Attention-deficit/hyperactivity Disorder Rating Scale Research Articles

The effect of epigenome-wide DNA methylation on the association between prenatal exposure to air pollution and childhood attention-deficit hyperactivity disorder

BACKGROUND AND AIM: Prenatal exposure to air pollution including particulate matter (PM), NO2, and SO2, has been linked with attention deficit hyperactivity disorder (ADHD) in children. Epigenetic influence has been suggested to have a role in the association between exposure to air pollution and ADHD. We aimed to investigate the epigenetic effects on the association between prenatal air pollution exposure and ADHD symptoms in children. METHODS: Whole blood samples of 60 children were obtained at age 2 and 6 years repeatedly and genome-wide DNA methylation was analyzed using the Illumina Infinium Human Methylation BeadChip 450K. After quality control, a total of 256,864 CpG sites were analyzed for their association with prenatal PM10, PM2.5, NO2, and SO2 exposure in the first, second, and third trimesters of pregnancy, respectively. CpG sites associated with prenatal air pollution exposure were studied in relation to ADHD rating scale (ARS) scores at ages 6 and 8. We aimed to investigate the epigenetic effects on the association between prenatal air pollution exposure and ADHD symptoms in children. RESULTS:DNA methylation levels at the 6 CpG sites at age 2 were associated with prenatal SO2 exposure levels at the third trimester: CpG sites located in GP1BB, ATP2C2, GNB4, GRIA1, RPE, INPP5D. Among these, 1 IQR increase in the methylation of cg14130977 (GP1BB) and cg16698748 (ATP2C2) at age 2 was associated with a 0.11 (95% confidence interval (CI) 0.41, 0.83) and 0.12 (95% CI 0.3, 0.76) increase in ARS at age 6, respectively. cg21656520 (RPE) and cg22331159 (INPP5D) showed similar results. CONCLUSIONS:Changes in DNA methylation levels at the CpG sites associated with prenatal SO2 exposure led to increases in ARS scores, suggesting that epigenetic mechanisms underly the effects of prenatal exposure to air pollution on ADHD symptoms in children. KEYWORDS: prenatal, sulfur dioxide, SO2, DNA methylation, ADHD, epigenome-wide association study, epigenetics

Monitoring medication response in ADHD: what can continuous performance tests tell us?

Documenting effectiveness of ADHD medication is essential throughout the course of treatment. A rating scale and a continuous performance test (CPT) with motion tracking were used to study the effect of ADHD medication including compliance during one year. Children (N = 78, age 6–18 years) with ADHD were tested with the QbTest at baseline, visit 1 (1 month after baseline) and visit 5 (12 months after baseline). The ADHD-Rating scale was rated by investigator interview at the same visits. QbTest results and ADHD-RS ratings showed reductions in symptoms on all cardinal parameters of the QbTest and on all ADHD-RS subscales between baseline and 1 month and between baseline and 12 months. There was a weak but significant correlation between the total change scores on the two measures from baseline to 1 month. Eighteen participants dropped out of the study before visit 5; at baseline, these children showed significantly lower results on the inattention parameter of the QbTest, with faster reaction time and lower variation in reaction time, suggesting they suffered less problems with inattention. Both the QbTest and the ADHD-RS showed robust ADHD symptom improvements indicative of medication effect, and the QbTest results might also predict non-compliance of medication. Further research is warranted to increase knowledge about reliable monitoring of long-term medication and compliance.

ADHD and Academic Success in University Students: The Important Role of Impaired Attention

Objective To improve on several methodological issues regarding current literature investigating the relationship between ADHD symptomatology and academic success in adults and examine the relative contributions of specific dimensions of ADHD symptomatology (i.e., inattention, hyperactivity, and impulsivity) to post-secondary academic success. Method A large sample of 3,688 post-secondary students were examined using a longitudinal design. The Conners’ Adult ADHD Rating Scale (CAARS) was used to assess adult ADHD symptoms and academic success was assessed using students’ official academic records (e.g., final GPAs and degree completion status). Results Students with greater inattention symptomatology at the start of their academic program showed consistently poorer long-term academic success (i.e., lower GPAs, higher dropout rates), regardless of gender. Conclusion Inattention symptoms are the primary driver of the relationship between ADHD symptomatology and academic underachievement in adults. Post-secondary education institutions should target and prioritize educational programming for inattention symptoms of ADHD in at-risk post-secondary students.

