Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder

JPliszka Steven R., Wilens Timothy E., Bostrom Samantha, Arnold Valerie K., Marraffino Andrea, Cutler Andrew J., López Frank A., DeSousa Norberto J., Sallee Floyd R., Incledon Bev, Newcorn Jeffrey H., and On behalf of the HLD200-108 Study Group. Journal of Child and Adolescent Psychopharmacology. August 2017, 27(6): 474-482.

Objective: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) formulation consisting of uniform, dual-layered microbeads with an inner drug-loaded core. DR/ER-MPH is designed to delay the initial release of drug by 8–10 hours, and thereafter, provide a controlled, extended drug release to target onset of effect upon awakening that lasts into the evening. This phase 3 study evaluated the safety and efficacy of DR/ER-MPH on symptoms and temporal at-home functional impairment in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: This 3-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, forced-dose titration trial evaluated DR/ER-MPH (40–80 mg/day) in children aged 6–12 years with ADHD. Primary efficacy endpoint was the ADHD rating scale–IV (ADHD-RS-IV), and the key secondary endpoints were the Before-School Functioning Questionnaire (BSFQ), and Parent Rating of Evening and Morning Behavior-Revised, morning (PREMB-R AM) and evening (PREMB-R PM). Safety measures included spontaneously reported treatment-emergent adverse events (TEAEs) and two TEAEs of special interest, appetite suppression and insomnia (with direct questioning on sleep disturbance).

Results: One hundred sixty-one participants were included in the intent-to-treat population (DR/ER-MPH, n = 81; placebo, n = 80). After 3 weeks, DR/ER-MPH achieved significant improvements versus placebo in ADHD symptoms (least-squares [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; p = 0.002), and at-home early morning (LS mean BSFQ: 18.7 vs. 28.4; p < 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; p < 0.001) and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; p = 0.002) functional impairment. Commonly reported TEAEs (≥10%) were insomnia and decreased appetite.

Conclusions: DR/ER-MPH was generally well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and at-home functional impairments in the early morning, late afternoon, and evening in children with ADHD.

ADHD in children and young people: prevalence, care pathways, and service provision

Sayal, Kapil , Prasad Vibhore,  Daley David, Ford Tamsin, Coghill, David . ADHD in children and young people: prevalence, care pathways, and service provision Lancet Psychiatry 2017.  Published Online October 9, 2017 http://dx.doi.org/10.1016/

Attention-deficit hyperactivity disorder (ADHD) is a common childhood behavioural disorder. Systematic reviews indicate that the community prevalence globally is between 2% and 7%, with an average of around 5%. At least a further 5% of children have substantial difficulties with overactivity, inattention, and impulsivity that are just under the threshold to meet full diagnostic criteria for ADHD. Estimates of the administrative prevalence (clinically diagnosed or recorded) vary worldwide, and have been increasing over time. However, ADHD is still relatively under-recognised and underdiagnosed in most countries, particularly in girls and older children. ADHD often persists into adulthood and is a risk factor for other mental health disorders and negative outcomes, including educational underachievement, difficulties with employment and relationships, and criminality. The timely recognition and treatment of children with ADHD-type difficulties provides an opportunity to improve long-term outcomes.

This Review includes a systematic review of the community and administrative prevalence of ADHD in children and adolescents, an overview of barriers to accessing care, a description of associated costs, and a discussion of evidence-based pathways for the delivery of clinical care, including a focus on key issues for two specific age groups—younger children (aged ≤6 years) and adolescents requiring transition of care from child to adult services.

Antidepressant use in early pregnancy does not increase autism & ADHD risk in kids

Large-scale analysis suggests fewer risks than previously thought from exposure to antidepressant medications in early pregnancy | ScienceDaily


A study led by Indiana University suggests that mothers’ use of antidepressants during early pregnancy does not increase the risk of their children developing autism or attention deficit hyperactivity disorder, conditions previously associated with these medications.

The research, reported today in the Journal of the American Medical Association, found significant evidence for only a slight increase in risk for premature birth in the infants of mothers who used antidepressants during the first trimester of pregnancy.

