Assessment of centanafadine in adults with ADHD: a matching adjusted indirect comparison versus methylphenidate hydrochloride extended release (Concerta).

OBJECTIVE: To compare safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD. METHODS: Without head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) of adverse event rates reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER were conducted. Pooled patient-level data from two centanafadine trials (NCT03605680/NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e. >99th percentile). RESULTS: Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: -11.95), initial insomnia (-11.10), decreased appetite (-8.05), anxiety (-5.39), palpitations (-5.25), and feeling jittery (-4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER. CONCLUSION: In this MAIC, centanafadine had better safety and possibly lower efficacy than methylphenidate hydrochloride ER. While safety results were robust across analyses, there was no efficacy difference between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern.

Event segmentation in ADHD: neglect of social information and deviant theta activity point to a mechanism underlying ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed psychiatric conditions in children and adolescents. Although the symptoms appear to be well described, no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD face. Aims: The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in ADHD. Methods: Adolescents with ADHD and neurotypically developing (NT) peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the movie. Concomitantly recorded electroencephalography (EEG) data were analysed for differences in frequency band activity and effective connectivity between brain areas. Results: Compared with their NT peers, the ADHD group showed less dependence of their segmentation behaviour on social information, indicating that they did not consider social information to the same extent as their unaffected peers. This divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source level. Specifically, NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing, which was not the case in the ADHD group. For the ADHD group, the inferior frontal cortex associated with attentional sampling served as a hub instead, indicating problems in the deployment of attentional control. Conclusions: This study shows that adolescents with ADHD perceive events differently from their NT peers, in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental information. The results call for a novel conceptual view of ADHD, based on event segmentation theory.

Effects of Practicing Closed- vs. Open-Skill Exercises on Executive Functions in Individuals with Attention Deficit Hyperactivity Disorder (ADHD)-A Meta-Analysis and Systematic Review.

(1) Background: Previous studies have identified discrepancies in improvements in executive functioning in typically developing children when comparing closed- and open-skill exercise interventions. However, there is limited research on executive functioning in attention deficit hyperactivity disorder (ADHD). This study aims to conduct a systematic review and meta-analysis to explore the impact of closed- and open-skill exercises on ADHD populations. (2) Methods: The PRISMA guidelines for systematic reviews were followed to search seven databases to evaluate and analyze studies published from 2013 to 2023. Prospero: CRD42023460452. (3) Results: A meta-analysis of 578 subjects with ADHD in 11 RCTs (Randomized control trial) and 3 NRS (Non-randomized studies) revealed that closed-skill exercise significantly improved executive function subdomains, including inhibitory control (standardized mean differences (SMD) = -1.00), cognitive flexibility (SMD = -1.33), and working memory (SMD = -0.85). Furthermore, open-skill exercise was found to have a positive effect on inhibitory control (SMD = -1.98) and cognitive flexibility (SMD = -0.97) in ADHD patients. Both types of exercise interventions demonstrated an improvement in executive function compared to controls, with open-skill exercises exhibiting superior effects (Qb = 6.26). (4) Conclusions: The review recommends a 12-week intervention cycle with exercise at least twice a week of moderate or higher intensity as suitable for ADHD individuals. This review also encourages individuals with ADHD to engage in exercises involving multiple motor skill types.

Comparison of arterial spin labeled MRI (ASL MRI) between ADHD and control group (ages of 6-12).

This study utilized arterial spin labeling-magnetic resonance imaging (ASL-MRI) to explore the developmental trajectory of brain activity associated with attention deficit hyperactivity disorder (ADHD). Pulsed arterial spin labeling (ASL) data were acquired from 157 children with ADHD and 109 children in a control group, all aged 6-12 years old. Participants were categorized into the age groups of 6-7, 8-9, and 10-12, after which comparisons were performed between each age group for ASL analysis of cerebral blood flow (CBF). In total, the ADHD group exhibited significantly lower CBF in the left superior temporal gyrus and right middle frontal gyrus regions than the control group. Further analysis revealed: (1) The comparison between the ADHD group (N = 70) aged 6-7 and the age-matched control group (N = 33) showed no statistically significant difference between. (2) However, compared with the control group aged 8-9 (N = 39), the ADHD group of the same age (N = 53) showed significantly lower CBF in the left postcentral gyrus and left middle frontal gyrus regions. (3) Further, the ADHD group aged 10-12 (N = 34) demonstrated significantly lower CBF in the left superior occipital region than the age-matched control group (N = 37). These age-specific differences suggest variations in ADHD-related domains during brain development post age 6-7.

