Health care resource utilization and costs associated with psychiatric comorbidities in adult patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition with extensive psychiatric comorbidities. ADHD has been associated with substantial clinical and economic burden; however, little is known about the incremental burden specifically attributable to psychiatric comorbidities of ADHD in adults. OBJECTIVE: To assess the impact of psychiatric comorbidities, specifically anxiety and depression, on health care resource utilization (HRU) and costs in treated adults with ADHD in the United States. METHODS: A retrospective case-cohort study was conducted. Adults with ADHD were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was defined as the date of initiation of a randomly selected ADHD treatment. The baseline period was defined as the 6 months prior to the index date, and the study period as the 12 months following the index date. Patients with at least 1 diagnosis for anxiety and/or depression during both the baseline and study periods were classified in the ADHD+anxiety/depression cohort, whereas those without diagnoses for anxiety or depression at any time were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts with similar baseline characteristics. All-cause HRU and health care costs were assessed during the study period and compared between cohorts using regression analyses. Cost analyses were also conducted in subgroups stratified by comorbid conditions. RESULTS: After reweighting, patients in the ADHD-only cohort (N = 276,906) and ADHD+anxiety/depression cohort (N = 217,944) had similar characteristics (mean age 34.1 years; 54.8% male). All-cause HRU was higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 4.5, emergency department visits: 1.8, outpatient visits: 2.0, and psychotherapy visits: 6.4; all P < 0.01). All-cause health care costs were more than 2 times higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (mean per-patient per-year [PPPY] costs in ADHD-only vs ADHD+anxiety/depression cohort: $5,335 vs $11,315; P < 0.01). Among the ADHD+anxiety/depression cohort, average all-cause health care costs were $9,233, $10,651, and $15,610 PPPY among subgroup of patients with ADHD and only anxiety, only depression, and both anxiety and depression, respectively. CONCLUSIONS: Comorbid anxiety and depression is associated with additional HRU and costs burden in patients with ADHD. Comanagement of these conditions is important and has the potential to alleviate the burden experienced by patients and the health care system.

Barriers and facilitators to implementing a Canadian shared-care ADHD program in pediatric settings in Shanghai: a consolidated framework for implementation research approach.

OBJECTIVES: The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region. METHODS: Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals. Two independent researchers conducted a thematic analysis of the data with themes emerging based on the Consolidated Framework for Implementation Research (CFIR). RESULTS: Notable barriers identified by participants included: (1) lack of knowledge in the management of ADHD, primarily among general practitioners; (2) lack of resources such as lack of staff, time, and medication for ADHD; (3) challenges in implementing an international multicentre intervention (such as communication difficulties between teams and integration of resources available in different hospitals); and (4) mental health stigma, difficulties in identifying ADHD patients, and logistical problems related to medication procurement rules put in place by provincial governments. Notable facilitators included: (1) the strong motivation of stakeholders and their confidence in their ability to learn and subsequently execute action plans to achieve the implementation goal; (2) the compatibility between the values and goals of the stakeholders and those of the program despite some cultural tension, a positive learning climate, strong tensions for change, and the high interest of organization leaders in engaging in the program (3) the perceived benefits of the program, such as standardization of the diagnostic and treatment process, and engaging primary care providers in ADHD management; and (4) the strong relationship between participating institutions and schools as well as provincial health initiatives available to support collaborative models of care. Mixed factors to implementation were also explored. CONCLUSIONS: Appropriate training of health care providers, cultural adaptation of the program, increase public awareness about ADHD to decrease stigma, as well as strong project management and guidelines that clearly describe the role and expectations of each team member appeared essential to successful implementation.

Neurocognitive training enhances the outcomes of children with attention deficit hyperactivity disorder: A preliminary study.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by diverse clinical manifestations including inattention, hyperactivity and impulsivity. OBJECTIVE: The present study aims to investigate the effects of neurocognitive training (NT), a personalized and specialized exercise programme on symptoms, attention and dynamic balance in treatment-naïve children diagnosed with ADHD. METHODS: Fourteen treatment-naïve children aged 7-12 years diagnosed with ADHD were enrolled in the intervention group. The NT intervention was administered weekly for 10 consecutive weeks, supplemented by a structured home exercise programme for 6 days a week over the same 10-week period. ADHD-related symptoms, attention and dynamic balance were assessed in pre-treatment, post-treatment, 6 months, and 12 months. Fifteen typically developing (TD) children, matched for age, underwent evaluation only once to establish baseline normative values. RESULTS: Following the NT (post-treatment), significant improvements were observed in hyperactivity-impulsivity scores, oppositional-defiant behaviours and dynamic balance when compared to the TD children (p < 0.05). In the ADHD group, a significant difference was found in the long term (12-month follow-up) in hyperactivity-impulsivity, oppositional-defiant behaviours and dynamic balance (p < 0.05). CONCLUSION: The findings suggest that the NT yields favourable effects on hyperactivity-impulsivity, oppositional defiant behaviours and dynamic balance in children diagnosed with ADHD, with these improvements appearing to be sustained over the long term. CLINICAL TRIAL REGISTRATION NUMBER: NCT04707040.

