Efficacy of two long-acting methylphenidate formulations in children with attention- deficit/hyperactivity disorder in a laboratory classroom setting

OBJECTIVE: The aim of this study was to compare efficacy and safety of two long-acting formulations of methylphenidate (MPH) for attention-deficit/hyperactivity disorder (ADHD) in school-age children. METHODS: Children 6-12 years of age diagnosed with ADHD and stabilized on MPH (20-40 mg/day) participated in a five-way, randomized, placebo-controlled, single-blind, crossover study conducted in a laboratory classroom setting. Children alternately received single doses of extended-release MPH (ER-MPH) 20 and 40 mg, modified-release MPH (OROS-MPH) 18 and 36 mg, and placebo over 6 consecutive weeks. Efficacy was assessed using SKAMP rating subscales and written math tests. Data were examined using between-treatment comparisons of area under the curve (AUC) for change from predose values during hours 0-4, 0-8, 8-12, and 0-12. Safety was assessed. RESULTS: Fifty-three children completed the study. For all efficacy measures, improvements from predose were significantly greater with ER-MPH 40 mg than with OROS-MPH 36 mg in terms of AUC(0-4) (p < or = 0.005), AUC(0-8) (p < or = 0.006), and AUC(0-12) (p < or = 0.035). For most measures, ER-MPH 20 mg was equivalent to both doses of OROS-MPH in AUC(0-4), AUC(0-8), and AUC(0-12). No serious adverse events were reported. CONCLUSIONS: The efficacy of ER-MPH 20 mg is similar to that of OROS-MPH 18 and 36 mg during the first 8 hours postdose. Statistically greater benefits are observed with ER-MPH 40 mg than with OROS-MPH 36 mg and persist through hour 8. Active treatments show comparable efficacy from 8 to 12 hours postdose. Both doses of each MPH formulation are well tolerated.     

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.     

Effect of methylphenidate on Stroop Color-Word task performance in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome common in the pediatric population. It is associated with multiple nonspecific deficits on neuropsychological tests of executive function, and a beneficial response to pharmacotherapy with methylphenidate (MPH) and other psychostimulants. The Stroop Color-Word task is used empirically as an aid in diagnosis and treatment monitoring of ADHD; however, data on the sensitivity of the Stroop interference score to the effects of MPH are limited. To address this issue, we studied Stroop performance in a cohort of 18 MPH-treated prepubescent boys with ADHD and six healthy controls on and off MPH treatment conditions. MPH significantly improved performance in both groups, with the ADHD participants consistently displaying worse scores than those of controls both on and off MPH. These results suggest that though the diagnostic value of the Stroop task in ADHD remains controversial, it has heuristic value for monitoring clinical responses to MPH treatment. More research is needed to ascertain the clinical significance of our findings and to replicate this relatively small effect in a larger cohort, to determine whether MPH effects on Stroop performance are specific to ADHD symptoms or they generalize to other forms of symptomatology.     

Effect of transdermal methylphenidate wear times on sleep in children with attention deficit hyperactivity disorder

Sleep disturbances are common among children and adolescents with attention deficit hyperactivity disorder. This study sought to evaluate the effects of individualizing wear times of the methylphenidate transdermal system on sleep parameters. In this open-label, randomized trial, 26 children with attention deficit hyperactivity disorder and sleep disturbances were randomized (after dose optimization) to one of four groups with different sequences of patch wear times (i.e., 9, 10, 11, and 12 hours per day wear times each for week in different sequences). The primary endpoint comprised sleep latency. Secondary endpoints included total sleep time, sleep quality, and attention deficit hyperactivity disorder and related signs (assessed with Attention Deficit Hyperactivity Disorder Rating Scale-IV and Connor's Global Impression-Parent). A mixed-effects regression model evaluated the effects of patch wear time on sleep and symptom measures. Patch wear time exerted no significant effect on sleep latency or total sleep time, although a trend toward improved sleep quality was evident (P = 0.059) with longer patch wear times. Sleep parameters were not adversely affected by longer methylphenidate transdermal system patch wear times. Thus, if replicated in larger samples, the individualization of patch wear times should be considered according to the needs and responses of patients.     

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.     

Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder

Object?ves. Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) includes stimulant and non-stimulant medications. Our purpose in this study is to investigate efficacy, safety and tolerability of combined methylphenidate and atomoxetine pharmacotherapy. Methods. We included 12 patients of the 824 patients with ADHD using methylphenidate and atomoxetine combined therapy between the years 2010 and 2014. Kiddie-SADS, Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale, Child Behavior Checklist, Clinic Global Impression Scale Severity and Impression (CGIS-S-I) scales were used. Results. Patients were between the ages of 7 and 17 years. Before combined pharmacotherapy the CGIS-S score mean was 5.08. Mean CGIS-S score after the combined pharmacotherapy was 3.08 (P = 0.03; –2,980). The most common side effects were irritability (n = 5, 41.6%), appetite reduction (n = 3, 25%), palpitations (n = 2, 16.7%), headache (n = 1, 8.3%). Conclus?ons. Nine of these 12 patients showed significant improvement in their symptoms, combined therapy enhanced the effectiveness of monotherapy.     

Effects of methylphenidate in auditory processing evaluation of children and adolescents with attention deficit hyperactivity disorder

PURPOSE: To compare the performance of a group of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) pre and post-methylphenidate use in a behavioral auditory processing test battery (AP). METHOD: Twenty-nine subjects, male and female, ranging from 7 to 15 years old have undergone different behavioral auditory processing tests. A control group composed of 29 subjects with and without learning disabilities was also evaluated. RESULTS: The group with ADHD had a performance similar to the control group without learning disabilities which improved after medication. The group with learning disabilities and without ADHD had the worst performance in tests while the group without learning disabilities and without ADHD exhibited the best ones. CONCLUSION: The AP battery was unable to distinguish ADHD patients from paired controls; the use of methylphenidate improved the performance on AP tests of ADHD group in the post-medication evaluation.     

哌甲酯控释片对注意力缺陷多动障碍患儿身高和体质量的影响

目的 观察哌甲酯控释片对注意力缺陷多动障碍(ADHD)患儿身高和体质量的影响,旨在为哌甲酯的临床应用提供参考.方法 回顾性分析2007-01-12郑州市儿童医院收治的资料完整的94例ADHD患儿病例资料,男65例(69.1%),女29例(30.9%);混合型80例(85.1%),注意缺陷为主型14例(14.9%).记录每例患儿性别、年龄、临床亚型、哌甲酯控释片剂量.测量诊断时和随访6、12、18、24、30、36、42、48个月时身高和体质量.采用SPSS 17.0统计学软件进行处理.结果 随着随访时间的延长,患儿哌甲酯剂量逐渐增加,体质量指数(BMI,z值)从随访6个月开始逐渐降低,直到随访36个月才逐渐恢复.体质量(z值)从开始治疗逐渐下降,至随访18个月达到最低点,此后逐步回升.身高(z值)也从开始治疗逐渐下降,至随访30个月达到最低点,此后逐步回升.从绝对值来看,随着随访时间得延长患儿平均体质量和身高逐渐增加.诊断时患儿平均体质量低于预期体质量0.697 kg,随访30个月时与预期体质量差距扩大到4.274 kg,此后差距逐渐缩小,直到随访48个月时差距缩小到1.588 kg.诊断时患儿平均身高低于预期身高0.42 cm,随访30个月时与预期身高差距扩大到2.69 cm,此后差距逐渐缩小,直到随访48个月时差距缩小到0.83 cm.结论 短期观察证实哌甲酯对ADHD患儿体质量和身高存在负面影响,长期临床观察发现ADHD患儿存在增长反弹趋势,哌甲酯对ADHD患儿生长曲线的影响可能随时间推移呈逐步衰减过程.     

High-dose methylphenidate treatment of attention deficit hyperactivity disorder in a preschooler

Although attention deficit hyperactivity disorder is thought to be present in preschoolers, there are no clear guidelines for dosing stimulant medications in this population. This is a case of a 4-year-old boy who was given 108 mg/day extended-release methylphenidate (OROS) MPH) (6.1 mg/kg/day) by his caregiver with notable behavioral improvement. However, weight loss incurred due to the anorexic side effect of the medication led the clinician to decrease his dose to 72 mg/day OROS MPH (3.7 mg/kg/day). The case highlights that some young children with attention deficit hyperactivity disorder treated with MPH may require higher doses than would be predicted by weight-based dosing. An increased frequency of side effects associated with high doses of MPH necessitates that the clinician balance the positive behavioral response of the medication with adverse side effects in determining ideal dose.     

Transferrin in korean children with attention deficit hyperactivity disorder

Objective

The aim of the present study was to investigate the relationship between iron, ferritin, transferrin, total iron binding capacity (TIBC), hemoglobin, mean corpuscular volume (MCV) mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in children with ADHD.

