Atomoxetine, Parent Training, and Their Combination in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Impairments associated with attention-deficit/hyperactivity disorder (ADHD) and noncompliance are prevalent in children with autism spectrum disorder (ASD). However, ADHD response to stimulants is well below rates in typically developing children, with frequent side effects. Group studies of treatments for noncompliance are rare in ASD. We examined individual and combined-effectiveness of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance. METHOD: In a 3-site, 10-week, double-blind, 2 × 2 trial of ATX and PT, 128 children (ages 5-14 years) with ASD and ADHD symptoms were randomized to ATX, ATX+PT, placebo+PT, or placebo. ATX was adjusted to optimal dose (capped at 1.8 mg/kg/day) over 6 weeks and maintained for 4 additional weeks. Nine PT sessions were provided. Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson, Nolan and Pelham (SNAP) scale and Home Situations Questionnaire (HSQ). RESULTS: On the SNAP, ATX, ATX+PT and placebo+PT were each superior to placebo (effect sizes 0.57-0.98; p values of .0005, .0004, and .025, respectively). For noncompliance, ATX and ATX+PT were superior to placebo (effect sizes 0.47-0.64; p values .03 and .0028, respectively). ATX was associated with decreased appetite but was otherwise well tolerated. CONCLUSION: Both ATX and PT resulted in significant improvement on ADHD symptoms, whereas ATX (both alone and combined with PT) was associated with significant decreases on measures of noncompliance. ATX appears to have a better side effects profile than psychostimulants in the population with ASD. CLINICAL TRIAL REGISTRATION INFORMATION: Atomoxetine, Placebo and Parent Management Training in Autism; http://clinicaltrials.gov/; NCT00844753.

Comorbid anxiety and social avoidance in treatment of severe childhood aggression: response to adding risperidone to stimulant and parent training; mediation of disruptive symptom response.

OBJECTIVE: In the four-site Treatment of Severe Childhood Aggression (TOSCA) study, addition of risperidone to stimulant and parent training moderately improved parent-rated disruptive behavior disorder (DBD) symptoms. This secondary study explores outcomes other than DBD and attention-deficit/hyperactivity disorder (ADHD) as measured by the Child and Adolescent Symptom Inventory-4R (CASI-4R). METHODS: A total of 168 children ages 6-12 with severe aggression (physical harm), DBD, and ADHD were randomized to parent training plus stimulant plus placebo (basic treatment) or parent training plus stimulant plus risperidone (augmented treatment) for 9 weeks. All received only parent training plus stimulant for the first 3 weeks, then those with room for improvement received a second drug (placebo or risperidone) for 6 weeks. CASI-4R category item means at baseline and week 9 were entered into linear mixed-effects models for repeated measures to evaluate group differences in changes. Mediation of the primary DBD outcome was explored. RESULTS: Parent ratings were nonsignificant with small/negligible effects, but teacher ratings (n=46 with complete data) showed significant augmented treatment advantage for symptoms of anxiety (p=0.013, d=0.71), schizophrenia spectrum (p=0.017, d=0.45), and impairment in these domains (p=0.02, d=0.26), all remaining significant after false discovery rate correction for multiple tests. Improvement in teacher-rated anxiety significantly (p=0.001) mediated the effect of risperidone augmentation on the primary outcome, the Disruptive-total of the parent-rated Nisonger Child Behavior Rating Form. CONCLUSIONS: Addition of risperidone to parent training plus stimulant improves not only parent-rated DBD as previously reported, but also teacher-rated anxiety-social avoidance. Improvement in anxiety mediates improvement in DBD, suggesting anxiety-driven fight-or-flight disruptive behavior with aggression, with implications for potential treatment strategies. Clinicians should attend to possible anxiety in children presenting with aggression and DBD. CLINICAL TRIAL REGISTRY: Treatment of Severe Childhood Aggression (The TOSCA Study). NCT00796302. clinicaltrials.gov.

An integrated dietary/nutritional approach to ADHD.

Dietary and herbal interventions for attention-deficit/hyperactivity disorder (ADHD) have been proposed by practitioners of Western medicine and traditional Chinese medicine. Children who are suspected to have nutritional deficiencies, insufficiencies, and/or food allergies should be evaluated and, if the suspicion is confirmed, treated with supplementation or specific food elimination as part of standard care. Limited research exists on the efficacy and safety of dietary intervention as an adjunct to conventional medication; thus, improvement and side effects should be closely monitored.

Risperidone added to parent training and stimulant medication: effects on attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression.

