ADHD: Overdiagnosed and overtreated, or misdiagnosed and mistreated?

In today's changing medical climate, physicians need to treat attention-deficit/hyperactivity disorder (ADHD) better and more cost-effectively. The authors review recommendations supported by recent research and offer simple practices that integrate medicine and behavioral health for patients with ADHD.

Development of an Objective Autism Risk Index Using Remote Eye Tracking.

OBJECTIVE: Abnormal eye gaze is a hallmark characteristic of autism spectrum disorder (ASD), and numerous studies have identified abnormal attention patterns in ASD. The primary aim of the present study was to create an objective, eye tracking-based autism risk index. METHOD: In initial and replication studies, children were recruited after referral for comprehensive multidisciplinary evaluation of ASD and subsequently grouped by clinical consensus diagnosis (ASD n = 25/15, non-ASD n = 20/19 for initial/replication samples). Remote eye tracking was blinded to diagnosis and included multiple stimuli. Dwell times were recorded to each a priori-defined region of interest (ROI) and averaged across ROIs to create an autism risk index. Receiver operating characteristic curve analyses examined classification accuracy. Correlations with clinical measures evaluated whether the autism risk index was associated with autism symptom severity independent of language ability. RESULTS: In both samples, the autism risk index had high diagnostic accuracy (area under the curve [AUC] = 0.91 and 0.85, 95% CIs = 0.81-0.98 and 0.71-0.96), was strongly associated with Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) severity scores (r = 0.58 and 0.59, p < .001), and not significantly correlated with language ability (r ≤| -0.28|, p > .095). CONCLUSION: The autism risk index may be a useful quantitative and objective measure of risk for autism in at-risk settings. Future research in larger samples is needed to cross-validate these findings. If validated and scaled for clinical use, this measure could inform clinical judgment regarding ASD diagnosis and track symptom improvements.

Evaluation of the Duration of Action and Comparative Effectiveness of Lisdexamfetamine Dimesylate and Behavioral Treatment in Youth With ADHD in a Quasi-Naturalistic Setting.

OBJECTIVE: This study compared the relative effects of three treatment conditions: long-acting stimulant medication (MED), behavior modification, and medication/behavioral treatments combined (COM) in children with ADHD. METHOD: A total of 25 children, aged 6 to 12 years, received the three treatment conditions during a 7-week Summer Treatment Program in an alternating treatments design. Counselors completed behavioral ratings from 0.5 to 12.5 hr post dose, and parents completed nighttime ratings. RESULTS: Ratings for SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) and for following instructions indicated COM and MED improved symptoms over BEH treatment beginning 3 hr post dose (p = .008), with ratings maintained 12.5 hr post dose (p = .001 and .006). Results for frustration tolerance indicated significant improvement in all three conditions until 9 hr post dose. CONCLUSION: MED and COM separated from BEH at 3 hr post dose, and sustained benefit was observed across the day for two of three measures. BEH appears to have an additive effect, extending the duration of frustration tolerance.

Psychosocial therapy in the treatment of adults with attention-deficit/hyperactivity disorder.

Optimal management of attention-deficit/hyperactivity disorder (ADHD) requires a comprehensive treatment approach that reduces symptoms and improves quality of life. Psychosocial therapy, an important adjunct to pharmacotherapy for patients with ADHD, enables patients to improve functional performance across domains of life and maximizes the benefits of symptom reduction achieved via medication. This article evaluates the main types of psychosocial therapies used in the treatment of adult ADHD and discusses treatment goals within the context of skill acquisition and strength optimization. Factors influencing the success of psychosocial therapy and the role of a comprehensive treatment approach are also examined. The sequenced presentation of symptom reduction and skill acquisition plays a key role in coordinating psychosocial therapy and pharmacotherapy in a multimodal strategy for the effective treatment of adult ADHD.

Changes in emotions related to medication used to treat ADHD. Part I: literature review.

