ADHD Rating Scale-IV Research Articles

Questionnaire-based assessment of behavioral problems in Japanese children with epilepsy

Behavioral problems in Japanese children with epilepsy were investigated by means of a questionnaire for parents consisting of three checklists: the Child Behavior Checklist (CBCL)/4–18 Japanese Edition, the High-Functioning Autism Spectrum Screening Questionnaire (ASSQ), and the Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (ADHD-RS) for parents. The participants were the parents of 108 children aged 6–18years with apparently normal intelligence. The CBCL indicated abnormal behavior in 10.5 to 35.6% of the children, and T scores on both the internalizing and externalizing scales had a significant positive relation with scores on the ASSQ and ADHD-RS. It was revealed through multivariate logistic regression analysis that the persistence of seizures was significantly related with abnormality on the externalizing scale of the CBCL (p=0.010, odds ratio: 3.48, 95% confidence interval: 1.34–9.02). Future studies are needed to determine whether seizure freedom improves behavior in children with epilepsy.

Parent-Reported Executive Function Behaviors and Clinician Ratings of Attention-Deficit/Hyperactivity Disorder Symptoms in Children Treated with Lisdexamfetamine Dimesylate

The purpose of this article was to describe the relationships between parent-rated executive function (EF) and clinician-rated attention-deficit/hyperactivity disorder (ADHD) symptoms before and after lisdexamfetamine dimesylate (LDX) treatment in children with and without EF deficit. In post-hoc analyses of children with ADHD who participated in a 7 week open-label, dose-optimized (LDX 20-70 mg/day) trial, ADHD Rating Scale-IV (ADHD-RS-IV) change scores were compared (using two-sample t tests) between youth with and without clinically significant EF impairment at baseline. Clinically significant impairment was defined as parent-rated Behavior Rating Inventory of EF (BRIEF) Global Executive Composite (GEC) t scores ≥65. Relationships between baseline and endpoint BRIEF and ADHD-RS-IV scores were examined using Pearson correlations and generalized effect linear model. Safety assessment included treatment-emergent adverse events (TEAEs). At baseline, 265/315 participants (84.1%) had a clinically significant BRIEF score. Their mean (SD) ADHD-RS-IV total score at baseline was 42.1 (6.64) for those with, and 36.5 (6.67) for those without, clinically significant BRIEF. At endpoint, ADHD-RS-IV total and subscale scores were significantly improved (p<0.0001) for both those with and those without clinically significant baseline BRIEF scores. Moderately strong, positive Pearson correlations were observed between BRIEF and ADHD-RS-IV total and subscale scores. In the generalized effect linear model, ADHD-RS-IV change scores were significantly correlated with endpoint BRIEF scores (r(2)=0.35, β=0.73, p<0.0001). In the subgroup without clinically significant BRIEF t scores at endpoint, parents and clinicians rated 90% and 95%, respectively, as improved. In the subgroup with clinically significant BRIEF t scores at endpoint, parents and clinicians rated 69% and 78%, respectively, as improved. TEAEs were experienced by 269/318 (84.9%) participants; most (82.7%) experienced events mild to moderate in intensity. A total of 12/318 (4.1%) participants discontinued because of TEAEs. Clinically significant impairment of EF behaviors in children with ADHD was associated with more severe ADHD symptoms. LDX therapy improved ADHD symptom severity, and at endpoint, fewer participants displayed impairment of EF behaviors (versus baseline). The parent-rated BRIEF may describe clinically important EF behaviors not assessed by the 18-item ADHD-RS-IV.

Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

BackgroundDespite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD.MethodsIn a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an “optimal” LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission.ResultsFour hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits.ConclusionIn the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months.Trial registrationClinical Trial Numbers: NCT00334880 and NCT01070394Clinical Trial Registry: clinicaltrials.govURLshttp://www.clinicaltrials.gov/show/NCT00334880http://www.clinicaltrials.gov/ct2/show/NCT01070394?term=NCT01070394&rank=1

Feasibility and efficacy of yoga as an add-on intervention in attention deficit-hyperactivity disorder: An exploratory study

Context:Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders. Stimulant medication is frequently used in management, with significant adverse effects. There is a growing interest in complementary treatments like yoga.Aims:To study the effects of yoga as a complementary therapy in children with moderate to severe ADHD.Settings and Design:The study was performed on children (consent was taken from parents) admitted in a child psychiatry unit using an open-label exploratory study.Materials and Methods:Children between 5 and 16 years of age diagnosed with ADHD and co-operative for yoga were included. Subjects with other serious psychiatric and medical illnesses were excluded. The participants were given yoga training daily during their in-patient stay. They were rated on Conners’ abbreviated rating scale – (CARS), ADHD-rating scale–IV (ADHD - RS IV) and clinical global impression (CGI)-Severity, at the beginning of study, at discharge and subsequently at the end of 1st, 2nd and 3rd month by a research associate not involved in yoga instruction. Paired t-test was employed to compare the means of scores between baseline and follow-ups.Results:A total of 9 children (8 males, 1 female) were recruited into the study. All, but one were on medications. An average of 8 yoga training sessions was given to subjects. They were able to learn yoga reasonably well. There was a significant improvement in the ADHD symptoms as assessed on CARS (P-0.014), ADHD-RS IV (P=0.021) and CGI- S scales (P=0.004) at the time of discharge.

Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.

Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children

Atomoxetine, a selective inhibitor of the norepinephrine transporter, exerts its therapeutic effect for attention-deficit hyperactivity disorder (ADHD) by increasing the concentration of synaptic norepinephrine. The objective of this study was to evaluate the association of the genetic variants of multiple genes of the noradrenergic neurotransmitter system with atomoxetine response. One hundred and eleven ADHD children and adolescents were enrolled in a prospective, open-label study of atomoxetine for 8-12weeks. The dose was titrated to 1.2-1.4mg/kg per day and maintained for at least 4weeks. The primary efficacy measure was the investigator-rated ADHD Rating Scale-IV. Two categorical evaluations of treatment effects (defined as response and remission) were used. Twelve SNPs in SLC6A2, ADRA2A, and ADRA1A were genotyped to analyze their association with response or remission status. rs3785143 in SLC6A2 was associated with responder status (nominal P=0.0048; corrected by multiple test, P=0.0416; OR 2.66, 95% confidence interval (CI) 1.35-5.26). rs2279805 of SLC6A2 was nominally significantly associated with the remission status. (P=0.0221, OR 2.32, 95% CI 1.13-4.75, multiple test P=0.2130). The GG haplotype of rs1800544 and rs553668 in ADRA2A achieved nominal significance for association with non-remission (P=0.0219, OR 2.82, 95% CI 1.16-6.85, multiple test, P=0.2076). The results of this study suggest that DNA variants of both SLC6A2 and ADRA2A in the adrenergic neurotransmitter system might alter the response to atomoxetine, though further replication study in larger sample for validation of these findings is still needed.

Dopaminergic and Noradrenergic Gene Polymorphisms and Response to Methylphenidate in Korean Children with Attention-Deficit/Hyperactivity Disorder: Is There an Interaction?

We aimed to investigate the independent and interaction effects of dopamine transporter gene (DAT1), dopamine D4 receptor gene (DRD4), alpha-2A adrenergic receptor gene (ADRA2A), and norepinephrine transporter gene (NET1), with regard to treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). The participants of the study were 103 children and adolescents (ages 9.1±2.1 years) diagnosed as having ADHD according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria. They were enrolled in an 8-week, open-label trial of MPH. The good responder group was defined as subjects having an ≥50% decrease in the ADHD Rating Scale-IV (ADHD-RS) total score from the baseline, and at the same time a Clinical Global Impressions-Improvement Scale (CGI-I) score of 1 or 2, both at the 8th week of MPH treatment. Multivariate stepwise logistic regression was performed to examine the independent and interaction effects of genotypes on the dichotomized MPH treatment response. Significant interaction effects on MPH response were detected between the genotypes of the DRD4 variable number of tandem repeat (VNTR) polymorphisms and those of either the ADRA2A DraI or the NET1 -3081(A/T) polymorphisms; significant interaction effects were also detected between the genotypes of the ADRA2A DraI polymorphisms and those of either the NET1 G1287A or the NET1 -3081(A/T) polymorphisms (Nagelkerke R(2)=0.40). No significant independent effect of a genotype was detected according to the stepwise logistic regression results. The results suggest that genes involved in the dopaminergic and noradrenergic systems might interact to form important predictors of short-term response to MPH.