Neurobiological Basis of Reinforcement-Based Decision-Making in Adults With ADHD Treated With Lisdexamfetamine Dimesylate

Background: The objective of this study was to examine changes in the activation of the brain reward system following treatment with lisdexamfetamine (LDX) vs. placebo (PL) as a function of clinical improvement in attention deficit/hyperactivity disorder (ADHD) symptoms. Methods: Twenty adults with ADHD were included in a randomized cross-over study. Participants underwent two functional magnetic resonance imaging (fMRI) scans, after receiving 3 to 5 weeks of treatment with both LDX and PL. During scanning, participants performed the passive-avoidance learning task to assess reward-related learning using computational variables (e.g., estimated value and prediction error). Pre-treatment to post-treatment symptom change was assessed via the ADHD Rating Scale (ADHD-RS). The imaging contrasts were Object Choose or Object Refuse during the object choice component of the task, modulated by expected value (reward vs. nonreward cue), and Reward vs. Punishment during feedback, modulated by prediction error (expected vs. actual outcome). To address the primary objective, we performed group-level mass univariate analyses between pre-treatment to post-treatment percent change of the ADHD-RS total scores and the four contrast images under the choice and feedback conditions, with significance set at a whole-brain voxel-wise threshold of p < .05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. Results: Improvement in ADHD symptoms was accompanied by significant increases of brain activation during the Object Refuse, Reward and Punishment contrasts in a widespread network including left caudate and putamen, and right orbitofrontal cortex (i.e., reward-related signaling) and left middle frontal, superior frontal, and precentral gyri (i.e., executive control). Conclusions: These findings are the first to show that the increase in responsiveness of systems engaged in reward processing with LDX treatment is positively related to symptom improvement. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.

A novel approach to diagnose ADHD using virtual reality

PurposeThe current golden standard for attention deficit hyperactivity disorder (ADHD) diagnosis is clinical diagnosis based on psychiatric interviews and psychological examinations. This is suboptimal, as clinicians are unable to view potential patients in multiple natural settings – a necessary condition for objective diagnosis. The purpose of this paper is to improve the objective diagnosis of ADHD by analyzing a quantified representation of the actions of potential patients in multiple natural environments.Design/methodology/approachThe authors use both virtual reality (VR) and artificial intelligence (AI) to create an objective ADHD diagnostic test. Diagnostic and statistical manual of mental disorders, 5th Edition (DSM-5) and ADHD Rating Scale are used to create a rule-based system of quantifiable VR-observable actions. As a potential patient completes tasks within multiple VR scenes, certain actions trigger an increase in the severity measure of the corresponding ADHD symptom. The resulting severity measures are input to an AI model, which classifies the potential patient as having ADHD in the form inattention, hyperactivity-impulsivity, combined or neither.FindingsThe result of this study shows that VR-observed actions can be extracted as quantified data, and classification of this quantified data achieves near-perfect sensitivity and specificity with a 98.3% accuracy rate on a convolutional neural network model.Originality/valueTo the best of the authors’ knowledge, this is the first study to incorporate VR and AI into an objective DSM-5-based ADHD diagnostic test. By including stimulation to the visual, auditory and equilibrium senses and tracking movement and recording voice, we present a method to further the research of objective ADHD diagnosis.

Long-term medication for ADHD and development of cognitive functions in children and adolescents

