Attention-deficit/hyperactivity Disorder RS-IV Research Articles

Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial.

This is the first study to evaluate the efficacy and safety of transcranial pulse stimulation (TPS) for the treatment of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Hong Kong. This double-blind, randomized, sham-controlled trial included a TPS group and a sham TPS group, encompassing a total of 30 subjects aged 12-17 years who were diagnosed with ADHD. Baseline measurements SNAP-IV, ADHD RS-IV, CGI and executive functions (Stroop tests, Digit Span) and post-TPS evaluation were collected. Both groups were assessed at baseline, immediately after intervention, and at 1-month and 3-month follow-ups. Repeated-measures ANOVAs were used to analyze data. The TPS group exhibited a 30% reduction in the mean SNAP-IV score at postintervention that was maintained at 1- and 3-month follow-ups. TPS is an effective and safe adjunct treatment for the clinical management of ADHD. ClinicalTrials.Gov, identifier NCT05422274.

Dasotraline in adults with attention deficit hyperactivity disorder: a placebo-controlled, fixed-dose trial.

In a previous study, dasotraline demonstrated efficacy at a dose of 8 mg/day in adults with attention deficit hyperactivity disorder (ADHD). The aim of the current study was to evaluate the efficacy and safety of dasotraline in doses of 4 and 6 mg/day. Adults meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for ADHD were randomized to 8 weeks of double-blind, once-daily, fixed-dose treatment with dasotraline 4 mg/day, 6 mg/day, or placebo. The primary efficacy endpoint was changed in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy endpoints included the Clinical Global Impression, Severity (CGI-S) Scale. Least squares mean reduction at week 8 in the ADHD RS-IV HV total score was not significantly greater (vs. placebo) in the dasotraline 4 mg/day group (-15.0 vs. -13.9; n.s.; or in the dasotraline 6 mg/day group (-16.5 vs. -13.9; P = 0.074; Hochberg correction). Treatment with dasotraline 6 mg/day was significant at week 8 (uncorrected) on the ADHD RS-IV total score (P = 0.037) and the CGI-S score (P = 0.011). Treatment with the 4 mg/day dose of dasotraline was NS. Treatment with dasotraline was generally well tolerated. The results provide additional evidence that supports the potential efficacy of dasotraline, in doses of 6 mg/day, in adults with ADHD.

Population pharmacokinetic and exposure-response analyses of d-amphetamine after administration of lisdexamfetamine dimesylate in Japanese pediatric ADHD patients

Lisdexamfetamine dimesylate, a prodrug of d-amphetamine, has been approved for treatment of attention-deficit/hyperactivity disorder (ADHD). The purposes of this study were constructing a population pharmacokinetic model of d-amphetamine after dosing of lisdexamfetamine dimesylate and assessing influential factors on the pharmacokinetics of d-amphetamine in Japanese pediatric patients with ADHD. Additionally, the exposure-response relationship was evaluated for Japanese pediatric patients with ADHD using a clinical rating scale, the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score as a response index. A total of 1365 points of plasma d-amphetamine concentrations from pediatric patients (6–17 years) with ADHD in clinical studies conducted in Japan and the US were employed for the population pharmacokinetic analysis. The plasma concentrations of d-amphetamine in pediatric patients with ADHD were well described by a one-compartment model with first-order absorption and lag time. The effects of body weight and ethnicity (Japanese or non-Japanese) on apparent total body clearance and the effect of body weight on apparent volume of distribution were incorporated into the final model. No clear exposure-dependent reduction was evident from the ADHD RS-IV total score, whereas the reductions were greater for the lisdexamfetamine dimesylate treatment groups compared with the placebo group regardless of exposure to d-amphetamine.

Evidence for a Higher-Order ESEM Structure of ADHD in a Sample of Chinese Children

Exploratory structural equation modeling (ESEM) solutions have been proposed to represent the factor structures of attention-deficit/hyperactivity disorder (ADHD) in recent literature, yet no studies have assessed those structures in Chinese children. The primary aim of this study was to comprehensively examine the factor structures of the Chinese version of the ADHD Rating Scale-IV (ADHD RS-IV): Home Version. Data on 458 Chinese children aged 3–8 years (boys: 246; 54%) were used to test and compare eleven factor models: confirmatory factor analysis (CFA) models (one-factor, two-factor and three-factor), second-order CFA model, bifactor CFA models (two and three specific factors), ESEM models (two-factor and three-factor), second-order ESEM model, and bifactor ESEM models (two and three specific factors). The results showed that, overall, ESEM models displayed better fit than CFA models. Specifically, the second-order ESEM model with three first-order factors best represented of the ADHD factor structure in our sample. In addition, measurement invariance testing results showed that scalar invariance was established across gender, age and informant groups. Implications for future research are discussed.