12주 OROS-Methylphenidate 약물 치료 후 ADHD 아동의 삶의 질 변화

Objectives : The aim of this study is to investigate the effectiveness of treatment with osmotic-release oral system methylphenidate (OROS-MPH) on quality of life (QOL) in children with attention-deficit hyperactivity disorder (ADHD). Another aim is to assess the relationship between change in QOL and other factors including children's symptoms and academic performance or parents' depression and parenting stress. Methods : A total of 111 medication-naive children with ADHD in a multicenter, open-label, 12-week trial of OROS-MPH completed an evaluation using diverse rating scales at two time points; at baseline and after 12 weeks of treatment. Scales for investigation of children included the Parent Report Form-Children's Health and Illness Profile-Children's Edition (PRF-CHIP-CE) on QOL, the ADHD Rating Scale-IV on symptoms, and the Academic Performance Rating Scale (APRS). The Beck Depression Inventory and Parenting Stress Index were used for assessment of their parents. Results : Total scores for mean PRF-CHIP-CE increased from <TEX>$207.9{\pm}26.7$</TEX> at baseline to <TEX>$226.3{\pm}25.9$</TEX> after 12 weeks of treatment (p<.001). The change of APRS showed the strongest correlation with the increment of PRF-CHIP-CE scores (Pearson coefficient=0.561, p<.001), even after controlling for other factors (partial correlation coefficient=0.420, p<.001). Conclusion : Treatment with MPH-OROS results in improvement of QOL in children with ADHD in Korea. The advance in academic performance plays a key role in this change of QOL.

Methylphenidate Transdermal System in Attention-Deficit Hyperactivity Disorder in Adolescentsy

Attention-deficit hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity.[2] Globally, ADHD affects approximately 5–10% of children[3] and persists into adolescence in up to 85% of affected individuals.[4] Psychostimulants, such as methylphenidate and amfetamine, are the mainstay of treatment in ADHD.[2] A patch that delivers methylphenidate transdermally (methylphenidate transdermal system; Daytrana®) has been developed for the treatment of ADHD. The patch comprises a backing layer, an adhesive formulation that incorporates methylphenidate and uses DOT Matrix™ technology, and a protective liner, which is removed prior to application.[5] The features and properties of methylphenidate transdermal system (including available patch sizes and the nominal methylphenidate dose delivered by each patch size) are shown in table I. Once applied to the skin, methylphenidate transdermal system releases methylphenidate continuously. A potential advantage of this patch technology is that it allows the duration of the effect to be tailored to the individual by varying the duration of the application (‘wear time’).[6] Table I Features and properties of methylphenidate transdermal system (Daytrana®)[1] Methylphenidate transdermal system is approved in the US for the treatment of ADHD,[5] and its use in children aged 6–12 years with ADHD has been reviewed previously.[7] This profile report examines the use of methylphenidate transdermal system in adolescents aged 13–17 years with ADHD. Adolescents aged 13–17 years with ADHD were randomized to receive methylphenidate transdermal system or placebo transdermal system in a double-blind, multicenter, 7-week trial (core trial).[8] During a 5-week dose-optimization period, patients were titrated to their optimal methylphenidate transdermal system dosage (10, 15, 20, or 30 mg); the dose-optimization period was followed by a 2-week maintenance period, during which patients continued treatment at their optimal dosage. Patches were applied to the hip each morning and worn for 9 hours per day.[8] Following the core trial, eligible patients could receive longer-term therapy with methylphenidate transdermal system 10–30 mg in a noncomparative extension study of ≈6 months duration.[9] According to the results of the core trial, methylphenidate transdermal system 10–30 mg was effective in adolescents aged 13–17 years with ADHD.[8] The mean ADHD-Rating Scale-IV (ADHD-RS-IV) total score (primary endpoint) decreased to a significantly (p < 0.001) greater extent in adolescents receiving methylphenidate transdermal system (n = 143) than in those receiving placebo transdermal system (n = 72), with a least squares mean between-group difference of -9.96 (95% CI -13.39, -6.53). The mean ADHD-RS-IV total score at study end was 17.7 in methylphenidate transdermal system recipients and 27.7 in placebo transdermal system recipients; the mean baseline scores were 36.4 and 36.6 in the corresponding treatment groups.[8] In the extension study, methylphenidate transdermal system recipients experienced a significant (p < 0.001) reduction from the start of the core trial in the mean ADHD-RS-IV total score of 23.0.[9] Methylphenidate transdermal system was generally well tolerated in adolescents with ADHD. The vast majority of treatment-emergent adverse events were of mild to moderate severity in both the short-term core trial[8] and the longer-term extension study.[9] In the core trial, the most frequently reported treatment-emergent adverse events (occurring in ≥5% of methylphenidate transdermal system recipients and in numerically more methylphenidate transdermal system than placebo transdermal system recipients) included decreased appetite, irritability, upper respiratory tract infection, nausea, insomnia, dizziness, and decreased weight.[8] A similar tolerability profile was seen during the extension study.[9] In the core trial, most of the skin reactions to methylphenidate transdermal system comprised mild erythema, and adherence of the methylphenidate transdermal system patch to the skin was rated at ≥90% overall.[8] Changes in the blood pressure and pulse rate observed in the core[8] and extension[9] studies were typical of those seen in patients receiving stimulants.