ObjectiveLong-term effects of ADHD medication on cognitive functions are not well known. This study investigates development of cognitive functions and ADHD symptoms on well-controlled medication for 1 year in children and adolescents. Study designThis study is part of an ongoing open uncontrolled trial of long-term medication for ADHD in children and adolescents aged 6–18 years with any form of ADHD, and frequently comorbid autism spectrum disorder (ASD, 29%) or autistic traits (24%). Other comorbidities were oppositional defiant disorder, dyslexia/language disorder, borderline intellectual functioning, developmental coordination disorder. This analysis includes 87 participants (61 boys, 26 girls) who completed Wechsler tests at baseline and after 12 months. ADHD symptoms were investigator-rated on the ADHD Rating Scale-IV at the same time points. ResultsThe whole group of children and adolescents showed significant improvements in Wechsler Full Scale IQ (FSIQ, mean at baseline 92.6, at 12 months 97.95), and on the Index Scales Verbal Comprehension, Working Memory and Processing Speed, after one year of well-controlled ADHD medication. Comorbid dyslexia/language impairment predicted a larger rise in FSIQ, but not gender, ADHD presentation or comorbid ASD. Robust improvements in ADHD symptoms were observed (mean ADHD-Rating Scale score at baseline 34.6, and at 12 months 18.3). ConclusionsCognitive test scores and ADHD symptoms were improved on well-controlled medication for 1 year in children and adolescents with ADHD, autism and other comorbidities. The main study limitation is the open uncontrolled trial design.

Stimulant Treatment Effect on Anxiety Domains in Children with Attention-Deficit/Hyperactivity Disorder With and Without Anxiety Disorders: A 12-Week Open-Label Prospective Study.

Objectives: The effect of stimulants on anxiety domains has not been systematically studied. We assessed prospectively the impact of stimulant treatment in children with attention-deficit/hyperactivity disorder (ADHD) on the severity of anxiety domains and on ADHD with comorbid anxiety disorders. Methods: Children with ADHD (n = 57, aged 6-15 years) started a stimulant or were switched from one stimulant to another. Assessments were conducted at four time points (baseline and weeks 2, 6, and 12) and consisted of parental questionnaires (ADHD rating scale, screen for child anxiety related disorders [SCARED]), and side effect questionnaire completed by a child psychiatrist. Results: A significant improvement in total SCARED scores was obtained after 12 weeks stimulant treatment in children both with and without anxiety disorders. Significant reductions were detected in generalized anxiety, separation anxiety, and school avoidance SCARED subscales, but not in panic and social anxiety subscales. ADHD symptoms significantly improved both in children with and without anxiety comorbidities. Conclusion: We found specific effects of stimulants on anxiety domains. Stimulant treatment, even for ADHD children diagnosed with comorbid anxiety disorders, is relatively safe regarding the risk of anxiety exacerbation. Moreover, the presence of anxiety symptoms or disorders does not interfere with the beneficial effect of the stimulants on the ADHD core symptoms. Clinical trial regestration number: IRB SMC-6893-20.

Effect of Iron Supplementation in Children with Attention-Deficit/Hyperactivity Disorder and Iron Deficiency: A Randomized Controlled Trial.

To determine the effectiveness of combined iron supplementation and methylphenidate treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children/adolescents with ADHD and iron deficiency compared with methylphenidate alone. In total, 116 children/adolescents with ADHD were screened for iron deficiency. Participants who exhibited iron deficiency were randomized into 2 groups (ferrous supplementation vs placebo). Vanderbilt ADHD rating scales were completed by parents and teachers at prestudy and poststudy periods. Student's t tests were used to determine improvements of Vanderbilt scores between the groups. Among 116 children who participated in this study, 44.8% (52/116) met the criteria for iron deficiency. Of the total 52 participants with iron deficiency, 26 were randomized to the ferrous group and 26 to the placebo group. Most participants in each group had been prescribed short-acting methylphenidate twice daily in the morning and at noon. After a 12-week study period, total parents' Vanderbilt ADHD symptom scores showed a significant improvement between the groups (mean decrement = -3.96 ± 6.79 vs 0 ± 6.54, p = 0.037). However, teachers' Vanderbilt ADHD symptom scores showed no difference between the groups. Children with ADHD and iron deficiency being on methylphenidate and iron supplementation had shown improvement of ADHD symptoms that were reported by parents.

Study of the Interaction between Executive Function and Adaptive Behavior at School in Girls with Fragile X Syndrome.