After controlling for multiple other risk factors, the researchers did not find any increased risk of autism, ADHD or reduced fetal growth among exposed offspring. The risk for premature birth was about 1.3 times higher for exposed offspring compared to unexposed offspring.

Read the full commentary here

The original research abstract is available here

Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms

Boucher, O. et al. Pediatric Research. Published online: 4 January 2017


Background: Several studies have related longer breastfeeding duration to better intellectual performance in children. By contrast, few studies have investigated the potential protective effects of breastfeeding against behavioral problems such as attention deficit hyperactivity disorder (ADHD) symptoms, and even fewer on autism spectrum disorders (ASD) traits.

Conclusion: This study provides further evidence of a positive association of breastfeeding with cognitive function apart from socio-environmental factors, and also suggests a protective role against autistic traits. Results are in agreement with recommendations for prolonged breastfeeding duration to promote child development.

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Associations between allergic diseases and ADHD/ODD in children

Lin, Y-T. et al. (2016) Pediatric Research. 80. pp. 480–485

Background:We aim to investigate the detailed associations between allergic diseases with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among children.

Methods: Clinical information from 2,896 children enrolled in the Taiwan Children Health Study was obtained for analyses. Allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis, have been evaluated based on the questions adjusted from International Study of Asthma and Allergies in Childhood. The Swanson, Nolan, and Pelham questionnaire was used to assess symptoms of ADHD and ODD. Symptoms of depression, stress, and poor sleep quality were evaluated as the interactive risk factors.

Results: Children having symptoms of allergic diseases within the past 1 y were associated with having all dimensions of symptoms of ADHD and ODD. Children with ever having a physician-diagnosed atopic dermatitis were associated with inattentive and hyperactive–impulsive symptoms of ADHD. Ever diagnosed asthma was associated with ADHD and ODD. Ever diagnosed allergic rhinitis was associated with inattentive and combined symptoms of ADHD and ODD.

Conclusion: Children with allergic diseases, such as atopic dermatitis, asthma, and allergic rhinitis, were associated with exhibiting ADHD and ODD.

Read the abstract here

Practical guide to the management of ADHD

Fischer, B. & Herberholz, N. Paediatrics and Child Health. Published online: 5 August 2016

Image source: Ian Barbour – Flickr // CC BY-SA 2.0

Attention Deficit Hyperactivity Disorder (ADHD) manifests in persistent and pervasive inattention, hyperactivity and impulsivity, which interferes with functioning. It usually presents in childhood and can persist into adulthood. Severity, psychiatric co-morbidity, and parental psychopathology predict persistence. UK prevalence (ages 5–15 years) is 3.62% (boys) and 0.85% (girls) and the reported prevalence of children and young people on medication has increased over time. However, pharmacological treatment is not a solution in itself.

Read the abstract here

Attention deficit after kids’ critical illness linked to plasticizers in medical tubes

ScienceDaily, 1 April 2016


Children who are often hospitalized in intensive care units are more likely to have attention deficit disorders later, and new research finds a possible culprit: a high level of plastic-softening chemicals called phthalates circulating in the blood. The researchers, who will present their study results Friday at The Endocrine Society’s 98th annual meeting in Boston, suggest these chemicals, which are added to indwelling medical devices such as plastic tubes and catheters, seep into the child’s bloodstream.

Their study included 100 healthy children and 449 children who received treatment in a pediatric intensive care unit (PICU) and underwent neurocognitive testing four years later. Most of the PICU patients were recovering from heart surgery, but some had sustained accidental injuries or had severe infections. The researchers measured blood levels of DEHP metabolites, or byproducts. Initially they performed the blood tests in the healthy children and 228 of the patients while they were in the PICU. Patients had one to 12 medical tubes in the PICU and ranged in age from newborn to 16 years.

The investigators found that DEHP metabolite levels were not detectable in the blood samples of healthy children. However, at admission to the PICU, the critically ill children, already connected to catheters, had levels that Verstraete called “sky-high.” Although the DEHP levels decreased rapidly, they remained 18 times higher until discharge from the PICU compared with those of healthy children, he said.

Read the full commentary here