Impact of attention deficit hyperactivity disorder-like symptoms on the clinical features of adolescents with pervasive developmental disorders

Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms are common among children and adolescents with Pervasive Developmental Disorders (PDD). The purpose of this study was to assess the impact of ADHD-like symptoms on the clinical features of adolescents with PDD. A total of 72 subjects (between the ages of 12 and 17) diagnosed as having PDD were split into higher (ADHD+) and lower (ADHD-) groups according to the presence of ADHD-like symptoms as assessed with the Japanese version of the ADHD Rating Scale-IV (ADHD-RS-IV-J). Group differences in coexisting psychopathology, as assessed by the eight subscales of the Japanese version of the Child Behavior Checklist for Ages 4-18 (CBCL/4-18-J) and autistic core features, as assessed by the adolescent part of the PDD-Autism Society of Japan Rating Scale (PARS), were examined. The ADHD + subjects showed a significantly higher degree of general psychopathology, including both externalizing and internalizing symptoms, as compared to subjects in the ADHD- subgroup. Additionally, the ADHD + subgroup showed greater impairment according to PARS scores. These results indicate an important role of ADHD-like symptoms in PDD. Therefore, parents/caregivers may find it useful to know to what extent their child's ADHD-like symptoms deviate from the norm for PDD adolescents and the implications of these symptoms for long-term care. In addition, clinicians would be well advised to consider further systematic assessment of ADHD-like symptoms.

Construct Validity of ADHD/ODD Rating Scales: Recommendations for the Evaluation of Forthcoming DSM-V ADHD/ODD Scales

Exploratory structural equation modeling (SEM) was applied to a multiple indicator (26 individual symptom ratings) by multitrait (ADHD-IN, ADHD-HI and ODD factors) by multiple source (mothers, fathers and teachers) model to test the invariance, convergent and discriminant validity of the Child and Adolescent Disruptive Behavior Inventory with 872 Thai adolescents and the ADHD Rating Scale-IV and ODD scale of the Disruptive Behavior Inventory with 1,749 Spanish children. Most of the individual ADHD/ODD symptoms showed convergent and discriminant validity with the loadings and thresholds being invariant over mothers, fathers and teachers in both samples (the three latent factor means were higher for parents than teachers). The ADHD-IN, ADHD-HI and ODD latent factors demonstrated convergent and discriminant validity between mothers and fathers within the two samples. Convergent and discriminant validity between parents and teachers for the three factors was either absent (Thai sample) or only partial (Spanish sample). The application of exploratory SEM to a multiple indicator by multitrait by multisource model should prove useful for the evaluation of the construct validity of the forthcoming DSM-V ADHD/ODD rating scales.