Population pharmacokinetic and exposure-response analyses of guanfacine in Japanese pediatric ADHD patients

Guanfacine hydrochloride extended-release tablet (GXR) is approved for child and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to develop a population pharmacokinetic model of guanfacine after administration of GXR and to evaluate factors influencing the pharmacokinetics of guanfacine in pediatric ADHD patients. A population pharmacokinetic analysis was performed using 3231 plasma concentration data items of guanfacine for pediatric ADHD patients aged 6–17 years obtained from clinical studies in Japan and the US. In addition, the relationship of the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score with exposure to guanfacine was assessed for Japanese pediatric ADHD patients. A one-compartment model with first-order absorption and lag time well described the plasma concentration data of guanfacine in pediatric ADHD patients. Body weight was selected as a covariate of apparent total body clearance and apparent volume of distribution. There was no pharmacokinetic difference between Japanese and non-Japanese pediatric ADHD patients. The results suggested a tendency of exposure-dependent reduction in the ADHD RS-IV total score, whereas the reduction was observed even at low plasma exposure levels compared with the placebo group.

Dasotraline in Children with Attention-Deficit/Hyperactivity Disorder: A Six-Week, Placebo-Controlled, Fixed-Dose Trial.

Dasotraline is a potent inhibitor of presynaptic dopamine and norepinephrine reuptake with a pharmacokinetic profile characterized by slow absorption and a long elimination half-life. The aim of this study was to evaluate the efficacy and safety of dasotraline in children with attention-deficit/hyperactivity disorder (ADHD). Children aged 6-12 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomized to 6 weeks of double-blind once-daily treatment with dasotraline (2 or 4 mg) or placebo. The primary efficacy endpoint was change from baseline in the ADHD Rating Scale Version IV-Home Version (ADHD RS-IV HV) total score at week 6. A total of 342 patients were randomized to dasotraline or placebo (mean age 9.1 years, 66.7% male). Treatment with dasotraline was associated with significant improvement at study endpoint in the ADHD RS-IV HV total score for the 4 mg/day dose versus placebo (-17.5 vs. -11.4; p < 0.001; effect size [ES], 0.48), but not for the 2 mg/day dose (-11.8 vs. -11.4; ns; ES, 0.03). A regression analysis confirmed a significant linear dose-response relationship for dasotraline. Significant improvement for dasotraline 4 mg/day dose versus placebo was also observed across the majority of secondary efficacy endpoints, including the Clinical Global Impression (CGI)-Severity score, the Conners Parent Rating Scale-Revised scale (CPRS-R) ADHD index score, and subscale measures of hyperactivity and inattentiveness. Discontinuation rates due to adverse events (AEs) were higher in the dasotraline 4 mg/day group (12.2%) compared with the 2 mg/day group (6.3%) and placebo (1.7%). The most frequent AEs associated with dasotraline were insomnia, decreased appetite, decreased weight, and irritability. Psychosis-related symptoms were reported as AEs by 7/219 patients treated with dasotraline in this study. There were no serious AEs or clinically meaningful changes in blood pressure or heart rate on dasotraline. In this placebo-controlled study, treatment with dasotraline 4 mg/day significantly improved ADHD symptoms and behaviors, including attention and hyperactivity, in children aged 6-12 years. The most frequently reported AEs observed on dasotraline included insomnia, decreased appetite, decreased weight, and irritability.

Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity associated with clinically significant impairment in functioning. ADHD has an early onset, but frequently persists, with a prevalence estimate of 4% in adults. Dasotraline is a novel compound that is a potent inhibitor of dopamine and norepinephrine transporters that achieves stable plasma concentrations with once-daily dosing. In this study, adult outpatients meeting DSM-IV-TR criteria for ADHD were randomized to 4 weeks of double-blind, once-daily treatment with dasotraline 4 and 8 mg/day or placebo. The primary efficacy end point was change from baseline at week 4 in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy end points included the Clinical Global Impression, Severity (CGI-S) scale, modified for ADHD symptoms. Least squares (LS) mean improvements at week 4 in ADHD RS-IV total score were significantly greater for dasotraline 8 mg/day vs placebo (−13.9 vs −9.7; P=0.019), and nonsignificantly greater for 4 mg/day (−12.4; P=0.076). The LS mean improvements in modified CGI-S were significantly greater at week 4 for dasotraline 8 mg/day vs placebo (−1.1 vs −0.7; P=0.013), and for 4 mg/day vs placebo (−1.1 vs −0.7; P=0.021). The most frequent adverse events reported were insomnia, decreased appetite, nausea, and dry mouth. Discontinuations due to treatment-emergent adverse events were 10.3% and 27.8% of patients in 4 and 8 mg/day treatment groups, respectively. This study provides preliminary evidence that once-daily dosing with dasotraline, a long-acting, dual monoamine reuptake inhibitor, may be a safe and efficacious treatment for adult ADHD.

Evaluation of Neuropsychiatric Function in Phenylketonuria: Psychometric Properties of the ADHD Rating Scale-IV and Adult ADHD Self-Report Scale Inattention Subscale in Phenylketonuria

BackgroundPrevious qualitative research among adults and parents of children with phenylketonuria (PKU) has identified inattention as an important psychiatric aspect of this condition. The parent-reported ADHD Rating Scale-IV (ADHD RS-IV) and the Adult ADHD Self-Report Scale (ASRS) have been validated for measuring inattention symptoms in persons with attention-deficit/hyperactivity disorder (ADHD); however, their psychometric attributes for measuring PKU-related inattention have not been established. ObjectiveThe primary objective of this investigation was to demonstrate the reliability, validity, and responsiveness of the ADHD RS-IV and ASRS inattention symptoms subscales in a randomized controlled trial of patients with PKU aged 8 years or older. MethodsA post hoc analysis investigated the psychometric properties (Rasch model fit, reliability, construct validity, and responsiveness) of the ADHD RS-IV and ASRS inattention subscales using data from a phase 3b, double-blind, placebo-controlled clinical trial in those with PKU aged 8 years or older. ResultsThe Rasch results revealed good model fit, and reliability analyses revealed strong internal consistency reliability (α ≥ 0.87) and reproducibility (intraclass correlation coefficient ≥ 0.87) for both measures. Both inattention measures demonstrated the ability to discriminate between known groups (P < 0.001) created by the Clinical Global Impression-Severity scale. Correlations between the ADHD RS-IV and the ASRS with the Clinical Global Impression-Severity scale and the age-appropriate Behavior Rating Inventory of Executive Function Working Memory subscale were consistently moderate to strong (r ≥ 0.56). Similarly, results of the change score correlations were of moderate magnitude (r ≥ 0.43) for both measures when compared with changes over time in Behavior Rating Inventory of Executive Function Working Memory subscales. ConclusionsThese findings of reliability, validity, and responsiveness of both the ADHD RS-IV and the ASRS inattention scales, in addition to content validation results, support their use for the assessment of inattention symptoms among persons with PKU aged 8 years or older in both clinical and research settings.

The Effect of Methylphenidate on Neurological Soft Signs in ADHD.

ObjectiveNeurological soft signs are very common in children with the attention deficit hyperactivity disorder (ADHD), and the first line medication of this disorder is methylphenidate. The aim of the study was to assess the effect of methylphenidate on the neurological soft signs in children and adolescents suffering from ADHD depending on the dose of methylphenidate.MethodsThirty five patients with ADHD were investigated by the ADHD RS-IV parent version questionnaire and the Revised Neurological Examination for Subtle Signs before treatment adjustment and after four weeks of methylphenidate medication. The changes in hyperactivity symptomatology, neurological soft signs during therapy and the influence of the methylphenidate dose were statistically analyzed.ResultsA significant decrease in hyperactivity symptomatology was found after one month of methylphenidate medication (p=0.0001) and significant decrease in neurological soft signs was demonstrated in 21 from a total of 26 items (p<0.05). Correlation analysis showed no relationship between the dose of methylphenidate and the improvement of neurological soft signs. Similarly, the improvement of ADHD symptomatology had not correlation with the improvement of neurological soft signs.ConclusionThe study demonstrated the positive effect of methylphenidate on neurological soft signs in which improvement occurred independently of the dose, indicating that their progress may be due to methylphenidate treatment of any dose. The unrelated effect of methylphenidate on the attention deficit hyperactivity disorder and neurological soft signs suggest that methylphenidate might be useful in the therapy of clumsy child syndrome and in ADHD treatment of non-responders.