Methods

MethodsaaThe sample consisted of 48 ADHD children and sex and age matched control children (a couple of 28 boys, 22 girls; age 6-8 years; mean±SD, 6.98±0.39). We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated subjectively with Conners'' Parent Rating Scales, Dupaul Parent ADHD Rating Scales. Subjects with ADHD and control were evaluated the hematology test including the iron, transferrin, MCV etc. Paired t test were used to evaluate the relation of a lot of hematology findings between ADHD and control group.

Results

The serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of ADHD group were respectively 80.92±33.33 ug/dL, 35.81±16.59 ng/mL, 248.42±44.15 mg/dL, 351.69±102.13 ug/dL, 12.78±0.71 g/dL, 82.94±2.58 fL, 27.18±1.12 uug, 32.79±1.12%. Otherwise the serum iron, ferritin, transferrin, TIBC, hemoglobin, MCV, MCH, and MCHC of control group were respectively 82.04±28.14 ug/dL, 37.05±18.28 ng/mL, 266.27±25.40 mg/dL, 352.77±89.54 ug/dL, 12.77±0.70 g/dL, 81.81±2.96 fL, 26.69±0.99 uug, 32.66±0.96%. A significant difference were found in the transferrin(t=2.63, p=0.011), MCV (t=2.19, p=0.034), and MCH (t=2.18, p=0.034).

Conclusion

These results suggested that lower transferrin levels might be related with ADHD symptoms.     

注意缺陷多动障碍执行功能的研究进展

注意缺陷多动障碍(attention deficit hyperactivity disorder, ADHD)是儿童时期常见的中枢神经系统疾病,其主要表现为注意力不集中、多动及冲动.西方国家患病率为3%～5%之间,国内患病率为3%～10%.ADHD的症状可以造成儿童的学习、人际关系、社交等多个领域的功能明显缺损,部分儿童的症状还可以持续至成年而不愈,成为成人ADHD.     

Executive dysfunctions in children with attention deficit hyperactivity disorder

One hundred and twenty-four male children ranging in age from seven to 12 years-old were selected. The sample was divided into two groups: (1) sixty-two with attention deficit hyperactivity disorder (ADHD) children; and (2) sixty-two normal matched controls (N-ADHD). Three tests were individually administered: (1) Wisconsin Card Sorting Test (WCST); (2) Verbal fluency and semantics (animals and fruits); and, (3) Picture Arrangement subtest of the WISC-R. For all the test scores, statistically significant differences were found between both ADHD and N-ADHD groups. Two separate factor analyses were performed, using the normal and ADHD groups. Four factors were found for the N-ADHD group, which accounted for 85.7% of the variance. The factor structure presented some similarities in both groups: Factor 2, 3 and 4 in the control group corresponded to factors 1, 2 and 3 in the ADHD group. Nonetheless, in the ADHD group Factor 1 (Abstraction and Flexibility Factor) was absent. Results are interpreted as supporting the hypothesis of executive dysfunction in children with ADHD.     

Fenfluramine and methylphenidate in children with mental retardation and attention deficit hyperactivity disorder: Laboratory effects

Twenty-eight children took part in a double-blind, placebo-controlled, crossover study of fenfluramine and methylphenidate. Fenfluramine dosage was gradually increased to a standardized dose of 1.5 mg/kg per day, whereas methylphenidate was given in doses of 0.4 mg/kg per day. The children were assessed on laboratory tests of selective and sustained attention, visual matching, and color matching, during which seat activity was monitored automatically. Results showed fenfluramine to be superior to placebo on the memory task, whereas methylphenidate reduced commission errors on a continuous performance test. Methylphenidate caused shorter response times, and fenfluramine caused increases, on two of the tests. Examiner behavior ratings indicated significant improvements with both drugs on the domains of attention, activity level, and mood. These findings, together with those from a companion clinical study, suggest that the drugs may have contrasting mechanisms of action, but both appear to have useful clinical effects in these children.This work was supported by a research project grant from the National Institute of Mental Health (Grant MH 44122) to M. G. Aman and by grants awarded to the Ohio State University Nisonger Center for Mental Retardation and Developmental Disabilities from the U.S. Department of Health and Human Services, Office of Human Developmental Disabilities (Grant 07DD0270/16) and Bureau of Maternal and Child Resources Development, Division of Maternal and Child Health (Grant MCJ 922). The authors thank Johannes Rojahn Elaine Marshburn, and Deborah Rinto for logistical support during this project, and Mary Beth DeWitt for assistance with the statistical analysis.     