Bupropion versus methylphenidate in the treatment of children with attention‐deficit/hyperactivity disorder: randomized double‐blind study

To compare the safety and efficacy of bupropion with methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). In a 6-week randomized double-blind study, 44 patients with a DSM-IV-TR diagnosis of ADHD were randomly assigned to receive bupropion 100-150 mg/day (100 mg/day for <30 kg and 150 mg/day for >30 kg) or methylphenidate 20-30 mg/day. Symptoms were assessed using Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6. Forty patients had at least one post-baseline measurement, and 38 patients completed the trial. No significant difference was found between the two groups on the Parent and Teacher ADHD-RS-IV scores ([F(1, 38) = 0.266, p = 0.609] and [F(1, 38) = 0.001, p = 0.972], respectively). By week 6, 18 patients (90%) in each group achieved response on the Parent scale (Fisher's exact test p-value = 1.0). With the Teacher ADHD-RS-IV used, eight (40%) patients in the bupropion group and 12 (60%) patients in the methylphenidate group achieved response by week 6 (χ(2) (1) = 1.600, p = 0.206). Headache was observed more frequently in the methylphenidate group. Frequency of other side effects was not significantly different between the two groups. Bupropion has a comparable safety and efficacy profile with methylphenidate in children and adolescents with ADHD.

The Effects of Lisdexamfetamine Dimesylate on Emotional Lability in Children 6 to 12 Years of Age With ADHD in a Double-Blind Placebo-Controlled Trial

Objective: To evaluate the effect of lisdexamfetamine dimesylate (LDX) on emotional lability (EL) in children with ADHD. Method: Post hoc analyses of a placebo-controlled trial of LDX-stratified children (aged 6-12 years) with ADHD to prominent and not prominent EL at baseline (score >3 or ≤3, respectively, on Conners’ Parent Rating Scale [CPRS] items of anger, loss of temper, and irritability). Efficacy was assessed by change in CPRS EL scores and ADHD Rating Scale-IV (ADHD-RS-IV) total and subscale scores. Safety measures included treatment-emergent adverse events (TEAEs). Results: LDX showed improvement versus placebo (p < .0005) for EL item least squares (LS) mean change scores at endpoint and throughout the day. At baseline, 138 and 73 participants randomized to LDX treatment and having baseline and endpoint CPRS scores were categorized with CPRS-derived prominent and not prominent baseline EL, respectively; 41 and 31 participants randomized to placebo were categorized with CPRS-derived prominent and not prominent baseline EL, respectively. ADHD-RS-IV total and subscale scores decreased with LDX regardless of baseline EL severity. TEAEs included decreased appetite, insomnia, upper abdominal pain, headache, and irritability. Conclusion: EL and ADHD symptoms improved with LDX regardless of baseline EL symptom severity. LDX demonstrated a safety profile consistent with long-acting psychostimulant use.

Anxiety in Young People With ADHD

Objective: (a) To determine the prevalence of comorbid anxiety disorder in ADHD, defined by diagnostic criteria and (b) to compare anxiety as reported by parents and participants with clinician assessment. Method: Children with ADHD were assessed for comorbid anxiety disorder using the Anxiety Disorder Interview Schedule for Children. Parent report (Conners’ Parent Rating Scale–Revised: Long version) and self-report (State-Trait Anxiety Inventory and Brain Resource Inventory for Screening Cases–Child version) scales were used to assess anxiety. The ADHD–Rating Scale IV was used to measure ADHD symptoms. Results: Of 134 participants (11.0 ± 2.6 years), 31.3% had comorbid anxiety disorder. Comorbid anxiety disorder was associated with greater severity of ADHD. Anxiety symptoms from parent reports (p < .05) but not from child/self-report (p > .05) correlated with clinician assessment. Conclusion: Assessment for comorbid anxiety disorder and inclusion of parent rating in this assessment are important components of ADHD treatment in children and adolescents.