OBJECTIVE: In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication, and placebo (Basic therapy) versus parent training, stimulant, and risperidone (Augmented therapy) by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced impairment, and informant discrepancy. METHOD: Children (6-12 years of age; N = 168) with severe physical aggression, ADHD, and co-occurring ODD/CD received an open trial of parent training and stimulant medication for 3 weeks. Participants failing to show optimal clinical response were randomly assigned to Basic or Augmented therapy for an additional 6 weeks. RESULTS: Compared with Basic therapy, children receiving Augmented therapy experienced greater reduction in parent-rated ODD severity (p = .002, Cohen's d = 0.27) and peer aggression (p = .02, Cohen's d = 0.32) but not ADHD or CD symptoms. Fewer children receiving Augmented (16%) than Basic (40%) therapy were rated by their parents as impaired by ODD symptoms at week 9/endpoint (p = .008). Teacher ratings indicated greater reduction in ADHD severity (p = .02, Cohen's d = 0.61) with Augmented therapy, but not for ODD or CD symptoms or peer aggression. Although both interventions were associated with marked symptom reduction, a relatively large percentage of children were rated as impaired for at least 1 targeted disorder at week 9/endpoint by parents (Basic 47%; Augmented 27%) and teachers (Basic 48%; Augmented 38%). CONCLUSION: Augmented therapy was superior to Basic therapy in reducing severity of ADHD and ODD symptoms, peer aggression, and symptom-induced impairment, but clinical improvement was generally context specific, and effect sizes ranged from small to moderate. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrials.gov/; NCT00796302.

What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder?

OBJECTIVE: Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested. METHOD: One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n = 84) or PT, STIM, and risperidone (Augmented treatment; n = 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n = 124) or conduct disorder (n = 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale. RESULTS: Compared with Basic treatment (PT + STIM [44.8 ± 14.6 mg/day] + placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT + STIM [46.1 ± 16.8 mg/day] + risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement on the Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p = .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p = .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p = .01). Clinical Global Impressions scores were substantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score ≤2, 70% for Basic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor. CONCLUSIONS: Risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behaviors when added to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: http://clinicaltrials.gov, unique identifier: NCT00796302.

Dietary and nutritional treatments for attention-deficit/hyperactivity disorder: current research support and recommendations for practitioners.

Evidence for dietary/nutritional treatments of attention-deficit/hyperactivity disorder (ADHD) varies widely, from double-blind, placebo-controlled trials to anecdotal. In guiding patients, clinicians can apply the SECS versus RUDE rule: treatments that are Safe, Easy, Cheap, and Sensible (SECS) require less evidence than those that are Risky, Unrealistic, Difficult, or Expensive (RUDE). Two nutritional treatments appear worth general consideration: Recommended Daily Allowance/Reference Daily Intake multivitamin/mineral supplements as a pediatric health intervention not specific to ADHD and essential fatty acids, especially a mix of eicosapentaenoic acid, docosahexaenoic acid, and γ-linolenic acid as an ADHD-specific intervention. Controlled studies support the elimination of artificial food dyes to reduce ADHD symptoms, but this treatment may be more applicable to the general pediatric population than to children with diagnosed ADHD. Mineral supplementation is indicated for those with documented deficiencies but is not supported for others with ADHD. Carnitine may have a role for inattention, but the evidence is limited. Dimethylaminoethanol probably has a small effect. Herbs, although "natural," are actually crude drugs, which along with homeopathic treatments have little evidence of efficacy. Consequences of delayed proven treatments need consideration in the risk-benefit assessment of dietary/nutritional treatments.

Cognitive deficits and positively biased self-perceptions in children with ADHD.

This study examined the relation between cognitive deficits and positive bias in a sample of 272 children with and without Attention Deficit Hyperactivity Disorder (ADHD; 7-12 years old). Results indicated that children with ADHD with and without biased self-perceptions exhibit differences in specific cognitive deficits (executive processes, working memory, broad attention, and cognitive fluency) compared to each other and to control children. Further, specific cognitive deficits emerged as partial mediators of the relation between ADHD diagnostic status and positive bias. Interestingly, some differences in results emerged based on the domain considered (academic, social, behavioral competence). Results lend initial support to the role of cognitive deficits in the positive bias of some children with ADHD. Implications for future research and intervention are discussed.

Multimodal treatment for childhood attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood disorders, characterized by developmentally inappropriate levels of inattention and/or hyperactivity/impulsivity. These core symptoms lead to impairment in home, school and peer contexts. Evidence-based treatments for ADHD include medication management (generally with stimulant medications), behavioral interventions (such as behavioral parent training, school consultation, and direct contingency management), or the combination of pharmacological and behavioral approaches. This review outlines each of these treatment strategies, reviews the rationale and evidence base currently existing for the use of multimodal rather than unimodal treatments (i.e., medication or behavioral intervention alone), and discusses potential moderators of multimodal treatment efficacy, as well as future directions for research, that may better inform clinical practice.

Parenting, family loneliness, and peer functioning in boys with attention-deficit/hyperactivity disorder.

The goal of the present study was to consider the associations between family functioning (parenting and family loneliness) and peer functioning in a sample of boys with ADHD (N = 110) and their mothers (N = 108) and fathers (N = 53). Results indicated that higher paternal warmth was associated with more peer acceptance, less peer rejection, and less problematic social behavior, but only for boys who reported low levels of family loneliness. In addition, more paternal power assertion was related to less peer acceptance, but only for boys who reported low levels of family loneliness. Maternal warmth and power assertion were not significantly related to boys' peer functioning. We discuss these findings in the context of the processes by which parenting may affect the peer relationships of these children.