Stimulant Research Articles

The Impact of Stimulant Medication on the Relation Between Working Memory and Activity Level in ADHD.

There is a positive association between heightened activity levels and improved working memory performance (WM) in individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). Recent research suggests that stimulant medications may have a simultaneous positive impact on WM and motor skills. Yet, it is unclear the specific connection between movement, WM, and stimulant use. We examined how visuospatial (VS) and phonological (PH) WM performance varied with children's stimulant medication usage and naturally occurring activity level. In a repeated measures design, children with ADHD (n = 43; 7-12years old) completed WM tasks while wearing actigraphy watches to monitor activity level on and off stimulant medication. Significant large sized main effects were observed for medication condition on PH (p < .05, ηp2 = .14) and VS (p < .001, ηp2 = .30) WM. Activity level also had significant medium sized main effects on PH (p < .01, ηp2 = .09) and VS (p < .005, ηp2 = .10) WM. There was a significant medium sized interaction for VS WM (p < .005, ηp2 = .11), indicating that the effect of medication on performance was greatest in the highest activity level category. The findings suggest that a combination of stimulant medication and an "optimal" level of movement may be most effective for improving VS WM.

Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life

We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and non-stimulants. From the dataset of a published network meta-analysis (Cortese etal., 20181), updated on 27th February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multi-level meta-analytic models were conducted with R 4.3.1. We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedges g= 0.51, 95% CI= 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults. In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and non-stimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and non-pharmacological interventions is likely to further improve QoL in people with ADHD. Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/;qvgps.

Impact of Treatment with Central Nervous System Stimulant and Risk of Substance Use Disorder in Adults with Attention-Deficit/Hyperactivity Disorder

Impact of Treatment with Central Nervous System Stimulant and Risk of Substance Use Disorder in Adults with Attention-Deficit/Hyperactivity Disorder

Omega-3 fatty acids supplementation prevents learning and memory impairment induced by chronic ethanol consumption in adolescent male rats through restoration of inflammatory and oxidative responses.

Ethanol (Eth) intake is known to cause numerous detrimental effects on the structure and function of the brain, and it is commonly used as a psychostimulant drug by adolescents. Conversely, omega-3 (O3) can reduce the risk of cognitive decline and promote the maintenance of neurophysiological functions. In this study, we investigated the protective effects of O3 on behavioral alterations, oxidative stress, and interleukin-6 (IL-6) levels induced by chronic Eth intake during adolescence in rats. Adolescent male rats (21 days old) were divided as follows: (1) Vehicle, (2) Eth (Eth in drinking water [20%]), (3-5) Eth + O3 (50/100/150 mg/kg), and (6) O3 (150 mg/kg). After 5weeks, Morris water maze (MWM) and passive avoidance (PA) tests were performed, and the hippocampal and cortical levels of oxidative stress markers and inflammatory indices were measured. Adolescent Eth intake impairs learning and memory function in MWM and PA tests (groups × day, p< 0.05 and p< 0.001, respectively). It was shown that Eth induced oxidative stress and neuroinflammation. O3 improved learning and impairment induced by Eth by reducing the adverse effects of Eth on the oxidant/antioxidant balance in the hippocampi (for malondialdehyde [MDA]/thiol: p< 0.01, p< 0.001, respectively) and for superoxide dismutase (SOD)/catalase (CAT): p< 0.01 and p< 0.05, respectively). Furthermore, we found that O3 prevented the Eth-induced increase of hippocampal IL-6 (p< 0.001). O3 supplementation acts as an effective approach to prevent learning and memory impairments induced by chronic Eth consumption during adolescence. In this respect, the antioxidant and anti-inflammatory properties of O3 seem to be the main underlying mechanisms of neuroprotection.

Value of estrogen pretreatment in patients with diminished ovarian reserve and elevated FSH on a line antagonist regimen: a retrospective controlled study.

The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied. We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared. The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D3 quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05). The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.