The aim of this research is to analyze the relationship between executive functions and adaptive behavior in girls with Fragile X syndrome (FXS) in the school setting. This study is part of a larger investigation conducted at the Hospital Parc Tauli in Sabadell. The sample consists of a total of 40 girls (26 with FXS and 14 control) aged 7–16 years, who were administered different neuropsychological tests (WISC-V, NEPSY-II, WCST, TOL) and questionnaires answered by teachers (ABAS-II, BRIEF 2, ADHD Rating Scale). The results show that there is a greater interaction between some areas of executive function (cognitive flexibility, auditory attention, and visual abstraction capacity) and certain areas of adaptive behavior (conceptual, practical, social, and total domains) in the FXS group than in the control group. These results suggest that an alteration in the executive functions was affecting the daily functioning of the girls with FXS to a greater extent.

A Placebo-Controlled Trial of Lisdexamfetamine in the Treatment of Comorbid Sluggish Cognitive Tempo and Adult ADHD.

Objective: To examine the efficacy of lisdexamfetamine (LDX) versus placebo on behavioral attributes of sluggish cognitive tempo (SCT) in adults with attention-deficit/hyperactivity disorder (ADHD) and SCT. Methods: In a randomized crossover trial conducted January 2016–April 2018, 38 adults with DSM-5 ADHD (via the Adult ADHD Clinical Diagnostic Scale v1.2) and SCT were recruited at 2 academic medical centers and assessed for symptoms of ADHD, SCT, executive function deficits, and functional impairment at baseline and weekly during treatment. Participants received 4 weeks of treatment with either LDX (30–70 mg/d; mean = 59.1 ± 14.8 mg/d) or matching placebo (mean = 66.6 ± 9.1 mg/d) with a 2-week washout before switching to the other arm. The ADHD Rating Scale and Barkley Adult ADHD Rating Scale-IV SCT subscale were coprimary outcome measures. Results: There were moderately large treatment effects of LDX vs placebo on SCT ratings in both treatment periods (block 1 effect size = 0.68; block 2 effect size = 0.61), which reached significance only in block 1 owing to carryover effects of the first treatment epoch into the second. Significant effects were also seen for LDX over placebo in ADHD, executive function deficit, and functional impairment ratings, without order effects; no site differences were seen except on the Global Executive Complex score of the Behavior Rating Inventory of Executive Function—Adult Version. No moderating effects of sex, age, race, and ethnicity were seen. Conclusions: Adults with ADHD and comorbid SCT had significant improvement after LDX vs placebo in ratings of SCT, ADHD, executive function deficits, and functional impairment. This is the first study to show improvement in SCT after stimulant therapy in adults with ADHD. Trial Registration: ClinicalTrials.gov identifier: NCT02635035

Clinical and neuropsychological characteristics of children with epilepsy and attention-deficit/hyperactivity disorder

ObjectivesThis study aimed to explore the clinical and neuropsychological characteristics—cognition, behavior, parenting-related stress, and sleep—of children with epilepsy, attention-deficit/hyperactivity disorder (ADHD), or both. MethodsWe retrospectively reviewed the electronic medical records of 33 children with epilepsy and ADHD, 113 with epilepsy alone, and 294 with ADHD alone. The children were required to complete the Advanced Test of Attention (ATA), and their parents completed the ADHD Rating Scale (ARS), Child Behavior Checklist (CBCL), Children's Sleep Habits Questionnaire (CSHQ), Disruptive Behavior Disorder (DBD) Scale (DBD), Social Responsiveness Scale (SRS), and Parenting Stress Index-Short Form (PSI-SF). ResultsAuditory Commission Errors made during the ATA were higher in children with epilepsy and ADHD than in those with epilepsy alone. On the SRS, all the subscales except Social Awareness were significantly higher in children with epilepsy and ADHD or ADHD alone than in those with epilepsy alone. The Oppositional Defiant and Conduct Disorder subscales on DBD, Attention Problems, and Aggressive Behaviors on CBCL were significantly higher in children with both epilepsy and ADHD than in those with epilepsy alone. The Parent-Child Dysfunctional Interaction subscales on the PSI-SF were significantly greater in children with both epilepsy and ADHD than in those with epilepsy alone. The subscales on the CSHQ did not significantly differ between children with both epilepsy and ADHD and those with epilepsy alone. ConclusionsIn children with epilepsy, comorbid ADHD was associated with negative effects on response inhibition, aggressive behavior, and parenting-related stress.

