Medication refusal in children with oppositional defiant disorder or conduct disorder and comorbid attention-deficit/hyperactivity disorder: medication history and clinical correlates

Abstract Objective: This study examines the characteristics of 96 children with attention-deficit/hyperactivity disorder (ADHD) and their families who refused a recommendation for medication as part of their treatment for disruptive disorders. Methods: The ADHD cases were taken from a sample of 139 youth (age 6-11) who were recruited for a clinical trial that compared the administration of a modular psychosocial treatment in an outpatient clinic or community settings. Medication management was an optional treatment module for children with ADHD in both conditions. Children who were (vs. were not) taking medication at intake, and children who accepted (vs. refused) medication recommendations during the study were compared on diagnostic and clinical measures related to child, school, parent, and family domains of functioning. Results: Parents of 30% of the children refused study medication for ADHD. Parental medication acceptability and intake correlated highly with both medication history and study refusal of medication. Increased parental self-efficacy and emotional support for their youth correlated with medication refusal. No demographics and few child or school factors were associated with medication refusal. Medication use was associated with reductions in some key ADHD symptoms, but did not affect disruptive behaviors as did the psychosocial interventions. Conclusion: Medication refusers remain poorly understood but certain correlates, such as parental self-efficacy, parental emotional support for their youth, and medication acceptability, warrant further evaluation.     

Methylphenidate response in aggressive and nonaggressive ADHD children: distinctions on laboratory measures of symptoms.

Response to a single, 5-mg dose of methylphenidate was compared in aggressive and nonaggressive attention-deficit hyperactivity disorder (ADHD) children using objective measures of inattention, impulsivity, and activity level. After medication, both ADHD groups had a significant decrease in inattention, whereas impulsivity remained unchanged. Activity level decreased only in the nonaggressive ADHD group. Unmedicated normal controls showed no change on any measure. These results support the hypothesis that aggressive and nonaggressive ADHD children have somewhat different underlying determinants for some of their symptoms. In addition, they suggest that inattention, impulsivity, and overactivity may be mediated by partially distinct neural mechanisms.     

The Utility of Home Problem Pervasiveness and Severity in Classifying Children Identified with Attention-Deficit/Hyperactivity Disorder

Given the propensity for clinical assessment of Attention-Deficit/Hyperactivity Disorder (ADHD) to focus on core behavioral symptoms, the current study examined how well other predictors classified children who were diagnosed with ADHD by licensed practitioners. Participants were 91 children (39 ADHD-identified, 52 without ADHD), aged 8 to 13 years. In addition to significantly more ADHD symptoms, the ADHD-identified group exhibited significantly more externalizing problems and internalizing symptoms, less adaptive functioning, and greater problem pervasiveness and severity. Binary logistic regression analyses indicated that problem pervasiveness and severity significantly predicted diagnostic group membership when controlling for other predictors, and pervasiveness added unique variance beyond measures of core ADHD symptoms. Diagnostic utility analyses showed measurement of problem pervasiveness and severity to be a useful tool in the identification of ADHD. Findings provide support for the practical use of a parent-report measure of impairment in the home as part of evidence-based assessment of ADHD.     

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.     

Noninvasive brain stimulation in children and adults with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis

BackgroundRepetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) could provide treatment alternatives to stimulant medication for attention-deficit/hyperactivity disorder (ADHD), given some evidence for improvements in cognition and clinical symptoms. However, despite a lack of solid evidence for their use, rTMS and tDCS are already offered clinically and commercially in ADHD. This systematic review and meta-analysis aimed to critically appraise rTMS and tDCS studies in ADHD to inform good research and clinical practice.MethodsA systematic search (up to February 2019) identified 18 studies (rTMS 4, tDCS 14; 311 children and adults with ADHD) stimulating mainly the dorsolateral prefrontal cortex (dlPFC). We included 12 anodal tDCS studies (232 children and adults with ADHD) in 3 random-effects meta-analyses of cognitive measures of attention, inhibition and processing speed.ResultsThe review of rTMS and tDCS showed positive effects in some functions but not others, and little evidence for clinical improvement. The meta-analyses of 1 to 5 sessions of anodal tDCS over mainly the left or bilateral dlPFC showed trend-level improvements in inhibition and processing speed, but not in attention.LimitationsHeterogeneity in stimulation parameters, patient age and outcome measures limited the interpretation of findings.ConclusionThe review and meta-analysis showed limited evidence that 1 to 5 sessions of rTMS and tDCS, mostly of the dlPFC, improved clinical or cognitive measures of ADHD. These findings did not support using rTMS or tDCS of the dlPFC as an alternative neurotherapy for ADHD as yet. Larger, multi-session stimulation studies identifying more optimal sites and stimulation parameters in combination with cognitive training could achieve larger effects.     