Ultrasound-Responsive Aligned Piezoelectric Nanofibers Derived Hydrogel Conduits for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) are considered as promising treatment strategy and frontier trend for peripheral nerve regeneration, while their therapeutic outcomes are limited by the lack of controllable drug delivery and available physicochemical cues. Herein, novel aligned piezoelectric nanofibers derived hydrogel NGCs with ultrasound (US)-triggered electrical stimulation (ES) and controllable drug release for repairing peripheral nerve injury are proposed. The inner layer of the NGCs is the barium titanate piezoelectric nanoparticles (BTNPs)-doped polyvinylidene fluoride-trifluoroethylene [BTNPs/P(VDF-TrFE)] electrospinning nanofibers with improved piezoelectricity and aligned orientation. The outer side of the NGCs is the thermoresponsive poly(N-isopropylacrylamide) hybrid hydrogel with bioactive drug encapsulation. Such NGCs can not only induce neuronal-oriented extension and promote neurite outgrowth with US-triggered wireless ES, but also realize the controllable nerve growth factor release with the hydrogel shrinkage under US-triggered heating. Thus, the NGC can positively accelerate the functional recovery and nerve axonal regeneration of rat models with long sciatic nerve defects. It is believed that the proposed US-responsive aligned piezoelectric nanofibers derived hydrogel NGCs will find important applications in clinic neural tissue engineering.

Psychotropic Medication Usage in Pediatric CKD: Reporting from the Chronic Kidney Disease in Children Cohort.

Mental health disorders (MHD) within the pediatric chronic kidney disease (CKD) population are prevalent. The frequency is unknown with which psychotropic medications that commonly treat these conditions are used in this population. Data from the Chronic Kidney Disease in Children (CKiD) cohort study were utilized to describe the use of psychotropic medications and patient-related characteristics of use. Medications were classified into 3 groups: antidepressants, CNS stimulants, and antipsychotic/mood stabilizing medications. Participant age, sex, CKD severity, and duration of medication use were ascertained. Medication use was evaluated in parallel with CKD disease type, presence of urological comorbidity, and hypertension. Chi-square tests compared subgroup medication use. Among 1074 CKiD participants (median baseline age 9.8 years), 6% (n=60) of participants used psychotropic medications at study entry with 11% reporting incident use of any medication category (n=120). CNS stimulants were most common at baseline. Antidepressants were more frequent among incident users at 7%. Use of two or more medications was rare (3%). Median eGFR at medication initiation was 45 ml/min|1.73m2. CNS stimulants were reported at a higher rate in males compared to females (p<0.05). 11% of CKiD patients report incident use of any psychotropic medication, with 7% reporting incident use of antidepressants. Future work is warranted to better ascertain the frequency, safety, and efficacy of psychotropic medication usage in relationship to formal MHD diagnoses in the pediatric CKD population.

Advancements in liquid chromatography‐mass spectrometry for amphetamine analysis in unconventional biological matrices: Focus on oral fluid and hair samples

AbstractAmphetamines (AMPHs) and their derivatives are potent central nervous system stimulants, in 2020 an astonishing 34 million regular users were reported worldwide. Consequently, there has been a critical need for the development of methods capable of detecting these compounds in alternative biological matrices. The review article discusses the analysis of amphetamines and their derivatives in alternative biological matrices, such as hair and oral fluid (OF), using liquid chromatography‐mass spectrometry. Compiles data from 28 articles published between 2012 and 2022, focusing on 13 articles on OFs and 15 on hair analysis. The article highlights the advantages of using these alternative matrices, including less invasive collection methods, greater sample stability, and simplified extraction processes. Additionally, prevalent analytical practices such as the use of C18 columns and the incorporation of formic acid and methanol into mobile phases are discussed. Furthermore, it demonstrates that the most used method for collecting OF is the Quantisal device, as well as solid phase extraction is also the most used for the same matrix. The review serves as a guide for researchers interested in analytical methods for identifying AMPHs, offering insights into advances, challenges, and the most used in the area.

Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study.

Stimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood. Investigate the long-term age-dependent effects of stimulant medication use on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD. This prospective study included the baseline and 4-year follow-up assessment of the "effects of Psychotropic drugs On the Developing brain-MPH" ("ePOD-MPH") project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness. A total of 32 male adolescents (aged mean ± SD, 11.2 ± 0.9 years at baseline) and 24 men (aged mean ± SD, 29.9 ± 5.0 years at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and more improvement of ADHD symptoms was associated with higher medication use in adults (P=0.001). We found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development.