Adult ADHD, executive function, depressive/anxiety symptoms, and quality of life: A serial two-mediator model

BackgroundAdult attention-deficit/hyperactivity disorder (ADHD) is associated with impaired executive function (EF), depressive/anxiety symptoms, and poor quality of life (QoL). In this study, we aimed to investigate correlations among these variables and to build a simple or serial mediation model for exploring the mechanisms between adult ADHD and QoL. MethodsThis was a cross-sectional study. The sample included 223 participants with ADHD and 54 healthy volunteers. Participants were required to complete the following scales: ADHD Rating Scale (ADHD-RS), Brief Version of the World Health Organization Quality of Life Scale (WHOQOL-BREF), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). Correlations among EF, depressive/anxiety symptoms and QoL were analyzed using Pearson correlation. The simple and serial mediation models were analyzed using PROCESS (version 3.3). ResultsThe correlations between EF and QoL, depressive/anxiety symptoms and QoL, and depressive/anxiety symptoms and EF were statistically significant. In ADHD adults with comorbidities, the correlation coefficients were between -0.19 and -0.47, -0.20 and -0.62, 0.28 and 0.50, respectively. In simple mediation models, EF and depressive/anxiety symptoms were significant mediators respectively between ADHD and QoL, respectively. In a serial two-mediator model, ADHD could affect QoL indirectly via EF and then via depressive/anxiety symptoms significantly. LimitationsThe average age was young, the degree of education was high, and only self-reported scales were relied on. ConclusionsThere is a mutual effect between EF and emotional symptoms. This was the first study to build a serial two-mediator model between ADHD and QoL, suggesting the importance of EF and depressive/anxiety symptoms.

Efficacy and Safety of Medication for Attention-Deficit Hyperactivity Disorder in Children and Adolescents with Common Comorbidities: A Systematic Review.

IntroductionComorbid psychiatric conditions in children and adolescents with attention-deficit hyperactivity disorder (ADHD) occur frequently, complicate management, and are associated with substantial burden on patients and caregivers. Very few systematic reviews have assessed the efficacy and safety of medications for ADHD in children and adolescents with comorbidities. Of those that were conducted, most focused on a particular comorbidity or medication. In this systematic literature review, we summarize the efficacy and safety of treatments for children and adolescents with ADHD and comorbid autism spectrum disorders, oppositional defiant disorder, Tourette’s disorder and other tic disorders, generalized anxiety disorder, and major depressive disorder.MethodsWe searched MEDLINE, Embase, and ClinicalTrials.gov (to October 2019) for studies of patients (aged < 18 years) with an ADHD diagnosis and the specified comorbidities treated with amphetamines, methylphenidate and derivatives, atomoxetine (ATX), and guanfacine extended-release (GXR). For efficacy, placebo-controlled randomized controlled trials (RCTs) or meta-analyses of RCTs were eligible for inclusion; for safety, all study types were eligible. The primary efficacy outcome measure was ADHD Rating Scale IV (ADHD-RS-IV) total score.ResultsOf 2177 publications/trials retrieved, 69 were included in this systematic literature review (5 meta-analyses, 37 placebo-controlled RCTs, 16 cohort studies, 11 case reports). A systematic narrative synthesis is provided because insufficient data were retrieved to combine ADHD-RS-IV total scores or effect sizes. Effect sizes for ADHD-RS-IV total scores were available for ten RCTs and ranged from 0.46 to 1.0 for ATX and from 0.92 to 2.0 for GXR across comorbidities. The numbers and types of adverse events in children with comorbidities were consistent with those in children without comorbidities, but treatment should be individualized to ensure children can tolerate the lowest effective dose.ConclusionLimited information is available from placebo-controlled RCTs on the efficacy (by ADHD-RS-IV) or safety of medication in children with ADHD and psychiatric comorbidities. Further studies are required to support evidence-based drug selection for these populations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00249-0.

Current use of attention-deficit hyperactivity disorder (ADHD) medications and clinical characteristics of child and adolescent psychiatric outpatients prescribed multiple ADHD medications in Japan.