Interactions between MAOA and SYP polymorphisms were associated with symptoms of attention-deficit/hyperactivity disorder in Chinese Han subjects.

As candidate genes of attention--deficit/hyperactivity disorder (ADHD), monoamine oxidase A (MAOA), and synaptophysin (SYP) are both on the X chromosome, and have been suggested to be associated with the predominantly inattentive subtype (ADHD-I). The present study is to investigate the potential gene-gene interaction (G × G) between rs5905859 of MAOA and rs5906754 of SYP for ADHD in Chinese Han subjects. For family-based association study, 177 female trios were included. For case-control study, 1,462 probands and 807 normal controls were recruited. The ADHD Rating Scale-IV (ADHD-RS-IV) was used to evaluate ADHD symptoms. Pedigree-based generalized multifactor dimensionality reduction (PGMDR) for female ADHD trios indicated significant gene interaction effect of rs5905859 and rs5906754. Generalized multifactor dimensionality reduction (GMDR) indicated potential gene-gene interplay on ADHD RS-IV scores in female ADHD-I. No associations were observed in male subjects in case-control analysis. In conclusion, our findings suggested that the interaction of MAOA and SYP may be involved in the genetic mechanism of ADHD-I subtype and predict ADHD symptoms.

Modeling and simulation of the exposure-response and dropout pattern of guanfacine extended-release in pediatric patients with ADHD.

Guanfacine extended-release (GXR) is a selective α2A-adrenergic receptor agonist approved in the United States for once-daily administration for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents ages 6-17 years old either as monotherapy or adjunctive to stimulant medications. This analysis integrates exposure-response, placebo, and dropout data from 10 clinical trials that used GXR in adolescents and children with ADHD. In these trials, the ADHD Rating Scale-IV (ADHD RS-IV) score was collected longitudinally within patients over the course of 6-13 weeks. Non-linear mixed effects models were developed and used to describe the exposure-response of the GXR and placebo time course. The OpenBUGS program was utilized to describe the dropout time course across the trials. Placebo time course was best described by an inverse Bateman function with a 3-group mixture model that allowed for the onset and offset of the placebo response. Dropout time modeling indicated a missing at random mechanism for dropouts which was best described by a Weibull distribution with an estimated percentage of non-dropout patients. A linear exposure-response model with an adolescent effect on maximum slope (SLPmax), and a time delay for reaching SLPmax, provided the best description of the GXR exposure-response time course. The GXR exposure-response model indicated that the typical (95 % confidence interval) decrease in ADHD RS-IV score from the placebo-response trajectory would be 37.1 % (32.2, 42.0 %) per 0.1 mg/kg of GXR exposure. There was little noticeable difference between the exposure-response in adolescents and children or across ADHD subtypes.

Parent-Reported Symptoms of Attention Deficit Hyperactivity Disorder in Children with Intermittent Exotropia before and after Strabismus Surgery

PurposeTo investigate the symptoms of attention deficit hyperactivity disorder (ADHD) as reported by parents in children with intermittent exotropia [X(T)] and to determine whether strabismus surgery for X(T) affects ADHD symptoms.Materials and MethodsFifty-one consecutive children undergoing muscle surgery for X(T) were prospectively recruited. One parent of each child completed the ADHD rating scale IV (ADHD RS-IV) assessment consecutively before and one year after surgery. Patients whose preoperative scores were above the cut-off point, the 90th percentile based on a Korean sample, were regarded as demonstrating the ADHD trait. The impact of muscle surgery on ADHD symptoms was assessed by comparing the preoperative scores with the post-operative scores.ResultsEight (15.7%) of the 51 patients demonstrated the ADHD trait. ADHD RS-IV scores following strabismus surgery significantly decreased in patients with the ADHD trait (p=0.014), while they did not differ in patients without the ADHD trait. Seven (87.5%) of the 8 patients with the ADHD trait showed improvement in their ADHD RS-IV scores after surgery. There was no difference in surgical success rates between X(T) patients with and without the ADHD trait.ConclusionThe ADHD trait was relatively common in children with X(T), and the parent-reported symptoms of the children with the ADHD trait improved after strabismus surgery. These results suggest that childhood X(T) may be one contributing factor to ADHD-related symptoms.