Family resilience and caregiver's well-being across different age groups of children with ADHD in the United States: a cross-sectional study.

PURPOSE: This study aimed to investigate the impact of family resilience on caregiver well-being across various age groups of children diagnosed with ADHD (attention-deficit/hyperactivity disorder) groups (0-5, 6-11, and 12-17 years). METHODS: Utilizing secondary data from the 2022 US National Survey of Child Health, this cross-sectional study involved 2,752 children who were formally diagnosed with ADHD. Statistical analysis included descriptive analysis, Spearman's rank correlation, chi-square tests, and linear regression, conducted using SPSS version 27. RESULTS: The study revealed a moderate positive correlation (r=.35, p<.001) between family resilience and caregiver well-being. Controlling for covariates, family resilience accounted for 25.2%, 21.1%, and 22.1% of caregiver well-being variance in age groups 0-5, 6-11, and 12-17 years, respectively. Additionally, factors like employment status, family structure, and caregiver age showed varying influences on caregiver well-being across these developmental stages. A consistent pattern emerged across these age groups: unemployment and non-traditional family structures were associated with negative impacts on caregiver well-being, whereas older caregiver age positively influenced well-being. CONCLUSION: This research underscores the importance of age-specific family resilience strategies to improve caregiver well-being and family interactions in ADHD contexts. Investigating these aspects through qualitative studies across various cultures could deepen our understanding of well-being and inform culturally sensitive interventions.

Sex Differences in Diagnosis and Treatment Timing of Comorbid Depression/Anxiety and Disease Subtypes in Patients With ADHD: A Database Study.

OBJECTIVE: Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD. METHOD: To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences. RESULTS: Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients. CONCLUSIONS: Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment.

Changed sleep according to weighted blanket adherence in a 16-week sleep intervention among children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: To examine differences in sample characteristics and longitudinal sleep outcomes according to weighted blanket adherence. METHODS: Children with attention-deficit/hyperactivity disorder (ADHD) (n =94), mean age 9.0 (sd 2.2, range 6-14) participated in a 16-week sleep intervention with weighted blankets (WB). Children were classified as WB adherent (use of WB ≥ 4 nights/week) or non-adherent (use of WB ≤ 3 nights/week). Changes in objectively measured sleep by actigraphy, parent-reported sleep problems (Children's Sleep Habits Questionnaire (CSHQ)) and child-reported Insomnia Severity Index (ISI) were evaluated according to adherence with mixed effect models. Gender, age, and ADHD subtype were examined as potential moderators. RESULTS: Children adherent to WBs (48/94) showed an early response in sleep outcomes and an acceptance of the WB after four weeks of use as well as a decrease in parent- (CSHQ) (-5.73, P = .000) and child-reported sleep problems (ISI) (-4.29, P = .005) after 16 weeks. The improvement in sleep was larger among WB adherent vs. non-adherent (between-group difference: CSHQ: -2.09, P = .038; ISI: -2.58, P =.007). Total sleep time was stable for children adherent to WB but decreased for non-adherent (between-group difference: +16.90, P = .019). CONCLUSIONS: An early response in sleep and acceptance of the WB predicted later adherence to WBs. Improvements in sleep were more likely among WB adherents vs. non-adherents. Children with ADHD may thus benefit from using WBs to handle their sleep problems.

Increased Serum Terminal Complements Complex Levels in Attention Deficit Hyperactivity Disorder Children.