Patients with attention-deficit hyperactivity disorder (ADHD) manifest symptoms of hyperactivity, impulsivity, and/or inattention. ADHD medications available in Japan are limited compared with those in Western countries. Prescribing status has not been sufficiently evaluated in clinical settings in Japan. This study investigated the current use of ADHD medications and characteristics of patients who received multiple ADHD medications in a clinical setting in Japan. Study participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital between April 2015 and March 2020. We investigated patients who received osmotic-controlled release oral delivery system methylphenidate, atomoxetine, or guanfacine. A retrospective case-control design was used to evaluate the characteristics of patients who received multiple ADHD medications. Patients who were given three ADHD medications were defined as the case group. Randomly sampled sex- and age-matched patients diagnosed with ADHD were defined as the control group. We compared data for child-to-parent violence, antisocial behavior, suicide attempt or self-harm, abuse history, refusal to attend school, and two psychological rating scales (the ADHD-Rating Scale and Tokyo Autistic Behavior Scale). Among the 878 patients who were prescribed any ADHD medications, 43 (4.9%) received three ADHD medications. Logistic regression revealed that children with severe ADHD symptoms, autistic characteristics, or tendency of child-to-parent violence were more likely to have been prescribed three medications during their treatment. Our findings suggest the approach to prevent the use of multiple ADHD medications. A prospective study to investigate the causality between prescribing status and clinical characteristics is warranted.

The Effect of Viloxazine Extended-Release Capsules on Functional Impairments Associated with Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents in Four Phase 3 Placebo-Controlled Trials.

PurposeThe ADHD Rating Scale (ADHD-RS) assesses 18 symptoms of inattention and hyperactivity/impulsivity and has been used in many clinical trials to evaluate the treatment effect of drugs on ADHD. The fifth edition of this scale (ADHD-RS-5) also assesses the impact of inattention and hyperactivity/impulsivity symptoms on six domains of functional impairment (FI): family relationships, peer relationships, completing/returning homework, academic performance at school, controlling behavior at school, and self-esteem. Here, we report the effect of viloxazine extended-release capsules (viloxazine ER), a novel nonstimulant treatment for ADHD in children and adolescents (ages 6–17 years), on FI from a post hoc analysis of four randomized, double-blind, placebo-controlled Phase 3 clinical trials (N=1354).Patients and MethodsADHD-RS-5 investigator ratings of ADHD symptoms and FIs were conducted at baseline and weekly post-baseline for 6–8 weeks in the four trials. Change from baseline (CFB) in ADHD-RS-5 FI scores (Total score [sum of 12 FI items] and Inattention and Hyperactivity/Impulsivity subscale scores [sum of 6 corresponding FI items]) and the 30% and 50% Responder Rates (ADHD-RS-5 FI Total score) were compared between viloxazine ER and placebo.ResultsThe reduction (improvement) in ADHD-RS-5 FI scores (Total and subscale scores) and the percentage of responders (30% and 50%) at Week 6 were significantly greater in each viloxazine ER dose group vs placebo. In the 100–400 mg/day viloxazine ER groups, improvements were found as early as Week 1 (100-mg/day) or Week 2 (200-, 400-mg/day) of treatment. Analysis of individual items of ADHD-related FIs demonstrated that the effect of viloxazine ER was observed across all domains of impairment.ConclusionSignificant improvements observed in ADHD-related FIs are consistent with the reduction in inattention and hyperactivity/impulsivity symptoms demonstrated in the viloxazine ER Phase 3 pediatric trials. Therefore, viloxazine ER provides clinically meaningful improvement of ADHD symptoms and functioning in children and adolescents with ADHD, starting as early as Week 1–2 of treatment.