Attention-deficit/hyperactivity disorder: clinical phenotypes, polymorphism of life-course manifestations, and therapeutic strategies

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that manifests in childhood and persists into adulthood. The prevalence of ADHD (USA/worldwide) in children and adolescents is 9.5/5.29 %, in adults — 4.4/2.5 %. The disorder has strong genetic correlations with numerous mental disorders and neurological diseases, in particular with post-traumatic stress disorder, addiction to cannabis, cocaine, recurrent and bipolar affective disorders, behavioral disorders, which is the biological basis of its clinical polymorbidity. Symptoms of ADHD overlap with other clinical manifestations of neurodevelopmental disorders (symptoms of autistic spectrum disorders, speech disorders, movement disorders, dyslexia, cognitive impairment), forming a polymorphic spectrum of pervasive developmental variants. Psychostimulants have been the standard of ADHD treatment for over 50 years. In 2002, atomoxetine became the first nonstimulant medication approved by the Food and Drug Administration for the treatment of ADHD, first in children and later in adult patients. Stimulant and nonstimulant medications have been shown to be effective in different phenotypes of ADHD (comorbidity with other mental and neurological disorders). In case of comorbidity of ADHD with anxiety, tics, atomoxetine has an advantage over stimulants and, together with alpha-2-adrenergic receptor agonists, can be recommended as the first drug. The presence of comorbid anxiety disorder or recurrent depression does not impact the efficacy and side effects of atomoxetine. Thus, atomoxetine is an effective drug and not only improves the symptoms of ADHD, but also plays a certain role in the treatment of patients with comorbid depression and anxiety.

Main Partner Relationships and the HIV Care Cascade: Examining the Predictive Utility of Sexual Agreements, Partner Concordance, and Drug Use Among Sexual Minority Men Living With HIV in the USA.

The past 15 years have seen increasing attention to relationship factors among sexual minority male (SMM) couples at high risk for HIV infection. Research has largely focused on HIV prevention outcomes. Outcomes relevant to SMM living with HIV have received relatively less attention. This study evaluated associations between relational covariates (relationship status, sexual agreements, and seroconcordance) and HIV care cascade outcomes (having a current antiretroviral therapy [ART] prescription, ART adherence, viral load (VL) testing, and VL detectability) above and beyond cannabis and stimulant drug use. Adult SMM (n = 36,874) living with HIV in the USA were recruited between November 1, 2017 and March 15, 2020 through social networking applications. They completed a cross-sectional survey online. Nonmonogamous SMM with serodiscordant partners were most likely to have an ART prescription. Those with seroconcordant partners (regardless of sexual agreements) were least likely to be adherent. While relational covariates were not associated with VL testing, SMM in nonmonogamous relationships with serodiscordant partners were significantly more likely to have an undetectable VL. Those in monogamous relationships with seroconcordant partners were significantly less likely to have an undetectable VL. SMM with seroconcordant partners and monogamous sexual agreements may experience diminished interpersonal motivation for HIV care engagement. HIV care cascade retention messages that emphasize the prevention of onward transmission may have limited relevance for these SMM. Novel intervention strategies are needed to enhance HIV care outcomes in this population, ideally ones that incorporate attention to drug use.

ADHD medication adherence reduces risk of committing minor offenses in adolescents.

This study aimed to investigate the association between adolescents' adherence to attention-deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12-18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64-0.71) or ≥6 months (HR 0.62, CI 0.59-0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non-stimulant medication, different offense categories and further sensitivity analyses. Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents.

Can Adverse Event Patterns Inform Shared Decision-Making in ADHD Treatment? A Systematic Review of Evidence From Registration Trials for FDA-Approved Treatments in Adults.

Adult patients and clinicians are faced with several pharmacological options to manage attention-deficit/hyperactivity disorder (ADHD). If types or rates of adverse experiences vary among these options, these differences could inform the shared decision-making process. To discern differentiating evidence-based patterns of risk, we analyzed data from FDA package labels for drugs approved to treat adult ADHD and reports from the registration trials used to create these labels. Three analyses of adverse effects were conducted: placebo-corrected occurrence at rates of 1 in 5, 10, and 20 participants, association with discontinuation, and uniqueness of occurrence within the treatment options. Among the 7 agents approved to treat adult ADHD, the number of types of side effects experienced during a mix of fixed and flexible-dose studies was greatest among the nonstimulant medications, but the stimulant medications had higher rates of occurrence of side effects. The minimum frequency at which all medications had adverse events was 1 in 10 participants. Overall discontinuation rates did not differ among the stimulant medications nor between stimulants and nonstimulants. To our knowledge, this is the first study to compile and compare data from all FDA registration trials for medications approved to treat adult ADHD. This article describes a process by which readily available adverse event reporting data can be used as a tool to inform shared clinical decision-making. While differences in the methodology and outcome reporting of the trials included may limit generalizability, the number of individual patients included and the completeness of the discontinuation data can be used to inform discussions with patients about the relative likelihood of adverse experiences and other patient concerns.

