, parent, and teacher ratings. Implications for future research and interventions are discussed

Predictors of Response to Behavioral Treatments Among Children With ADHD-Inattentive Type

The goal of the study was to examine baseline characteristics-child gender, IQ, age, internalizing problems, symptoms of hyperactivity/impulsivity (HI), oppositional defiant disorder, and sluggish cognitive tempo, and parent income, education, attention deficit/hyperactivity disorder (ADHD) severity, and anxiety/depression (A/D)-associated with response to behavioral treatments for ADHD, predominantly inattentive type. We employed data from 148 children (M&nbsp;=&nbsp;8.7&nbsp;years), 58% male, and 57% Caucasian in a randomized clinical trial. Positive treatment response was defined as (a) 5 or fewer inattentive symptoms and (b) a decrease of at least 3 inattentive symptoms from baseline to posttreatment. Child HI, parental A/D, and child IQ were associated with positive response, as follows: Child HI had a main effect in which it was negatively associated with treatment response (36% with 2 or more HI symptoms were positive responders vs. 59% of those with 1 or no symptoms) that was qualified by parental A/D and child IQ. When children had 2 or more symptoms of HI and higher parental A/D, positive response rate was low at 25%; when children had 2 or more symptoms of HI, low parental A/D, and an IQ of 105 or higher, positive response rate was 85%. Furthermore, the group with the poorest response rate (25%) had parents who self-reported greater ADHD severity, and the group with a relatively good rate of positive response (59%) had the lowest number of oppositional defiant disorder symptoms. Likelihood of positive response to our behavioral treatment for ADHD-I is dependent on child and parent factors

Atomoxetine Improved Attention in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Dyslexia in a 16 Week, Acute, Randomized, Double-Blind Trial

Objective: The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept. Methods: Children and adolescents (10?16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0?1.4?mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale?Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C). Results: At week 16, atomoxetine treatment resulted in significant (p<0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores. Conclusions: Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT. Clinical Trials Registration: This study was registered at: http://clinicaltrials.gov/ct2/home, NCT00607919.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140320/1/cap.2013.0054.pd

Educational outcomes of a collaborative school–home behavioral intervention for ADHD.

This study evaluated educationally relevant outcomes from a newly developed collaborative school–home intervention (Collaborative Life Skills Program [CLS]) for youth with attention and/or behavior problems. Participants included 17 girls and 40 boys in second through fifth grades (mean age = 8.1 years) from diverse ethnic backgrounds. CLS was implemented by 10 school-based mental health professionals at their schools and included 3 integrated components over 12 weeks: group behavioral parent training, classroom behavioral intervention, and a child social and independence skills group. Parent and teacher ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms, organizational skills, and homework problems, and teacher-rated academic skills, report card grades, academic achievement, and classroom observations of student engagement were measured before and after treatment. Significant pre–post improvement was found for all measures, with large effect sizes for ADHD symptoms, organizational skills, and homework problems, and medium to large effects for teacher-rated academic skills, report card grades, academic achievement, and student engagement. Improvements in organizational skills mediated the relationship between improvement in ADHD symptoms and academic skills. Significant improvement in both ratings and objective measures (achievement testing, report cards, classroom observations) suggests that improvement exceeded what might be accounted for by expectancy or passage of time. Findings support the focus of CLS on both ADHD symptom reduction and organizational skill improvement and support the feasibility of a model which utilizes school-based mental health professionals as providers

Educational Outcomes of a Collaborative School–Home Behavioral Intervention for ADHD

This study evaluated educationally relevant outcomes from a newly developed collaborative school-home intervention (Collaborative Life Skills Program [CLS]) for youth with attention and/or behavior problems. Participants included 17 girls and 40 boys in second through fifth grades (mean age = 8.1 years) from diverse ethnic backgrounds. CLS was implemented by 10 school-based mental health professionals at their schools and included 3 integrated components over 12 weeks: group behavioral parent training, classroom behavioral intervention, and a child social and independence skills group. Parent and teacher ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms, organizational skills, and homework problems, and teacher-rated academic skills, report card grades, academic achievement, and classroom observations of student engagement were measured before and after treatment. Significant pre-post improvement was found for all measures, with large effect sizes for ADHD symptoms, organizational skills, and homework problems, and medium to large effects for teacher-rated academic skills, report card grades, academic achievement, and student engagement. Improvements in organizational skills mediated the relationship between improvement in ADHD symptoms and academic skills. Significant improvement in both ratings and objective measures (achievement testing, report cards, classroom observations) suggests that improvement exceeded what might be accounted for by expectancy or passage of time. Findings support the focus of CLS on both ADHD symptom reduction and organizational skill improvement and support the feasibility of a model which utilizes school-based mental health professionals as providers