OBJECTIVE: To summarize the literature investigating changes in emotional expression (EE) as a function of pharmacotherapy in the treatment of ADHD and to differentiate emotional effects related to ADHD pharmacotherapy from emotional effects related to ADHD as a disorder. METHOD: English language articles published from January 1, 1988, through August 31, 2008 were identified through a PubMed literature search using the search terms attention, ADHD, hyperactive, hyperkinesis, and ADD cross-referenced with medication terms amphetamine, lisdexamfetamine, methylphenidate , guanfacine, atomoxetine, and clonidine. The search was limited to randomized, controlled trials. Abstracts from all identified articles were selected for further review if they met criteria including (a) presence of a placebo arm, (b) children ≤ 18 years of age, (c) ≥ 20 participants, and (b) study design elements that would allow reviewers to determine whether EE phenomena were specifically attributable to medication effects versus alternative explanations (e.g., time, maturation, baseline comorbidity, selection artifacts, or treatments other than the medication-placebo contrast). Qualifying full-text articles were reviewed for prespecified EE terms. RESULTS: Of 148 articles that met selection criteria, 47 reported varying types of EE. Eight of these included two active treatment arms. Hence, 55 data sets were identified. Patterns of change in EE in studies meeting search criteria are discussed. Data sets that reported accounts of EE by the percentage of patients were compiled and further analyzed for specific medication classes. The changes in EE are further discussed as (a) salutary or detrimental, (b) associated with time of day or circumscribed, and (c) presumed to be caused by pharmacological effects. CONCLUSIONS: Definitive methodologies for assessing the presence of changes in EE in clinical trials and guidelines for the evaluation of EE in clinical practice are yet to be established and are needed. Such guidelines could be used by clinicians to monitor positive and negative changes in emotion when patients are taking medications for their ADHD.

Changes in emotions related to medication used to treat ADHD. Part II: clinical approaches.

ADHD is one of the most common neurobehavioral disorders of childhood, and FDA-approved medications offer an efficacious treatment option. However, case reports and anecdotal sources suggest that children can have emotional responses, both salutary and detrimental, to these agents. We have previously conducted a comprehensive literature review and found very few research studies systematically examining changes in emotional expression (EE) associated with ADHD medication use. In addition, no empirical data pertaining to the management of these responses could be found. Although few methodologically stringent data are available for changes in EE, such changes should be recognized and measured to determine appropriate responses by clinicians and to maximize treatment benefits and reduce side effects. In this companion report, we draw on available research evidence and clinical experience to explore typical clinical manifestations, differential diagnosis, scales for monitoring, and management approaches of EE observed with pharmacologic treatment of ADHD. In the future, controlled clinical trials of ADHD pharmacotherapy should employ standardized ratings of EE at baseline, during and after treatment. In addition, future research studies should examine various management approaches of these EE changes, to ensure maximal treatment benefits and minimal risks to patients with ADHD who are treated with medication.

Time course and predictors of health-related quality of life improvement and medication satisfaction in children diagnosed with attention-deficit/hyperactivity disorder treated with the methylphenidate transdermal system.

OBJECTIVE: The aim of this study was to evaluate the time course and predictors of improvement in health-related quality of life (HRQL) and medication satisfaction in children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and treated with the methylphenidate transdermal system (MTS). METHODS: Temporal relationships between ADHD symptoms, medication satisfaction, and HRQL measures were examined via latent growth curve, structural path, and growth mixture models. RESULTS: Higher levels of medication satisfaction at the end of titration predicted greater increases in family HRQL (p=0.004) and, to a lesser extent, child HRQL (p=0.068) throughout the study. At 4 of 6 (p<0.05) and 5 of 6 (p<0.10) contemporaneous time points, ADHD symptoms predicted child HRQL. At 2 of 6 (p<0.05) and 3 of 6 (p<0.10) contemporaneous time points, ADHD symptoms predicted family HRQL. ADHD did not predict child or family HRQL improvements at subsequent time points. A uniform pattern of change for child HRQL was noted, with most HRQL change following the pattern of symptom change during titration. Three distinct patterns of change were noted for family HRQL. CONCLUSIONS: In most cases, medication satisfaction, ADHD symptoms, and HRQL improved simultaneously, suggesting that HRQL was not a delayed response to improvement in symptoms. Children showed a uniform pattern of improvement in HRQL that followed symptom change; three distinct patterns of change were found for improvement in family HRQL.