Maintenance of Efficacy of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder

To evaluate lisdexamfetamine dimesylate maintenance of efficacy in adults with attention-deficit/hyperactivity disorder (ADHD). Adults (aged 18-55 years) who had ADHD meeting DSM-IV-TR criteria, baseline ADHD Rating Scale-IV (ADHD-RS-IV) with adult prompts total scores of < 22, and Clinical Global Impressions-Severity of Illness (CGI-S) ratings of 1, 2, or 3 were enrolled. After previously receiving commercially available lisdexamfetamine dimesylate (30, 50, or 70 mg/d) for ≥ 6 months with acceptable tolerability and maintaining response during a 3-week open-label phase at a stable lisdexamfetamine dimesylate dose, the participants entered a 6-week double-blind randomized withdrawal phase on treatment with lisdexamfetamine dimesylate (same dose) or placebo. Data were collected from April 2009 to July 2010. The primary outcome was the proportion of participants having symptom relapse (≥ 50% increase in ADHD-RS-IV score and ≥ 2 rating-point increase in CGI-S score). A total of 116 participants were randomized (lisdexamfetamine dimesylate n = 56; placebo n = 60). At the randomized withdrawal phase baseline, mean (SD) ADHD-RS-IV scores for lisdexamfetamine dimesylate and placebo were 10.6 (4.96) and 10.6 (4.82), respectively. At endpoint, 8.9% (5/56) of adults taking lisdexamfetamine dimesylate and 75.0% (45/60) taking placebo (P < .0001) showed symptom relapse; most showed relapse after 1 and 2 weeks of the randomized withdrawal phase (4 and 0 adults taking lisdexamfetamine dimesylate, 26 and 10 taking placebo, respectively). During the randomized withdrawal phase, treatment-emergent adverse events were reported in 48.2% and 30.0% of participants in the lisdexamfetamine dimesylate and placebo groups, respectively. Treatment-emergent adverse events with incidence ≥ 5% in the lisdexamfetamine dimesylate and placebo groups were headache (14.3% and 5.0%), insomnia (5.4% and 5.0%), and upper respiratory tract infection (8.9% and 0%). In adults with ADHD on medium- to long-term treatment, lisdexamfetamine dimesylate demonstrated maintenance of efficacy vs placebo upon randomized withdrawal. A majority of patients given placebo showed symptom relapse by 2 weeks. The safety profile of lisdexamfetamine dimesylate was generally consistent with previous lisdexamfetamine dimesylate studies. ClinicalTrials.gov identifier: NCT00877487.

Association between glycogen synthase kinase-3β gene polymorphisms and attention deficit hyperactivity disorder in Korean children: A preliminary study

Glycogen synthase kinase (GSK)-3β plays a key role in the phosphorylation and regulation of metabolic enzymes and many transcription factors. Recent studies have suggested the involvement of GSK-3β in the pathogenesis and treatment target of DA-associated neuropsychiatric disorders, which has led to consider GSK-beta as one of the candidate genes for those disorders. GSK-3β genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association between -1727A/T and -50T/C SNPs of GSK-3β gene with ADHD. All ADHD subjects completed a comprehensive and standardized diagnostic test and psychological evaluation battery, including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 103 ADHD patients and 173 normal controls were analyzed for -1727A/T and -50T/C SNPs of GSK-3β gene. There were statistically significant differences in the genotype distributions of the -1727A/T SNP of GSK-3β gene between the ADHD group and the control group. The frequency of the genotype AT was significantly higher in the ADHD patients. Concerning the haplotype, there was a significant difference in the A-C haplotype frequency between the two samples. However, no differences in either the genotype distribution or in allele frequencies of -50C/T were observed between the two samples. In the parents version of K-ARS of all subjects, ANCOVA revealed that two subscales and the total score were significantly higher in the subjects with AT+TT genotypes than those with AA genotype after adjusting for age and gender. The odds ratio for the ADHD patients was 1.79, comparing the AT genotype group with the AA genotype group. Therefore, genotype AT is associated with a higher risk of ADHD. Our results suggest that the -1727A/T SNP of GSK-3β gene may affect susceptibility in ADHD. Further investigation with a larger number of subjects is needed to validate this finding.