Somatosensory functioning in children with attention deficit hyperactivity disorder

In older to test the hypothesis that attention deficit hyperactivity disorder (ADHD) is related to deficits in somatosensory processing, 49 ADHD male children and 49 matched controls were tested on a wide range of tactile tasks, and somatosensory evoked potentials (SEP) were also recorded. In addition, parents' and teachers' ratings on the children's typical responses to tactile stimuli were obtained. The results show that the ADHD children were less skilled on suprathreshold, but not on threshold tasks than were the controls. Further, a larger percentage of ADHD children were 'tactile defensive'. Finally, the ADHD children showed Iarger-than-normal amplitudes of late, but not early components of the SEP. These data suggest that some aspects of somatosensory processing by ADHD children are deficient.     

Parental rating of sleep in children with attention deficit/hyperactivity disorder

Objective  Sleep problems have often been associated with attention deficit/hyperactivity disorder (ADHD). Parents of those with ADHD and children with ADHD report sleep difficulties more frequently than healthy children and their parents. The primary objective of this paper is to describe sleep patterns and problems of 5 to 11-year-old children suffering from ADHD as described by parental reports and sleep questionnaires. Method  The study included 321 children aged 5–11 years (average age 8.4 years); 45 were diagnosed with ADHD, 64 had other psychiatric diagnoses, and 212 were healthy. One hundred and ninety-six of the test subjects were boys and 125 were girls. A semi-structured interview (Kiddie-SADS-PL) was used to DSM-IV diagnose ADHD and comorbidity in the clinical group. Sleep difficulties were rated using a structured sleep questionnaire (Children Sleep Behaviour Scale). Results  Children diagnosed with ADHD had a significantly increased occurrence of sleep problems. Difficulties relating to bedtime and unsettled sleep were significantly more frequent in the ADHD group than in the other groups. Children with ADHD showed prolonged sleep onset latency, but no difference was shown regarding numbers of awakenings per night and total sleep time per night. Comorbid oppositional defiant disorder appeared not to have an added effect on problematic behaviour around bedtime. Conclusion  Parents of children with ADHD report that their children do not sleep properly more often than other parents. The ADHD group report problems with bedtime resistance, problems with sleep onset latency, unsettled sleep and nightmares more often than the control groups. It may therefore be relevant for clinicians to initiate a closer examination of those cases reporting sleep difficulties.     

Treatment of attention deficit hyperactivity disorder in children

Objective The present study investigated the predictive power of anxiety, IQ, severity of ADHD and parental depression on the outcome of treatment in children with ADHD. Method Fifty children with ADHD (ages 8–12) were randomized to a 10-week treatment of methylphenidate or to a treatment of methylphenidate combined with multimodal behavior therapy. Prior to treatment predictors were assessed. Outcome was assessed separately for parents and teachers on a composite measure of inattentive, hyperactive, oppositional- and conduct disorder symptoms. Results There was neither a significant difference between the two treatments at baseline nor did treatment condition predict outcome. Therefore the data were collapsed across the two treatments. A combination of anxiety and IQ predicted teacher-rated outcome, explaining 18% of the variance. Higher anxiety and higher IQ’s indicated better treatment outcome. There were no significant predictors of the parent-rated outcome. Conclusion This study showed a small but significant predictive effect of IQ and anxiety on treatment outcome in children with ADHD. Clinical implications This study supports the idea that for the treatment of ADHD children with comorbid anxiety and higher IQ respond better to the two most used treatments for ADHD.     

The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder

OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal cortical functioning. However, these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms. METHOD: The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a randomized, double-blind, placebo-controlled pharmacological challenge with methylphenidate in 15 adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages 12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who were scanned during both a methylphenidate and a placebo session. Fourteen healthy comparison subjects (ages 12-20) who were not given methylphenidate served as the primary comparison group. RESULTS: During the divided attention task, unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects. Methylphenidate led to an increase in activation in this region but had no effect on task performance. Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects, but methylphenidate did not have a direct effect on activation in this region. CONCLUSIONS: These results suggest that ADHD is associated with abnormal processing in attentional networks, with specific dysfunction in striatal circuitry. Methylphenidate may act to normalize activity within this network.