Varying the wear time of the methylphenidate transdermal system in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Children with attention-deficit/hyperactivity disorder often have varying needs for coverage of their symptoms throughout the day. The objectives of this study were to determine the efficacy, duration of action, and safety of methylphenidate transdermal system worn for variable times by children (ages 6-12) diagnosed with ADHD. METHOD: Methylphenidate dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an Analog Classroom setting during a randomized, placebo-controlled, double-blind, three-way crossover phase. The main efficacy measures were the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and the Permanent Product Measure of Performance math test. RESULTS: All of the efficacy measures indicated that 4- and 6-hour wear times improved ADHD symptoms and that medication effects on the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and Permanent Product Measure of Performance math test decreased between 2 and 4 hours after patch removal. The majority of adverse events were transient and mild to moderate in severity. CONCLUSIONS: These findings suggest that the duration of medication effect is related to the wear time of the patch and may be tailored to accommodate the schedules of patients.

Pharmacologic treatment of ADHD: road conditions in driving patients to successful outcomes.

The names assigned to attention-deficit/hyperactive disorder (ADHD) have changed over the years. ADHD cannot be cured, and the patient with ADHD journeys through life with a burden. Although ADHD is most commonly studied in school-aged children, it is a syndrome that spans the life cycle, through adolescence and into adulthood. Improvements in patient adherence to pharmacologic treatment, attributable to the launch of new formulations, the availability of new non-schedule II drugs, and the development of novel drugs in late-stage clinical trials, are transforming the treatment of ADHD. For example, atomoxetine is a nonstimulant treatment, and lisdexamfetamine was developed with the goal of providing an extended duration of effect with a reduced potential for abuse, overdose toxicity, and drug tampering. Known adverse effects of stimulant treatment of ADHD include appetite suppression and sleep disturbance. Other adverse effects, such as growth suppression and substance use disorder, are controversial. The US Food and Drug Administration (FDA) recently issued a public health advisory for drugs approved for the treatment of ADHD to provide more information for patients about potential risks of ADHD medications. Additional research is needed on approaches for treating ADHD in adolescents transitioning into adulthood, as are studies on the relationships between ADHD and comorbidities such as substance use disorder.

Methylphenidate in the treatment of children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the short-term efficacy of methylphenidate in the treatment of youths with bipolar disorder (BD) and comorbid attention deficit/hyperactivity disorder (ADHD). METHOD: A 4-week double-blind, placebo-controlled trial in youths ages 5 to 17 years was conducted. Subjects met DSM-IV criteria for bipolar disorder and ADHD, were currently receiving a stable dose of at least one thymoleptic, and while euthymic continued to have clinically significant symptoms of ADHD. Patients received 1 week each of placebo, methylphenidate 5 mg twice daily, methylphenidate 10 mg twice daily, and methylphenidate 15 mg twice daily using a crossover design. Subjects were randomly assigned to receive one of six possible dosing orders. At study's end, and before the blind being broken, a "best dose week" for each subject was determined. The primary outcome measure was the total score on the parent-completed ADHD Rating Scale-IV. RESULTS: Sixteen patients, with a mean age of 10.43 (SD 3.14) years completed the trial. Lower scores during best dose treatment compared to the week of placebo treatment were found on the ADHD Rating Scale-IV (p < .05), suggesting a therapeutic benefit. A large effect size (Cohen's d = 0.90) was found for methylphenidate. Treatment was generally well tolerated. CONCLUSIONS: Euthymic youths with bipolar disorder and ADHD may benefit from short-term concomitant treatment with methylphenidate.

Developmental and subtype differences in behavioral assets and problems in children diagnosed with ADHD.