The management of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD): an update of the literature.

INTRODUCTION: Sleep disorders represent an important comorbidity in individuals with ADHD. While the links between ADHD and sleep disturbances have been extensively investigated, research on the management of sleep disorders in individuals with ADHD is relatively limited, albeit expanding. AREAS COVERED: The authors searched PubMed, Medline, PsycInfo, Embase+Embase Classic, Web of Sciences databases, and clinicaltrials.gov up to 4 January 2024, for randomized controlled trials (RCTs) of any intervention for sleep disorders associated with ADHD. They retained 16 RCTs (eight on pharmacological and eight on non-pharmacological interventions), supporting behavioral intervention and melatonin, and nine ongoing RCTs registered on clinicaltrials.gov. EXPERT OPINION: The pool of RCTs testing interventions for sleep disorders in individuals with ADHD is expanding. However, to inform clinical guidelines, there is a need for additional research in several areas, including 1) RCTs based on a precise phenotyping of sleep disorders; 2) pragmatic RCTs recruiting neurodevelopmental populations representative of those seen in clinical services; 3) trials testing alternative interventions (e.g. suvorexant or light therapy) or ways to deliver them (e.g. online); 4) sequential and longer-term RCTs; 5) studies testing the impact of sleep interventions on outcomes other than sleep; 6) and implementation of advanced evidence synthesis and precision medicine approaches.

Evolving Adult ADHD Care: Preparatory Evaluation of a Prototype Digital Service Model Innovation for ADHD Care.

BACKGROUND: Given the prevalence of ADHD and the gaps in ADHD care in Australia, this study investigates the critical barriers and driving forces for innovation. It does so by conducting a preparatory evaluation of an ADHD prototype digital service innovation designed to help streamline ADHD care and empower individual self-management. METHODS: Semi-structured interviews with ADHD care consumers/participants and practitioners explored their experiences and provided feedback on a mobile self-monitoring app and related service innovations. Interview transcripts were double coded to explore thematic barriers and the enablers for better ADHD care. RESULTS: Fifteen interviews (9 consumers, 6 practitioners) revealed barriers to better ADHD care for consumers (ignorance and prejudice, trust, impatience) and for practitioners (complexity, sustainability). Enablers for consumers included validation/empowerment, privacy, and security frameworks, tailoring, and access. Practitioners highlighted the value of transparency, privacy and security frameworks, streamlined content, connected care between services, and the tailoring of broader metrics. CONCLUSIONS: A consumer-centred approach to digital health service innovation, featuring streamlined, private, and secure solutions with enhanced mobile tools proves instrumental in bridging gaps in ADHD care in Australia. These innovations should help to address the gaps in ADHD care in Australia. These innovations should encompass integrated care, targeted treatment outcome data, and additional lifestyle support, whilst recognising the tensions between customised functionalities and streamlined displays.

Process evaluation of a Structured E-parenting Support (STEPS) in the OPTIMA randomised controlled trial: a protocol.

INTRODUCTION: Structured E-parenting Support (STEPS) is a digital application (app) designed to help parents manage behaviour of their children who are referred to mental health services and are waiting for an assessment or treatment. STEPS is currently being evaluated in the Online Parent Training for the Initial Management of Attention-Deficit/Hyperactivity Disorder randomised controlled trial. Alongside the examination of STEPS' clinical and cost-effectiveness, we are conducting a process evaluation to better understand the contextual factors that may influence study outcomes. The purpose of this protocol is to describe the aims, objectives and methodology of the process evaluation prior to it taking place to add to the fidelity and rigour of the trial process and outcomes. Our goal is to adapt STEPS to optimise its benefits in future applications. METHODS: In line with the Medical Research Council guidelines for evaluating complex interventions, the process evaluation will adopt a mixed method design using qualitative data collected from clinicians and parent interviews and app usage data from participants assigned to the intervention arm. ANALYSIS: Qualitative data from semistructured interviews and free text box responses included in trial questionnaires will be analysed thematically using framework analysis to better understand how parents use STEPS, how it works and key factors that could aid or hinder its effective implementation in routine clinical practice. ETHICS: The application for ethical approval for the study was submitted to the North West-Liverpool Central Research Ethics Committee and received a favourable opinion on further information on 26 November 2021, reference number 21/NW/0319. DISSEMINATION: The process evaluation aims to explore how a digital app might support parents in managing their child's behaviour. Implications for policy and research will be explored and the clinical implications of offering the app to a wider audience to address the lack of support to parents as highlighted in this paper. We plan to publish findings in international, peer-reviewed journals as well as present at conferences. TRIAL REGISTRATION NUMBER: The trial has been prospectively registered on 18 November 2021; ISRCTN816523503. https://www.isrctn.com/ISRCTN16523503.