Background: Attention deficit hyperactivity disorder (ADHD) is a widespread neuropsychiatric disorder in both children and adolescents, which is associated with social isolation and poor academic performance. Complement proteins are regarded as a major player in inflammation and disease development for several neuropsychiatric diseases such as schizophrenia and bipolar diseases. As clarified by previous data, increased levels of complement molecules and other immunological markers as cytokines were demonstrated in these disorders. Limited studies have investigated complement proteins particularly terminal complement complex or membrane attack complex (C5b-9) among ADHD patients. The present research aims to elucidate the association between C5b-9 complex protein and ADHD. Methods: This is a cross-sectional study. Sera were collected from Al-Hussain Teaching Medical City in Holy Karbala, Iraq, during 2019-2020. Sera were tested for C5-b9 using commercial kits by enzyme-linked immunosorbent assay (ELISA). Results: In 90 participants included in the study, a significant increment in C5b-9 levels among ADHD patients (P=0.019) was observed. Patients with positive C5b-9 levels had a 2.76 times higher risk of developing ADHD than control subjects. The diagnostic utility for C5b-9 was statistically significant with 71.11% sensitivity, 55.6% specificity, and a high negative predictive value (97.3%). Conclusion: The study concluded elevation of the C5b-9 terminal complements complex levels in ADHD patients, which could point to the association of complement proteins as inflammatory markers with the ADHD disease process.

Diagnosis and Treatment of ADHD in the Pediatric Population.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.

Attention-Deficit/Hyperactivity Disorder as a Potential Risk Factor for Dementia and Other Neurocognitive Disorders: A Systematic Review.

Background: Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental condition now recognized to persist into older adulthood, has been postulated to be a risk factor for neurocognitive disorders given the overlap in clinical features and neurobiology, as well as the complex interplay between ADHD and known risk factors for dementia. Studies have emerged assessing this relationship, but there has not yet been a comprehensive systematic review addressing this topic. Objective: To assess whether ADHD is a risk factor for neurocognitive disorders and to explore possible mechanisms for such an association. Methods: A systematic review of the literature was conducted using Medline, Embase, and PsycINFO from inception until June 4, 2023. Studies were included if they assessed whether or how ADHD may be a risk factor for neurocognitive disorders. Studies were excluded if they were not primary literature, not published in a peer-reviewed journal, not in English, and/or used non-human subjects. Study quality was assessed using the QualSyst tool. Results: Sixteen studies met inclusion criteria. Seven studies found a positive association between ADHD and neurocognitive disorders (all-cause dementia in four studies, Alzheimer's disease in three studies, Lewy body dementia in two studies, and mild cognitive impairment in one study). Four studies did not find an association. Five studies pertained to possible mechanisms for an association, including genetics, with minimal significant findings. Conclusions: ADHD may be a risk factor for certain neurocognitive disorders, although the evidence base is limited, and the absolute risk is small. Possible explanations include genetic and lifestyle factors.

Attention-deficit hyperactivity disorder and psychostimulant use in patients seeking dental care-Associations with common orofacial pain complaints.

BACKGROUND: Dental medicine should expand its scope to properly assess medical and psychosocial factors that might have an impact on patients' oral health. Based on previous literature and clinical experience, attention-deficit/hyperactivity disorder and psychostimulant medications might represent factors associated with orofacial pain symptoms. OBJECTIVE: The aim of the study was to assess whether common orofacial pain complaints such as jaw pain, jaw clicking, teeth clenching and headaches are more prevalent in dental patients who have an ADHD diagnosis and/or use psychostimulant medications. METHODS: Orofacial pain symptoms prevalence was compared among four groups from a sample of new patients seeking dental care at Tufts University School of Dental Medicine (n = 11 699) based on ADHD diagnosis and psychostimulants intake: G1: no ADHD, no stimulants; G2: yes ADHD, yes stimulants; G3: yes ADHD, no stimulants; G4: no ADHD, yes stimulants. RESULTS: In multivariable logistic regression models adjusting for age, gender, tobacco use, and alcohol consumption, significant differences were found for clenching (p < .0001), jaw pain (p < .0001), and headache (p < .0001). Compared to G1, two groups (G2 and G4) exhibited significantly higher odds of clenching and headaches, whereas only G2 exhibited significantly higher odds of jaw pain. CONCLUSIONS: In comparison with patients without ADHD and not taking psychostimulants medications, dental patients using psychostimulants with and without ADHD diagnosis report headaches and teeth clenching more frequently, while jaw pain is reported more frequently only by those taking psychostimulants with an ADHD diagnosis. Further research is necessary to assess the nature of these associations and their clinical relevance.