FDA Approves Qelbree for ADHD

Back to table of contents Previous article Next article Clinical & ResearchFull AccessFDA Approves Qelbree for ADHDTerri D'ArrigoTerri D'ArrigoSearch for more papers by this authorPublished Online:20 May 2021https://doi.org/10.1176/appi.pn.2021.6.12AbstractViloxazine is not a stimulant and is not a controlled substance.In April the Food and Drug Administration (FDA) approved Qelbree (viloxazine extended-release capsules), a selective norepinephrine reuptake inhibitor, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients aged 6 to 17 years. Qelbree is not a stimulant and is not a controlled substance.In three separate phase 3 trials involving 1,118 patients aged 6 to 17 years, patients who took Qelbree experienced a greater improvement in ADHD symptoms compared with those who took placebo, as measured by the ADHD Rating Scale and the Clinical Global Impression-Improvement score. Doses during the trials ranged from 100 mg to 400 mg.The recommended starting dose for patients 6 to 11 years old is 100 mg once daily. The recommended starting dose for patients 12 to 17 years old is 200 mg once daily. Dosages for both age groups may be titrated up to 400 mg once daily. Qelbree is taken once daily, and capsules may be broken open and sprinkled on applesauce or swallowed whole.Qelbree may be an option for patients with a history of substance use for whom there may be a concern about using controlled substances like stimulants, says David Rettew, M.D.Valerie HarderDavid Rettew, M.D., the medical director of the Child and Adolescent and Families Division of the Vermont Department of Mental Health and an associate professor of psychiatry and pediatrics at the University of Vermont, said he sees where Qelbree may provide a new treatment option for several patient populations.“One would be the child or adolescent who can’t take stimulant medications due to side effects,” Rettew told Psychiatric News. “Since Qelbree doesn’t have the on/off quality of stimulants where the benefits wear off during the day, there also could be interest in patients and families looking for a more even effect throughout the day. Finally, its use might be considered in individuals with substance use histories where there could be concern about using controlled substances like stimulants.”Qelbree’s label contains a boxed warning that the medication may increase the risk of suicidal thoughts and behaviors. The warning advises health professionals who prescribe Qelbree to monitor patients closely for “clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes.”Data from the clinical trials also suggest that the medication may induce manic or mixed episodes in patients with bipolar disorder, and the label cautions that patients should be screened to determine if they are at risk for bipolar disorder.Between 22% and 31% of patients who received Qelbree in the clinical trials experienced an increase in heart rate of at least 20 beats a minute and a 15-point increase in their diastolic blood pressure. The label advises that health professionals should assess their patients’ heart rate and blood pressure prior to initiating treatment and when increasing dosages. However, this may be easier said than done during the pandemic.“Right now, so many medical appointments are being done via telemedicine, and vital signs are more difficult to get,” said Rettew. Rettew noted that viloxazine was marketed as an antidepressant in other countries before being marketed as a treatment for ADHD in the United States.“[Qelbree] therefore has many of the same warnings [as antidepressants], such as the potential for increased suicidal thoughts and activation of mania. Some of the blood pressure and pulse increases have also been found with antidepressants that have norepinephrine reuptake properties such as venlafaxine,” he said. “While the medication is touted as working as a norepinephrine reuptake blocker, there is some research suggesting that it also acts on serotonin, similar to many other antidepressants.”Rettew said he will keep an open mind about Qelbree, but that it would not surprise him if it is seen as similar to another nonstimulant medication for ADHD, Strattera (atomoxetine).“[Strattera] is often pretty well tolerated but there have been some data suggesting that it may not result in as much improvement in core ADHD symptoms as the stimulants. From some of the data from initial trials, it looks like Qelbree could be in the same boat,” Rettew said.“It is also worth noting that all of the ADHD trials [for Qelbree] have been short, just a matter of weeks. Long-term data are really needed, although we do have a long track record of [viloxazine’s] use as an antidepressant.”Rettew is not affiliated with Supernus Pharmaceuticals and was not involved in clinical trials of Qelbree. ■Full prescribing information for Qelbree is posted here. ISSUES NewArchived

The Relationship between Plasma Erythropoietin Levels and Symptoms of Attention Deficit Hyperactivity Disorder.

ObjectiveThere are animal models associating dopamine dysfunction with behavioral impairments that model attention deficit hyperactivity disorder (ADHD). Erythropoietin (EPO) has trophic effects on dopaminergic neurons. The aim of this study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD.MethodsPlasma EPO levels were measured in 78 drug-naïve children with ADHD and in 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in ADHD children and healthy controls.ResultsThe difference between median plasma EPO levels in ADHD children and in healthy controls was not statistically significant. Adjusting for age and sex, a linear regression analysis showed that inattention score was significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Hyperactivity-impulsivity score was significantly higher in the highest tertile of plasma EPO compared to those in the lowest tertile. Moreover, total K-ARS scores were significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile.ConclusionThese findings suggest that plasma EPO levels were related to some ADHD symptoms, which could be used in the monitoring of the disorder.