A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. OBJECTIVE: The aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. METHODS: This 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. RESULTS: Among the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants' average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (ß=-12.203, 95% CI -17.882 to -6.523; P<.001), owing to lower scores on the subscales Inattention (ß=-3.966, 95% CI -6.285 to -1.647; P<.001), Hyperactivity/Impulsivity (ß=-5.735, 95% CI -8.334 to -3.137; P<.001), and Oppositional Defiant Disorder (ß=-2.995, 95% CI -4.857 to -1.132; P=.002). The intervention was associated with significant reduction in the Metacognition Index (ß=-6.312, 95% CI -10.973 to -1.650; P=.006) and Global Executive Composite (ß=-5.952, 95% CI -10.214 to -1.690; P=.003) on the BRIEF. No severe intervention-related adverse events were reported. CONCLUSIONS: This novel digital cognitive-physical intervention was efficacious in school-age children with ADHD. A larger multicenter effectiveness trial with longer follow-up is warranted to confirm these findings and to assess the durability of treatment effects. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2300070521; https://www.chictr.org.cn/showproj.html?proj=177806.

Attention-deficit Hyperactivity Disorder and Autism Spectrum Disorder: Towards Better Diagnosis and Management.

Background: Attention-deficit hyperactivity disorder (ADHA) is one of the most common comorbid disorders of autism spectrum disorder (ASD) that can accompany autism, triggered by it, or be a consequence of it. Objective: This review explored the prevalence of the comorbidity of both disorders, neurobiological background, symptoms, latest assessment methods, and therapeutic approaches. Results and Discussion: It concluded that effective assessment, diagnosis and management of ADHD in ASD children and adults is essential for this group of patients to thrive and live a good quality of life. Further research is recommended to explore the most effective intervention for such important members of our society. Conclusion: More studies are needed to understand the mechanisms underlying these comorbidities, and to prevent the misdiagnosis and mismanagement of these disorders. Also, to develop up to date personalized therapeutic plans for such children.

Family-Based Treatment for Anxiety, Depression, and ADHD for a Parent and Child.

Children with mental illness commonly live with caregivers who suffer from mental illness. Integrated mental-health-treatment approaches can provide more convenient and comprehensive care for families. This case report describes family-based treatment (FBT) for one parent/child dyad. The parent was a 37-year-old female with a history of anxiety and major depressive disorder and concern for symptoms of attention-deficit/hyperactivity disorder (ADHD). The child was an 8-year-old female with generalized anxiety disorder and concern for ADHD and behavioral problems. The parent received individual cognitive behavioral therapy (CBT) and parent management training. The child received CBT. Both also received medication management. The FBT team met regularly for coordinated treatment planning. Self-reported assessments via the Child Behavior Checklist showed meaningful improvement; anxiety decreased to nonclinical range week 12 and depression decreased to nonclinical range week 8. Clinician assessments showed improvement for both patients. Though more time intensive, FBT can yield significant improvement, particularly for children. Pragmatic approaches to treatment planning are important to minimize barriers to FBT.

Complex ADHD Challenging Case: When Simple Becomes Complex: Managing Clinician Bias and Navigating Challenging Family Dynamics in a 6-Year-Old Girl with ADHD and Developmental Delays.