Efficacy of guanfacine extended release in the treatment of combined and inattentive only subtypes of attention-deficit/hyperactivity disorder.

Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. The full analysis set included 631 subjects aged 6-17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). The results support the use of GXR in the treatment of core ADHD symptoms as defined in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, including hyperactivity, impulsivity, and inattention.

Can Parent Reports Serve as a Proxy for Teacher Ratings in Medication Management of Attention-Deficit Hyperactivity Disorder?

While American Academy of Pediatrics guidelines recommend obtaining symptom reports from both parents and teachers when treating children with attention-deficit hyperactivity disorder (ADHD), information from parents is easier to obtain and practitioners may prefer to rely solely on parent report when managing medications. There are, however, few empirical data on the relationship between parent and teacher reports during medication management of ADHD. This study examined the relationship between parent and teacher reports of symptoms of ADHD during a clinical trial. A study to improve medication management of ADHD was conducted in 24 pediatric practices with 270 children. Children meeting criteria for ADHD were randomized by practice to treatment-as-usual or specialized care groups, with data combined from the groups to examine parent-teacher agreement. Parent and teacher reports on the ADHD Rating Scale-IV were obtained at pretreatment, 4 months, and 12 months follow-up. At each assessment, correlations between parent and teacher ratings were statistically significant, but the magnitudes of the correlations were low, accounting for no more than approximately 17% of the variance between measures. Correlations between change scores on parent and teacher ratings were statistically significant but low for Total and Inattentive scales and not significant for the Hyperactive-Impulsive scale. For agreement on extreme scores, 6 of 9 kappas were statistically significant but all were unacceptably low. Agreement between parent and teacher ratings of symptoms of ADHD is too low for clinicians to rely on parent reports while managing medications. Teacher reports are still needed to ensure optimal management.

Agreement among physical educators, teachers and parents on children's behaviors: A multitrait–multimethod design approach

The study examines the agreement among raters on children's problematic behaviors. A multitrait-multimethod (MTMM) matrix was applied to a normative sample of elementary school-aged children (N = 841). The participants were rated by their physical educators, using the Motor Behavior Checklist for children (MBC; Efstratopoulou, Janssen, & Simons, 2012). Teachers and parents rated the same students using the Teacher Report Form (TRF; Achenbach, 1991b), the Child Behavior Checklist (CBCL; Achenbach, 1991a) and the ADHD Rating Scale-IV (DuPaul, Power, Anastopoulos, & Reid, 1998). The resulting matrix revealed significant correlations for the Rules Breaking, Lack of Attention, Hyperactivity/Impulsivity, Lack of Social interaction problem scale and for the Internalizing, Externalizing and Total scores. Convergent validity of the specific MBC subscales was supported by significant correlations with the corresponding subscales of TRF, CBCL and ADHD Rating Scale-IV. Findings underscore the importance of taking child's settings and observer influences into account and suggest that MBC is a new promising instrument that can provide valid ratings on externalizing behavior and social problems in children when used by physical educators in school settings.

Training Executive, Attention, and Motor Skills

Objective: To examine whether cognitive enhancement can be delivered through play to preschoolers with ADHD and whether it would affect severity of ADHD symptoms. Method: Twenty-nine 4- and 5-year-old children and their parents participated in separate group sessions (3-5 children/group). Child groups were introduced games designed to enhance inhibitory control, working memory, attention, visuospatial abilities, planning, and motor skills. Parent groups were encouraged playing these games with their children at least 30 to 45 min/day and taught strategies for scaffolding difficulty levels and dealing with obstacles to daily playing. Results: Parent ratings and session attendance indicated considerable satisfaction with the program. Parent (p < .001) and teacher (p = .003) ratings on the ADHD-Rating Scale–IV (ADHD-RS-IV) indicated significant improvement in ADHD severity from pre- to post-treatment, which persisted 3 months later. Conclusion: This play-based intervention for preschoolers with ADHD is readily implemented at home. Preliminary evidence suggests efficacy beyond the termination of active treatment.