Ten-year review of rating scales. V: scales assessing attention-deficit/hyperactivity disorder

OBJECTIVE: This article summarizes information on scales assessing attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHOD: The authors sampled articles on ADHD over the past decade. Several popular older ADHD measures have recently been revised, and new ADHD scales have been developed. The authors selected primarily ADHD scales based on the DSM-IV construct of ADHD that also have multiple literature citations. They then reviewed their psychometric properties. Those with adequate psychometric functioning plus considerable literature citations, known wide usage in clinical practice, or a current niche are presented here. RESULTS: Several rating scales consistent with the DSM-IV conceptualization of ADHD are now available for use in both home and school settings. Many of the instruments demonstrate solid psychometric properties and a strong normative base. However, some popular scales have not been adequately investigated. Some measures are restricted to the comprehensive assessment of ADHD, whereas others also include symptoms of other disorders. The potential applications for these scales with youths diagnosed with ADHD are broad. CONCLUSIONS: Rating scales can reliably, validly, and efficiently measure DSM-IV-based ADHD symptoms in youths. They have great utility in research and clinical work, assist treatment planning, and help to ensure accountability in practice.     

Rate dependency revisited: understanding the effects of methylphenidate in children with attention deficit hyperactivity disorder

Although stimulants are widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), their calming effects are not easily understood. One hypothesis derived from preclinical studies is that stimulants exert "rate-dependent" effects that are inversely related in magnitude and direction to the baseline rate of activity or distraction. Previously, compelling support for this hypothesis has been lacking. We provide preliminary evidence that methylphenidate exerts rate-dependent behavioral effects in children with ADHD. Activity and attention were quantified in children with ADHD tested on placebo and different doses of methylphenidate using objective measures. Higher doses altered activity and attentiveness in a rate-dependent manner after correction for regression-to-the-mean artifacts. These findings illustrate a clear inverse association between symptom severity and degree of therapeutic response that is crucial for our understanding of stimulant effects and effective clinical treatment of ADHD.     

Evaluation of Screening in Children Referred for an ADHD Assessment

Although guidance from the National Institute for Clinical Excellence recommends the improved identification of children with ADHD, clinical resources are limited. Amongst children (n = 119) referred over the question of ADHD, we evaluated the utility of screening (using parent and teacher questionnaires) prior to offering an ADHD assessment. The introduction of screening contributed to an increase in the proportion of assessed children receiving a clinical diagnosis of ADHD. Although screening of referred children prior to assessment can optimise the use of specialist clinical resources in the identification of children with ADHD, false positives remain common.     

Does actigraphy differentiate ADHD subtypes in a clinical research setting?

OBJECTIVE: To compare subtypes of attention-deficit/hyperactivity disorder (ADHD) (predominantly inattentive and combined types) and a comparison group on an objective measure of activity level (actigraphy). METHOD: Actigraphs were worn by 64 children (49 boys, 15 girls) during a full-day clinical diagnostic assessment; 20 subjects had a diagnosis of ADHD predominantly inattentive type, 22 had ADHD combined type, and 22 were non-ADHD controls. Mean actigraph scores were calculated for two 2-hour intervals, comprising, respectively, a psychometric evaluation in the morning and the completion of a speech and language assessment and research measures in the afternoon. RESULTS: There were no significant group differences in activity level in the morning session. During the afternoon session, children with ADHD were significantly more active than controls, but there were no differences between ADHD subtypes. CONCLUSIONS: These data partially support specifications in the DSM-IV regarding hyperactivity in ADHD; however, they also indicate that situational and/or temporal factors may affect the degree to which hyperactivity is expressed. Furthermore, the findings contradict specifications in the DSM-IV that suggest that children with ADHD combined type should be more hyperactive than children with ADHD predominantly inattentive type.     