CASE: Layla is a 6.7-year-old girl diagnosed with attention-deficit/hyperactivity disorder (ADHD)-predominantly hyperactive/impulsive type-delayed adaptive skills, enuresis, unspecified malnutrition, and feeding difficulties. She presented to developmental-behavioral pediatrics (DBP) in January 2022 due to caregiver concerns for autism spectrum disorder (ASD).Layla lives in a polyamorous family with her biological mother and father, mother's partner whom Layla refers to as her uncle, and her 2 half-siblings. There is a maternal history of special education services, schizoaffective disorder, bipolar disorder, multiple sclerosis, Wolff-Parkinson-White syndrome, and ADHD. Layla's father is a veteran diagnosed with post-traumatic stress disorder. Layla's siblings, aged 5 and 9 years, have established diagnoses of ADHD, ASD, global developmental delays, behavioral concerns, and poor sleep. There is a history of adverse childhood experiences, including parental mental health, poverty, and involvement with child protective services. Acknowledgement and inclusion of all members of this diverse family structure, as well as consistent validation from the DBP and social worker, allowed a strong treatment alliance to form and the mother continued to contact the DBP clinic, even for those questions related to other specialties. A social worker received weekly calls from the mother sharing grievances related to feeling misunderstood and spoke about the assumptions she felt external providers made about her family, culture, and parenting styles. For example, she recalls the pediatrician commenting about their family structure being "confusing for the children" and describing their home as "chaotic," assumptions that may not have been made of nuclear family structures. Behavioral therapies were a repeated recommendation, but the mother verbalized not being interested in these options as she had participated in parent management training several years earlier and felt that the strategies taught were not applicable to her unique family structure, to which the clinician replied, "this is the standard recommendation for all children this age with disruptive behaviors." Although the mother was initially hesitant to trial medications, she eventually agreed that Layla's symptoms were negatively affecting her school performance, and the DBP initiated a stimulant medication.Layla's initial evaluation included a developmental history, behavioral observations, and standardized testing. The results from developmental testing demonstrated age equivalents between 4 and 6 years across gross motor, adaptive, visual motor, and speech-language domains.On observation, Layla was extremely active. During the visit, she walked over to her mother, made eye contact, and showed her the picture that she had drawn. She engaged in imaginary play, reciprocal conversation, and responded to social bids. The mother felt strongly that Layla had ASD and reported symptoms such as motor stereotypies (hand flapping), covering ears with certain noises/sounds, and rigidity when it came to things being a certain way or a certain color. These behaviors did not occur in the initial or subsequent clinic visits with DBP, her general pediatrician, or during other outside evaluations the mother pursued. The DBP felt strongly that Layla was mimicking her siblings' symptoms and provided ongoing education regarding ADHD symptomology.In terms of behavior management, the mother did not attempt to redirect Layla's behaviors during the initial clinic visit and in subsequent visits, and both adult men yelled loudly, clapped, and hit their hands on the table as a form of redirection. The mother continued to voice her diagnostic disagreement with the DBP and the pediatrician and insisted that Layla met the criteria for ASD. When the mother reviewed the report, a statement insinuating that Layla's behaviors were "understandable given parental inconsistency and complicated family structure" upset her.What factors would you consider when thinking about caregiver disagreement with the diagnosis and treatment plan? Does diagnostic overshadowing apply here?

Integrating Structural and Experiential Family Therapy in Neurodivergent Families: A Case Study.

Autism Spectrum Disorder (ASD) is widely regarded as the most severe childhood behavioral disorder. However, society's lack of awareness regarding neurodevelopmental disorders, like autism, has led to a limited understanding of their profound impact on children and their families. Challenges include unique sensory experiences, communication and social interactions, strain on familial relationships, emotional toll on parents, and educational hurdles, which can significantly impact the well-being of individuals and their families. This case study explores the integration of Structural and Experiential Family Therapy in a neurodivergent family coping with ASD and Attention-Deficit/Hyperactivity Disorder (ADHD). Structural interventions focus on clarifying roles and redistributing caregiving responsibilities, addressing issues of communication, and power dynamics. Experiential interventions target emotion-focused techniques, empathy building, and cultural sensitivity training. This integration may promote lasting change in family dynamics and a call to empower parents within neurodivergent families through tailored interventions, contributing to a sustainable therapeutic approach.

[Development of an indicator set for the evaluation of the quality of routine ambulatory health care for common disorders in children and adolescents]. / Entwicklung eines Indikatorensets zur Evaluation der Versorgungsqualität in der ambulanten Routineversorgung häufiger Erkrankungen des Kindes- und Jugendalters.