How much impairment is required for ADHD? No evidence of a discrete threshold.

A diagnosis of attention-deficit/hyperactivity disorder (ADHD) requires the presence of impairment alongside symptoms above a specific frequency and severity threshold. However, the question of whether that symptom threshold represents anything more than an arbitrary cutoff on a continuum of impairment requires further empirical study. Therefore, we present the first study investigating if the relationship between ADHD symptom severity and functional impairment is nonlinear in a way that suggests a discrete, nonarbitrary symptom level threshold associated with a marked step increase in impairment. Parent reports on the ADHD-Rating Scale (ADHD-RS-IV), the Weiss Functional Impairment Rating Scale (WFIRS-P), and the Strengths and Difficulties Questionnaire were collected in a general population sample of 1st, 2nd, and 3rd graders (N = 1,914-2,044). Piecewise linear regression analyses and nonlinear regression modeling both demonstrated that the relationship between symptom severity (ADHD-RS-IV total score) and impairment (WFIRS-P mean score) was characterized by a gradual linear increase in impairment with higher symptom severity and no apparent step increase or changing rate of increase in impairment at a certain high ADHD-RS-IV total score level. Controlling for socioeconomic status, sex, and co-occurring conduct and emotional symptoms did not alter these results, though comorbid symptoms had a significant effect on impairment. There was no clear evidence for a discrete, nonarbitrary symptom severity threshold with regard to impairment. The results highlight the continued need to consider both symptoms and impairment in the diagnosis of ADHD.

Pilot study of socio-emotional factors and adaptive behavior in young females with fragile X syndrome

ABSTRACT Girls with Fragile-X-Syndrome (FXS) present high levels of social anxiety, social avoidance, extreme shyness, tendency to social isolation, poor eye contact, learning difficulties, and depression. The aims of the present study, which is based on a group of young females with FXS are: 1) to analyze the possible associations between emotion recognition, theory of mind, and social anxiety, and adaptive behavior, and emotional state; 2) to study the relationship between intelligence quotient (IQ) and adaptive behavior; and 3) to assess whether social anxiety is more prevalent in girls with FXS. The study has 40 female participants aged between 7 and 16 years (26 positive full mutation FXS and 14 as a control group). A neuropsychological assessment was conducted using the following tests: WISC-V, NEPSY-II, SENA, ADHD Rating Scale, BAS, and ABAS-II. In comparison with the control group, the group with FXS presented a greater association between IQ and self-direction ability, and between emotion recognition and leadership. The FXS group presented higher levels of social anxiety and shyness. In the group of girls with FXS, IQ may have prognostic value for both self-direction ability and social adaptation level.

Mood and Proneness to Boredom Are Associated with Poorer Continuous Performance Test Results, Which May Improve with Methylphenidate Treatment, in Attention-Deficit/Hyperactivity Disorder

Objectives: This study aimed to evaluate the relationship between baseline test of variables of attention (TOVA) performance, attention-deficit/hyperactivity disorder (ADHD) symptom severity, mood symptoms, proneness to boredom in children with ADHD, and to assess the responses of the various scales to methylphenidate treatment. Methods: Thirty-three children and adolescents with ADHD, aged 7-18 years, were assessed at baseline with TOVA and treated for 3 months thereafter with methylphenidate. The ADHD Rating Scale (ADHD-RS), Short Boredom Proneness Scale (SBPS), Children's Depression Inventory (CDI) scale, and CDI-academic and social subscale (CDI-AS) were administered to all participants at baseline and after 3 months of methylphenidate (MPH) treatment. Results: The baseline TOVA reaction time (RT) and RT variability parameters correlated with baseline SBPS and CDI-AS scores as well as with baseline total CDI scores. Significant improvements were found in ADHD-RS, SBPS, and CDI-AS scores after MPH treatment. The alteration in ADHD-RS correlated with parallel changes in SBPS and CDI-AS scores. Conclusions: Mood and proneness to boredom correlate with poor attention-span in children with ADHD. Improvement in ADHD levels after MPH treatment correlates with a parallel decrease in mood symptoms related to academic achievement and social functioning.