ADHD subtypes are associated differently with circadian rhythms of motor activity,sleep disturbances,and body mass index in children and adolescents: a case–control study

To date, few studies have examined the circadian pattern of motor activity in children and adolescents newly diagnosed with attention-deficit/hyperactivity disorder (ADHD). The objective was to study the circadian pattern of motor activity in subjects with ADHD (medication naïve) and to investigate the relationships between alterations in circadian patterns, the ADHD subtype (combined or inattentive), sleep disturbances and body mass index (BMI). One-hundred twenty children and adolescents (60 medication naïve ADHD and 60 controls) were included in a gender- and age-matched case–control study. ADHD was diagnosed according to the DSM-IV-TR, the Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, and the Conner’s Parents Rating Scale-Revised. Circadian rhythms of motor activity and sleep parameters were measured using actigraphy and the Sleep Disturbance Scale for Children. BMI and dietary intake were also evaluated. ADHD patients showed a trend towards eveningness and greater sleep disturbances than controls. Additionally, patients with ADHD-combined had significantly higher mean values of motor activity and showed a significant delay in bedtime. Furthermore, among ADHD-C patients hyperactivity symptoms were significantly associated with the least 5 h of activity. Regarding patients with ADHD-inattentive, increased fragmentation of the circadian pattern was associated with inattention symptoms, and they also showed a significant increase in BMI of 2.52 kg/m² [95% CI 0.31, 4.73] in comparison with controls. Our findings highlight the potential use of actigraphy as a clinical tool to aid in the diagnosis of ADHD. It should be noted that evaluating motor activity variables could also allow the differentiation between ADHD subtypes.

     

Improving psychostimulant adherence in children with ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder of childhood, characterized by excessive inattention, hyperactivity and impulsivity. Effective medication exists for the condition, yet suboptimal long-term effects persist for children with ADHD. Poor adherence is a common issue for individuals with chronic conditions, including children and those with psychiatric conditions, and ADHD is no exception. This review examines the available evidence regarding patterns of long-term use of stimulant medication and the predictors of medication discontinuation among children with ADHD, and suggests future clinical and research directions for improving adherence in children with ADHD.     

Objective measures of activity and attention in the differential diagnosis of psychiatric disorders of childhood

Objective measures of attention, concentration, and motor activity can be used effectively in the assessment and differential diagnosis of bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) in children. Children with BD were evaluated using actigraphy and the McLean Motion Analysis Test (M-MAT), and the results were compared with age- and gender-matched ADHD and normative data. Actigraphy indicated decreased sleep efficiency and duration with BD, with a longer latency and increased nocturnal activity. Using M-MAT clinicians were able to detect cognitive impairment and activation in children with mania, and worse-than-normal scores on measures of attention and increased levels of activity and impulsiveness in children with BD. Thus, objective measures of attention and activity can be of assistance in the differential diagnosis of ADHD and BD.     

Assessing ADHD symptoms in children and adults: evaluating the role of objective measures

Background

Diagnostic guidelines recommend using a variety of methods to assess and diagnose ADHD. Applying subjective measures always incorporates risks such as informant biases or large differences between ratings obtained from diverse sources. Furthermore, it has been demonstrated that ratings and tests seem to assess somewhat different constructs. The use of objective measures might thus yield valuable information for diagnosing ADHD. This study aims at evaluating the role of objective measures when trying to distinguish between individuals with ADHD and controls. Our sample consisted of children (n?=?60) and adults (n?=?76) diagnosed with ADHD and matched controls who completed self- and observer ratings as well as objective tasks. Diagnosis was primarily based on clinical interviews. A popular pattern recognition approach, support vector machines, was used to predict the diagnosis.

Results

We observed relatively high accuracy of 79% (adults) and 78% (children) applying solely objective measures. Predicting an ADHD diagnosis using both subjective and objective measures exceeded the accuracy of objective measures for both adults (89.5%) and children (86.7%), with the subjective variables proving to be the most relevant.