OBJECTIVE: Developmental and subtype differences in behavioral assets and problems were examined in 318 children newly diagnosed with ADHD. METHOD: Three age groups were compared: 4 to 6.9 years (n = 95), 7 to 9.9 years (n = 136), and 10 to 15 years (n = 87); with two subtypes examined: inattentive (n = 151), and hyperactive/combined (n = 167). Data on assets and problems were obtained from parental questionnaires. Analyses were conducted for the assets and problems data with subtype and age as between group factors. RESULTS: Younger children had more problems with hyperactivity, and the eldest group had more externalizing problems. The hyperactive/combined subtype exhibited more problems than the inattentive subtype. Also the younger group had more assets than the eldest group. CONCLUSION: Children who possessed greater assets had fewer behavioral problems, with assessment of assets and problems important in the diagnosis of ADHD.

Changes and challenges: managing ADHD in a fast-paced world.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing. Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP) provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement. OBJECTIVE: To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability, comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice. CONCLUSION: The pathophysiology of ADHD is linked to dysfunction of fronto-subcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture. Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulant agents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained-release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment outcomes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions.

A dose-ranging study of a methylphenidate transdermal system in children with ADHD.

OBJECTIVE: This was a multicenter, double-blind, randomized, dose-ranging study of a methylphenidate (MPH) transdermal system (MTS). Medication (placebo, 0.45, 0.9, and 1.8 mg/h) was crossed with application time (6 a.m., 7 a.m.) to evaluate MTS efficacy and influence of exposure time on morning effects. METHOD: The study took place in a summer treatment program (STP) at three sites, with 36 children aged 7-12 years with attention-deficit/hyperactivity disorder. Each treatment was administered for 1 day in random order, for a total of 8 days. Behavioral and academic measures were taken as well as patch wear characteristics and side effects. RESULTS: Evaluable participant data were analyzed in a series of dose x application time multivariate analyses of variance. All MTS conditions were significantly different from placebo across measures. Time of application had no significant effect on daily behavior, and effects of application time on morning behavior were inconclusive. Consistent with previous results in this setting, the highest dose produced limited incremental benefit compared with the mid-range dose. The wear characteristics of the MTS were acceptable, and the formulation was well tolerated. CONCLUSIONS: The MTS produced significant effects that were similar to those previously reported with comparable MPH doses. There does not appear to be a substantial effect of application time on total daily functioning in this setting; further controlled time-course studies will be necessary to evaluate the question of morning onset fully.

A prospective study of stimulant response in preschool children: insights from ROC analyses.

OBJECTIVE: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. METHOD: Twenty-eight preschoolers (ages 4.0 - 5.9) participated in the present investigation. They were obtained consecutively from a large sample of suburban children assessed for attention-deficit/hyperactivity disorder. After having received various dosing levels of a stimulant in a placebo-controlled crossover design, best dose was assigned based on the lowest Abbreviated Symptoms Questionnaire T score received in a given week. All analyses compared best dose ratings to placebo ratings. RESULTS: Preschoolers' behavioral ratings by parents and teachers were improved as a function of stimulant medication. More than 82% of the medicated sample improved their behavioral rating by at least 1 SD as demonstrated by receiver operating characteristic (ROC) analyses, with more than 50% of medicated preschoolers improving by more than 2 SD. Side effects were infrequent at best dose of medication. CONCLUSIONS: Clinically significant changes in behavioral ratings of preschoolers were noted in response to stimulant medication. Both stimulants were well tolerated. ROC curves were useful for clearly depicting on a case-by-case basis how much improvement was derived from psychopharmacological treatment.

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study.

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with attention deficit hyperactivity disorder (ADHD). Recently, several studies have documented the efficacy of a new stimulant, Adderall. Although these initial studies provide useful information for clinicians treating ADHD children, their method of data presentation has provided limited information about the clinical significance of drug effects. Thus, to address the issue of clinical significance, we completed drug-placebo response curve analyses of a blinded, placebo-controlled study of Adderall and methylphenidate (MPH). Our results show that the efficacy of Adderall and MPH to improve functioning is seen throughout the full range of improvement scores. Both drugs prevent worsening and, for a majority of patients, lead to improvements that are well into the normal range. The analyses also highlight an important subgroup of placebo responders, which suggests that future research should focus on how to predict robust placebo response in ADHD patients.