Michael J. Manos

Short-Term Cardiovascular Effects of Methylphenidate and Adderall

OBJECTIVE The primary purpose of this study was to examine the cardiovascular effects of Adderall (ADL) in a clinic-based group of youths with attention-deficit/hyperactivity disorder ranging in age from 4 to 17 years. METHOD One hundred thirty-seven patients were treated with either methylphenidate (MPH) or ADL. Youths prescribed MPH were given medication twice daily, and youths treated with ADL received medication once daily. Patients were evaluated under five conditions: baseline, placebo, 5 mg/dose, 10 mg/dose, or 15 mg/dose. Resting pulse, diastolic blood pressure, and systolic blood pressure were examined after 1 week at each treatment condition. Changes from baseline on these parameters were examined. RESULTS The short-term cardiovascular effects of both ADL and MPH were modest. No patients experienced any clinically significant change in these cardiovascular measures during the course of this brief trial. CONCLUSION Since the short-term cardiovascular effects of ADL appear minimal, specific cardiovascular monitoring during short-term ADL treatment at doses of 15 mg/day or less does not appear to be indicated. In addition, under similar conditions, using similar methods, both medication treatments led to changes in blood pressure and pulse that were clinically insignificant.

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.

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.

HRQL and medication satisfaction in children with ADHD treated with the methylphenidate transdermal system.

Abstract Objective: To evaluate the impact of methylphenidate transdermal system (MTS) on health-related quality of life (HRQL) and medication satisfaction in children with attention-deficit/hyperactivity disorder (ADHD) as well as to identify potential moderators of HRQL and medication satisfaction. Research design and methods: Children aged 6–12 years diagnosed with ADHD were enrolled (N = 128) and 115 children completed the study. MTS 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 in a randomized, placebo-controlled, double-blind, three-way crossover design study. Main outcome measures: The ADHD Impact Module-Children (AIM-C), a validated HRQL instrument, was used to assess the impact of ADHD symptoms on children and their families. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS). A parent or legally appointed representative (LAR) completed the measures. Tolerability was monitored by spontaneous adverse event reporting. Results: Mean scores on AIM-C child and family HRQL scales improved from baseline to endpoint across all MTS doses and the magnitude of improvement increased with time from baseline. Improvement was noted for behavior, missed doses, worry, and economic impact AIM-C scores. Overall, parents/LARs indicated a high level of satisfaction with their childs use of MTS (Visit 7 [92.1%]; Visit 10 [89.1%]). Most treatment-emergent adverse events (TEAEs) were mild to moderate. The most frequent TEAEs included decreased appetite (28%), headache (21%), insomnia (20%), and abdominal pain (12%). Conclusions: At study endpoint, MTS treatment of ADHD was associated with robust improvement in child and family HRQL, key economic impact items, and overall medication satisfaction with the effectiveness and ease of use of MTS as an ADHD treatment. Also, the majority of MTS TEAEs were mild to moderate in severity. Limitations of this study included the potential for a significant halo effect when measuring HRQL and medication satisfaction as well as the uncertainty regarding whether the improvements seen over this relatively short study duration would be sustainable long term. Clinical trial registration: #NCT00151970.

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. (J. of Att. Dis. 2011; 15(2) 101-112)

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.

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. (J. of Att. Dis. 2007; 11(1) 28-36)

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. (J. of Att. Dis. 2011; 15(2) 113-121)

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.

Elementary and Middle School Teachers' Self-Reported Use of Positive Behavioral Supports for Children with ADHD: A National Survey.

This study examined elementary and middle school teachers’ self-reported use of behavioral supports for students with attention-deficit/hyperactivity disorder (ADHD) from a national sample of teachers. This information is important given increased attention and emphasis on universal and targeted strategies within problem-solving models in schools. Participants were teachers surveyed from 26 states across North America about their use of behavioral supports for their students with ADHD. Results are grouped by primary (K–2), intermediate (3–5), and middle (6–8) school levels. Results from this survey demonstrate that teachers report using significantly more universal and targeted strategies in the primary and intermediate school levels than teachers in the middle school level, revealing a reduction of behavioral supports for students with ADHD as they move into the middle school years. These findings have have implications for targeting school-based interventions for students with ADHD as they transition into middle school.