The Relationship between Gene SLC6A3 Variable Number of Tandem Repeat (VNTR) and Attention-Deficit/Hyperactivity Disorder.

Objective : This research investigates the alleles of Variable Number of Tandem Repeats (VNTR) intron 8 of the gene SLC6A3 with attention-deficit / hyperactivity disorder (ADHD) in children and adolescents. Method : The study's target population consisted of children and adolescents referred to the specialized clinic, as well as students attending school in Rasht city during 2021-2022. A sample of 95 children between the ages of 6 and 10 with ADHD was selected as the ADHD group, and 95 healthy children were selected as the control group using purposive sampling. The subjects completed the Child Symptom Inventory-4 (CSI-4) checklist after a clinical interview, and demographic information was collected. Genetic sampling was carried out through hair follicles. The sequence of interest was proliferated using the Polymerase Chain Reaction technique )PCR(; afterward, the samples were used for genotype identification on polyacrylamide gel electrophoresis. Results: The chi-square test results indicated that the 5R / 5R genotype (P = 0.026, χ2 = 7.26) and the 5R allele (P = 0.002, χ2 = 9.35) had a higher frequency compared to the control group. Additionally, the odds ratio test indicated that, compared to other genotypes and alleles, the 5R / 5R genotype (OR = 2.75, 95% CI = 1.29-5.82, P = 0.01) and the 5R allele (OR = 2.02, 95% CI = 1.28-3.19, P = 0.002) increase the odds of developing ADHD by 2.7 and 2 times higher, respectively. Conclusion: The present study successfully showed the association between intron 8 gene polymorphism, which is responsible for encoding the dopamine transporter as well as ADHD in children and adolescents in Iran.

Long-term effects of adenotonsillectomy in children with attention deficit hyperactivity disorder.

STUDY OBJECTIVES: Adenotonsillectomy (AT) improves short-term symptoms of attention deficit hyperactivity disorder (ADHD) in children; however, its long-term effects remain unclear. We aimed to verify the therapeutic long-term effects of AT in children with ADHD. METHODS: This retrospective control study included children ages < 18 years who were diagnosed with ADHD and receiving ADHD medications. Participants were divided into groups depending on whether AT was performed (AT [+] or AT [-] groups) and matched 1:1 for age, sex, and year and month of diagnosis using randomized nonreplacement selection. RESULTS: Among patients with ADHD (n = 171,112), 3,615 underwent AT. In both groups, the number of drugs taken gradually increased before and decreased after the AT date (ATD). There was no difference in the number of drugs used before (P = .88) and after ATD (P = .06). Before ATD, the average number of outpatient visits (nOV) did not change in both groups (AT [+]: P = .12; AT [-]: P = .71). After ATD, the average number of outpatient visits decreased only in the AT (+) group (P = .001). However, there was no difference in the average number of outpatient visits between the two groups before (P = .47) and after ATD (P = .17). Before ATD, methylphenidate doses between the groups were not different (P = .06); however, a significant increase was noted after ATD in the AT (+) group (P < .001). CONCLUSIONS: AT does not result in significant long-term therapeutic effects in terms of medication use and health care utilization in children with ADHD. CITATION: Lee J, Choi A, Kim S, Kim K. Long-term effects of adenotonsillectomy in children with attention deficit hyperactivity disorder. J Clin Sleep Med. 2024;20(5):727-733.

The Meaning of Physical Education Practice in Students with Attention-Deficit Hyperactivity Disorder (ADHD).

Purpose: This study seeks to describe the perspective of students with attention-deficit hyperactivity disorder (ADHD) and physical education (PE) teachers concerning physical activity practice in high school. Methods: A qualitative descriptive study based on an interpretative framework was conducted with secondary school students with ADHD, and their teachers of physical education. In-depth interviews and researchers' field notes were used to collect the data. Purposive sampling and inductive thematic analysis were applied. Results: Results show that ADHD is not experienced as limiting the practice of PA and PE by students, except in motor activities that require concentration such as tactical games. On the contrary, PA and PE helps them feel better. Teachers have not had to make extensive methodological modifications in their teaching styles with students with ADHD in relation to other situations or incidents. Conclusions: Students with ADHD do not seem to show significant difficulties in PE lessons or in the practice of extracurricular PA. PE teachers do not need to make significant adaptations with these students.