BACKGROUND: In Germany, no consented quality indicator set (QI set) exists to date that can be used to assess the quality of pediatric care. Therefore, the aim of the project "Assessment of the quality of routine ambulatory health care for common disorders in children and adolescents" (QualiPäd) funded by the Innovation Committee of the Federal Joint Committee (grant no.: 01VSF19035) was to develop a QI set for the diseases asthma, atopic eczema, otitis media, tonsillitis, attention-deficit hyperactivity disorder (ADHD), depression and conduct disorder. METHODS: For the observation period 2018/2019, quality indicators (QIs) were searched in indicator databases, guidelines and literature databases and complemented in part by newly formulated QIs (e.g., derived from guideline recommendations). The QIs were then assigned to content categories and dimensions according to Donabedian and OECD and reduced by removing duplicates. Finally, a panel of experts consulted the QIs using the modified RAND-UCLA Appropriateness Method (RAM). RESULTS: The search resulted in a preliminary QI set of 2324 QIs. After the reduction steps and the evaluation of the experts, 282 QIs were included in the QI set (asthma: 72 QIs, atopic eczema: 25 QIs, otitis media: 31 QIs, tonsillitis: 12 QIs, ADHD: 53 QIs, depression: 43 QIs, conduct disorder: 46 QIs). The QIs are distributed among the following different categories: Therapy (138 QIs), Diagnostics (95 QIs), Patient-reported outcome measures/Patient-reported experience measures (PROM/PREM) (45 QIs), Practice management (31 QIs), and Health reporting (4 QIs). In the Donabedian model, 89% of the QIs capture process quality, 9% outcome quality, and 2% structural quality; according to the OECD classification, 61% measure effectiveness, 23% patient-centeredness, and 16% safety of care. CONCLUSION: The consented QI set is currently being tested and can subsequently be used (possibly modified) to measure the quality of routine outpatient care for children and adolescents in Germany, in order to indicate the status quo and potential areas for improvement in outpatient care.

A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD.

BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) may benefit from probiotics and prebiotics, but the effects are unclear. To determine whether probiotics and prebiotics affect children with ADHD, a systematic review was conducted. METHODS: The present systematic review analyzed cohort studies and randomized controlled trials that examined whether prebiotics and probiotics are associated with ADHD. Seven randomized controlled trials and two cohort studies met our inclusion criteria. RESULTS: Research on Lactobacillus rhamnosus GG (LGG) probiotic supplementation showed that children with ADHD had better emotional, physical, social, and school functioning, and a higher health-related quality of life compared to the placebo group. The studies also showed that Synbiotic 2000 reduces markers of intestinal and vascular inflammation in children with ADHD, in part through increasing SCFA levels. CONCLUSION: The use of probiotics and prebiotics as adjuvants therapy in patients with ADHD is beneficial. Further studies with longer duration, including more participants and a variety of age groups, and using various evaluation techniques such as in vivo observation are required to examine the effects of prebiotics and probiotics on ADHD.

Secondary analyses of sex differences in attention improvements across three clinical trials of a digital therapeutic in children, adolescents, and adults with ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) remains underdiagnosed and undertreated in girls. Inattentive symptoms, often predominant in girls with ADHD, represent a key driver of impairment and often persist into adulthood. AKL-T01 is a regulated digital therapeutic targeting inattention. We examined potential sex differences in the efficacy of AKL-T01 in three separate trials for 1) children, 2) adolescents, and 3) adults. METHODS: We conducted secondary analyses of clinical outcomes by sex in three AKL-T01 randomized clinical trials in ADHD (n1 = 180 children 30.6% female, M(SD) age = 9.71 (1.32); n2 = 146 adolescents; 41.1% female, M(SD) age = 14.34 (1.26); n3 = 153 adults; 69.9% female, M(SD) age = 39.86 (12.84)). Active treatment participants used AKL-T01 for 25 min/day over 4-6 weeks. Primary outcomes included change in attention on the Test of Variables of Attention (TOVA) and symptom change on the clinician-rated ADHD Rating Scale (ADHD-RS). To evaluate study hypotheses, we conducted a series of robust linear regressions of TOVA and ADHD-RS change scores by sex, adjusting for baseline scores. RESULTS: In children, girls demonstrated greater improvement in objective attention relative to boys following AKL-T01 (TOVA Attentional Composite Score; Cohen's d = .36 and Reaction Time Mean Half; Cohen's d = .54), but no significant sex differences in ADHD rating scale change. We did not observe significant sex differences in outcomes in the adolescent or adult trials. Limitations include binary sex categorization and slight study design variation across the three samples. CONCLUSION: AKL-T01 might notably improve attentional functioning in girls with ADHD relative to boys. Objective attention measures may be particularly important in the assessment of attentional improvement in childhood, given known gender biases in ADHD symptom reporting. We emphasize the importance of considering sex and gender-specific factors in ADHD treatment evaluation. TRIAL REGISTRATIONS: STARS ADHD CHILD: ClinicalTrials.gov ID NCT03649074; STARS ADHD ADOLESCENT: ClinicalTrials.gov ID NCT04897074; STARS ADHD ADULT: ClinicalTrials.gov ID NCT05183919.

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS).

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action. METHODS: A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment. DISCUSSION: This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD. TRIAL REGISTRATION: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD).

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.