Conclusions

We argue that objective measures are more robust against rater bias and errors inherent in subjective measures and may be more replicable. Considering the high accuracy of objective measures only, we found in our study, we think that they should be incorporated in diagnostic procedures for assessing ADHD.

     

Non-stimulant treatments for ADHD

We reviewed the literature of medication trials in ADHD to evaluate the scope of the available non-stimulant treatments. A variety of compounds with a common noradrenergic/ dopaminergic activity have shown documented anti-ADHD activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. In addition, the atypical antidepressant bupropion and the novel noradrenergic specific antidepressant tomoxetine have also been documented to be effective in the treatment of ADHD in controlled clinical trials. Despite wide use, the scientific base supporting the efficacy of alpha-2, noradrenergic agonists continues to be limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhancing drugs in such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacologic treatments for the treatment of ADHD.

     

Sleep problems in children with autism, attention-deficit hyperactivity disorder, and epilepsy

This study aimed to examine sleep problems in children with autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), and epilepsy in clinical settings. We assessed 64 children with ASD, 64 with ADHD, 64 with epilepsy, and 64 typically developing children without any neuropsychiatric disorders by using a sex-and age-matched case-control study design. The parents reported their children's sleep problems. Parents of children with ASD and ADHD reported more current and lifetime sleep problems of their children than parents of children with epilepsy, especially in snoring and restless legs syndrome. Current or lifetime sleep problems did not differ between children with ASD and children with ADHD, or between children with epilepsy and typically developing children. Demographic characteristics and medication status could not fully explain the increased risk of sleep problems in children with ASD and ADHD. Our findings lend evidence to support more sleep problems in children with ASD and ADHD than typically developing children. Our study adds that children with epilepsy do not. These findings emphasize the importance to assess sleep problems in children with neurodevelopmental disorders highly comorbid with ASD or ADHD in clinical practice.     

Methylphenidate in children with oppositional defiant disorder and both comorbid chronic multiple tic disorder and ADHD

Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder.     

Sources of auditory selective attention and the effects of methylphenidate in children with attention-deficit/hyperactivity disorder.

BACKGROUND: The aim of this study was to determine 1) whether abnormal auditory selective attention in children with attention-deficit/hyperactivity disorder (ADHD), as reflected in the processing negativity (PN) of the event-related potential, is related to impaired frontal functioning; and 2) how methylphenidate (MPh) affects attentional functioning in ADHD. METHODS: Sources of electrical brain activity were estimated in healthy control children, in ADHD children without medication, and in children with ADHD during a placebo-controlled medication trial involving MPh. RESULTS: The source models showed that the PN is generated in the auditory cortex. Children with ADHD showed less activity related to selective attention in this brain region. Administration of MPh resulted in more frontally located sources. CONCLUSIONS: The results showed no evidence for an important role of the frontal cortex in abnormalities in selective attention in children with ADHD. Also, the data did not indicate that MPh normalizes brain activity in these children.     

Stimulant medication effects in a summer treatment program among young children with attention-deficit/hyperactivity disorder

OBJECTIVE: This study examined the effectiveness of stimulant medication on multiple domains of functioning in 36 young (5 to 6 years old) children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: Five- and 6-year-old children attending a summer treatment program between 1987 and 1997 underwent a randomized clinical assessment of the effect of two doses of methylphenidate (0.3 mg/kg versus 0.6 mg/kg) and placebo on social behavior and academic performance. RESULTS: Methylphenidate had an effect on all four social behaviors and improved two of the three areas of academic functioning. Dose effects were present for three of the seven dependent measures. Individual analyses indicated a therapeutic response rate between 39% and 100% across dependent measures. Furthermore, individual analyses of response indicated that across several important dependent measures, 39% to 98% of children showed little incremental improvement with the higher dose compared with the lower dose of stimulant medication. CONCLUSIONS: Stimulant medication is an effective treatment for young children diagnosed with ADHD; however, multiple domains of functioning must be assessed to determine the most effective dose for young children with ADHD.     

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.