Validation and bifactor structure of the French Adult ADHD Symptoms Rating Scale v1.1 (ASRS).

BACKGROUND: Three scoring methods for the widely available Adult ADHD Symptoms Rating Scale v1.1 (ASRS) have been proposed to screen for ADHD, but these three methods have rarely been compared against formal clinical diagnoses. We aimed to validate the French version of the ASRS against a clinical interview using DSM-IV and DSM-5 diagnostic algorithms. METHODS: One hundred five adults from a convenience sample were evaluated with the ASRS and the DIVA 2.0, using both DSM-IV and DSM-5 criteria. We used Confirmatory Factor Analysis to investigate the underlying structure of the ASRS. Sensitivity, specificity, and classification accuracy were compared between the rating algorithms of the ASRS. RESULTS: The full score method had worse predictive performance than the Screener and the 2-stage scoring method. All characteristics of the three scoring methods for the ASRS were worse when applying DSM-5 criteria. The best-fitting structure was a bi-factor model with a general ADHD factor and three specific factors. CONCLUSIONS: ADHD was best conceived as a one-dimensional construct. The 2-stage scoring method superseded the Screener with comparable sensitivity and specificity.

Clinical practice guidelines for attention-deficit/hyperactivity disorder: recent updates.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders found in children and adolescents. The American Academy of Pediatrics (AAP) first published a clinical practice guideline on ADHD in 2000, which was revised in 2011 and republished together with an accompanying process-of-care algorithm. More recently, the 2019 clinical practice guideline revision was published. Since the 2011 guideline, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), was released. In addition, the Society of Developmental and Behavioral Pediatrics (SDBP) recently released another clinical practice guideline for complex ADHD. Although there are nonessential changes reflected in these updates, a number of changes have still been made; for example, the DSM-5 criteria lowered the diagnostic threshold for ADHD in older teens and adults. Additionally, the criteria were revised to facilitate application to older teens and adults, and a comorbid diagnosis with autism spectrum disorder is now allowed. Meanwhile, the 2019 AAP guideline added the recommendation related to comorbid conditions with ADHD. Lastly, SDBP developed a complex ADHD guideline, covering areas such as comorbid conditions, moderate-to-severe impairment, treatment failure, and diagnostic uncertainty. In addition, other national ADHD guidelines have been published, as have European guidelines for managing ADHD during the coronavirus disease 2019 pandemic. To facilitate ADHD management in a primary care, it is important to provide and review clinical guidelines and recent updates. In this article, we will review and summarize the recent clinical guidelines and their updates.

Expected changes in parenting after an online parent training for ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. Treatments for this population should be multidisciplinary and must be initiated as early as possible. Non-pharmacological interventions for ADHD include psychoeducation, parent behavioural training programs and school interventions and accommodations. In response to the COVID-19 pandemic, we developed an online version of a combined psychoeducation and behavioural training program to facilitate access to mental health treatment and ensure continuity of care. OBJECTIVE: The study assessed the acceptability of this online parent training program, among parents and caretakers of children and adolescents with ADHD. METHODS: The program consisted of ten online sessions over the course of two consecutive days (five sessions a day). Satisfaction, usefulness and general comments about the program were assessed with open-ended questions and visual-analogous scales. Parents/caretakers' use of strategies to manage behavioural problems was assessed using the Parenting and Family Adjustment Scales. RESULTS: A total of 206 parents participated in the online program 175 of whom completed the evaluation. Participants were satisfied with the content of the program. More than half of participants had already started using strategies included in the program. The engagement was high and no major obstacles were identified other than some internet connection issues. DISCUSSION: In our survey, online delivery was described as more convenient, and participants were satisfied with the content of the program finding it beneficial for their child. Despite this, some difficulties in implementing new strategies were observed. Online BTP increased access to the BTP programs while being effective on ADHD symptoms and behavioural disturbances. CONCLUSIONS: With these measures, we hope to improve engagement in online psychoeducation and behavioural therapy programs. Future research evaluating online behavioural training programs should focus on ways to make them more accessible and adaptable to families' obstacles.