Network pharmacology of xylazine to understand its health consequences and develop mechanistic-based remediations

The recent rise in xylazine use disorders (XUD) in humans is a significant cause for concern as a comprehensive understanding of its molecular pathology is limited, and hence, the ability to reverse the potential adverse effects is lacking. To address this gap, this study evaluates the dose-dependent impact of xylazine and its interactions with various potential targets to identify an optimal reversal strategy. A trichotomized (Low, medium, and high) dose, volume of distribution, and predicted plasma concentration of xylazine were defined. A detailed analysis of xylazine's network protein targets and their tissue-specific expression was performed using classical pharmacoinformatic tools. Molecular docking was used to assess the drug-target affinities and identify potential reversal agents. The study categorized xylazine plasma concentrations ranging from 5-8 µM, 14-20 µM, and 28-40 µM as low, medium, and high concentrations, respectively. Xylazine displayed a preferential affinity for hydrolases, kinases, transporters, and ion channels. Xylazine's network analysis revealed the following proteins: ABCC9, RET, RAPGEF4, ACHE, TGFBR1, PGR, KCNH2, KCNN2, and TRPM8 as its high-affinity targets. The tissue-specific expression of these high-affinity targets suggested potential adverse effects on various organs, particularly skeletal and smooth muscles and the adrenal gland. The study further explored the potential reversal of xylazine pharmacology using alpha2ARantagonists and CNS stimulants. Prazosin emerged as the most promising candidate, exhibiting a 200 to 2000-fold superior affinity against all high-affinity targets of xylazine. This study contributes to our understanding of xylazine's molecular mechanisms, which could be relevant to its pharmacological effects in all species, and suggests that prazosin can serve as an effective therapeutic option for mitigating xylazine-induced adverse effects in XUD patients, which warrants clinical investigation.

EXERCISE IN ADULTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER: A SYSTEMATIC REVIEW

INTRODUCTION &amp; AIMS Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in adults. Stimulant medications are first-line treatments, they have many side effects and do not address common comorbidities such as cardiometabolic disease, depression, and anxiety. Exercise, by contrast, not only improves ADHD symptoms in youth but effectively treats such comorbidities, making it a potentially valuable treatment option. However, exercise efficacy in adults with ADHD has not been systematically reviewed. Therefore, we aimed to summarise the results of acute exercise and training interventions on health-related outcomes for adults with ADHD, including ADHD symptoms, cognitive function, and psychological well-being. METHODS Using PRISMA guidelines, fifteen databases were searched (including grey literature) on 27/08/2020, yielding 22,088 unique publications. Database alerts were created to capture additional studies (n= 2). Screening, data extraction, Risk of Bias and GRADE assessment was conducted by CEHB. RESULTS Seven acute (6 cycling, 1 self-selected, 1 yoga) and 6 training studies (Yoga, Pilates, Kickboxing, Tai Chi, General Coordination, Group Circuit Class, Cycling) were included. Among acute studies, those reporting small-to-moderate improvements in cognitive function were characterised by longer duration exercise (&amp;gt;30 minutes), withholding ADHD medication before exercise, and using cohorts with clinician-confirmed ADHD diagnosis. Among the training studies, only one reported an improvement in cognition following Pilates when compared to an inactive control. It was longer (6 months vs. &amp;lt;8 weeks), prescribed progressive intensity and volume, and had high adherence compared to the non-significant trials. The certainty of evidence was low or very low for all outcomes. CONCLUSIONS Overall, acute exercise may have a small positive effect on cognition in adults with ADHD; however, certainty of the evidence is low. Further research is needed to investigate the impact of different modalities, durations, and intensities of acute exercise and chronic exercise on adult ADHD.

Filgrastim Use in the Treatment of Azathioprine-Induced Myelosuppression Toxicity After Prescription Error in the Feline.

Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.

Major biochemical constituents of Premna integrifolia extract: A Review of chemical analysis

Premna integrifolia (Ganimari) is a precise widespread medicinal herb developed mainly in Sri Lanka and different regions of India. The plant grows wild in coastal districts of Andhra Pradesh, Orissa, West Bengal, Tamil Nadu and Kerala in India. Premna integrifolia, a valuable herb in Ayurveda, has many health advantages including analgesic, anti-inflammatory, antibacterial, antiarthritic, antioxidant, anti-ulcer, antidiabetic, CNS stimulant, hepatoprotective, cardiac stimulant, hypolipidemic and neurodegenerative disease-fighting properties. This review discusses the challenges and analytical approaches for determining the chemical components of Premna integrifolia, both quantitatively and qualitatively. This review also provides a thorough analysis of the methods used to accurately characterize the chemical profile of Premna integrifolia extract. The effectiveness of analytical methods like chromatography, UV-spectroscopy and mass spectrometry in identifying and quantifying bioactive constituents is being investigated.

Evaluating Effectiveness of Group Intervention Working on Executive Function for Children with Attention Deficit Hyperactivity Disorder: A Prospective Observational Cohort Study

Introduction: The objective of this study is to evaluate the effectiveness of Simon says program (SSP), a strategy-based group intervention program working on executive function (EF) for children with attention deficit hyperactivity disorder (ADHD). Methods: A prospective observational cohort study was conducted from December 2021 to July 2022 recruiting 21 SSP participants, either they were on stimulant or not on stimulants, and 12 other ADHD patients who are on stimulant medication only without prior participation in SSP, using convenience sampling method, from Child Development Clinic Hospital Sultan Ismail. NICHQ Vanderbilt Assessment Follow Up Scales (VAS) were used to measure its effectiveness and the significance of score differences before and after SSP were assessed using paired sample t-test of Statistical Package for Social Science (SPSS) version 28.0 software. Results: Total of 33 children participated in the study. From our study, only those participants on behavioural therapy alone showed statistically significant reduction in inattentive score, hyperactivity score and total symptoms score at the third month and sixth month after joining SSP from parents-rated VAS. There were no statistically significant differences in the average VAS performance score for both groups. Conclusion: SSP could be an effective behavioral intervention for children with ADHD children. Limitations included lacking clear generalizability due to the convenience sampling method and potential inter-rater variability.

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)

BackgroundAttention 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.MethodsA 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.DiscussionThis 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.

A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are neurodevelopmental conditions which frequently co-occur. The Autism Diagnostic Observation Schedule (ADOS) is commonly used to aid with diagnostic assessment of ASD but was not originally designed for use in those with comorbid ADHD. Visual attention to social stimuli has been often studied in ASD using eye-tracking, to obtain quantitative indices of how attention is deployed to different parts of a social image/scene. As the ADOS includes tasks that rely on attending to and processing images of social scenes, these measures of visual attention could provide useful additional objective measurement alongside ADOS scores to enhance the characterisation of autistic symptoms in those with ADHD. Children with ASD, comorbid ASD and ADHD, ADHD and Neurotypical (NT) controls were recruited (n=84). Visual attention was measured using eye-tracking during free viewing of social scenes selected from the ADOS. The full ADOS was then administered. Stimulant medication was temporarily withdrawn during this assessment. Research diagnoses were based on the Development and Wellbeing Assessment (DAWBA), ADOS, Social Communication Questionnaire (SCQ, a measure of ASD severity) and Conners' Rating Scales (CRS-3, a measure of ADHD severity) following clinical consensus. Using factorial ANOVAs to model ADHD, Autism and their interaction, we found that fixation duration to faces was reduced in those with ASD (ASD and ASD+ADHD) compared to those without ASD (ADHD and NT). Reduced visual attention to faces in the whole sample was associated with Autism symptom severity (SCQ subscale scores) but not ADHD symptom severity (CRS-3 scores). Our findings provide preliminary evidence in support of implementing visual attention measurement during assessment of ASD in the context of comorbidity with ADHD. For example, if a child with ADHD was found to reduce attention to faces in ADOS pictures this may suggest additive difficulties on the autism spectrum. Replication across a larger sample would be informative. This work has future potential in the clinic to help with complex cases, including those with co-occurring ADHD and ASD.