Validez de los Criterios DSM-IV según Respuesta de los Profesores en el Diagnóstico del Trastorno por Déficit de Atención con Hiperactividad

Objective: To study the validity of each of the DSM-IV items for the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), and to look for a reduced model of items that would allow prediction of ADHD. Method: We use the information from an epidemiological study of ADHD with a sample of 1095 children. Of these, 6.6 % are ADHD cases. ADHD cases are defined according to ADHD RS-IV and DSM-IV clinical criteria. Controls are defined by exclusion. Results: The model of logistic regression that best predicts the inattentive phenotype is composed of the ADHD RS-IV (teachers’ version) items 5, 7, 13, 15 and 17 (Sensitivity: 88.7%, Specificity: 84.2%); the hyperactive / impulsive phenotype by the items 2, 4, 8 and 16 (Sensitivity: 86.4%, Specificity: 83.7%) and the combined phenotype by the items 2, 6, 15, 16 and 17 (Sensitivity: 91.6%, Specificity: 84.4%). A reduction of 72.2 % of the items in the combined phenotype is detected. Conclusions: It is possible to reduce the list of ADHD symptoms with satisfactory levels of validity and not all the items should have the same weight when making diagnostic decisions.

ADHD Rating Scale-IV en una muestra escolar española: datos normativos y consistencia interna para maestros, padres y madres

The ADHD Rating Scale-IV (ADHD RS-IV) is one of the most use scales for attention deficit hyperactivity disorder (ADHD), because has cut-off point regarding age, gender and setting, but the normalization data is based on American school samples. Evaluation of cut-off point of ADHD-RS-IV for parents and teachers in a Spanish sample. The study used the score of ADHD-RS-IV from a prevalence study of ADHD in school children of 6-12 years. Using an intrasubject design between the three evaluators (parents and teachers) and the results of each subscale (IN, H/I, and TOT) according to gender and age factors. Then, we analyzed the reliability and internal consistency for each subscale and evaluator. There are no significant differences between the father and the mother; but there are between teachers, and father and/or mother scores. In relation to gender factor, boys' score is higher on inattention and hyperactivity-impulsivity than girls'. Our results show a reversal tendency in comparison with the American samples, in our case parents' scores were significantly higher than teachers'. The use and normalization of the ADHD RS-IV will need to account not only for age, gender and setting but also for socio-cultural aspects.

Estimación de la prevalencia del trastorno por déficit de atención e hiperactividad en población normal de la isla de Mallorca

To determine the rate of prevalence of attention-deficit/ hyperactivity disorder (ADHD) in children of school age (6-11 years) in the Island of Mallorca. The epidemiological study was conducted using a community sample extracted by means of multi-stage stratified sampling according to areas (rural, city and touristy) and schooling (public, private and concerted) and consisted in 1,509 children of both sexes. The ADHD Rating Scales-IV (ADHD RS-IV) for home and school setting were used to collect data. The optimal approach to do a diagnostic evaluation, according with the literature, was using a cut-off point of 90 centil. The estimated prevalence of ADHD was 4.57% (CI at 99%: 3.0-5.8%) and we also obtained 1.26% for the hyperactive subtype, 1.06% for the disattentional subtype, and 2.25% for the combined subtype. Contrary to what was expected, prevalence was higher for females but no statistically significant. There were no statistically significant differences between levels, schools or areas. The estimates for prevalence found in this study are consistent with those reported in the literature (between 3-5%). Using the ADHD rating scale which has different cut-off point regarding age, sex and setting and the fact that it was a poblational based study could explain the higher prevalence in the females. We propose a normalization of the scales in our area in other to confirm our findings.