Pharmacological Treatment Of Children Research Articles

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

Factors associated with pharmacological treatment in children with attention-deficit/hyperactivity disorders: a retrospective study of a series of 77 cases in a single third-level reference Centre in Apulia region

BackgroundThe present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients.MethodsSeventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used.ResultsPharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40).ConclusionsThis study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.

Pharmacological Treatment of Children and Adolescents Diagnosed with Attention-deficit/hyperactivity Disorder at Mental Health Services in Qatar: A Retrospective Study

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children. The consequences of ADHD could seriously impact the patient’s life, and thus parental training, behavioral therapies, and pharmacological interventions are the main therapeutic options applied. This study was conducted to explore the trends of prescribing pharmacological medications used in ADHD and identify the reasons for discontinuation of such medications. Methodology: A retrospective chart review for patients diagnosed with ADHD at Child and Adolescent Mental Health Services (CAMHS) in Qatar from January 2019 to December 2019 was carried out. Patients less than 18 years old, diagnosed with ADHD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and were on pharmacological treatment for ADHD were suitable to be included. Patients who were not on anti-ADHD medications were excluded from the study. Results: Ninety-two patients were eligible to be included in the study. Autism Spectrum Disorder (ASD) was found to be the most coexisting condition in addition to ADHD in 16.3%. Methylphenidate was the most prescribed medication (68.5%), followed by atomoxetine (30.4%). None of the participants were found on modafinil, guanfacine, bupropion, or benzodiazepines, and none exceeded the maximum licensed dose of either methylphenidate or atomoxetine. Half (50%) of the sample on atomoxetine discontinued treatment compared to 14.2% in the methylphenidate group. Conclusion: The clinical practice of prescribing pharmacological options for ADHD was thoroughly in alignment with international guidelines. The effects of long-term use of these psychotropics in this particular group of patients on their neurobiological, behavioral, and physical health should be studied further.

Pharmacological treatment of children with ADHD: how educators persuade parents to use it

ABSTRACT Educators are key in advising doctors and parents on whether to medicate pupils with attention deficit hyperactivity disorder (ADHD). Here, using a semi-structured in-depth interview and grounded theory, we ask how 138 Israeli teachers and headmasters perceive their role in parents’ decisions to medicate. Generally, teachers refrain from persuading parents to use medication and some even talk them out of it. There is, however, a gradual escalation in educators’ attitudes towards persuading parents to medicate when educators consider the difficulties flowing from ADHD. When these difficulties find expression mainly in pupils’ achievements, persuasion is usually indirect, manifested in hints to parents about the need to medicate. When problematic if not violent behaviour manifests, stronger persuasive tactics are used, such as summoning parents to meetings and suspending pupils. Many educators do not regard these sanctions against parents who resist medicating their children as unfair pressure but do admit that they are meant to persuade parents to allow medication. Thus, Israeli educators send a bivalent message. The system’s approach explicitly upholds parents’ right to decide on their own. The other voice is manifested in de facto policy, especially when the behaviour of the pupil with ADHD is improper.

COVID-19 treatment of pediatric cases: Advantages vs disadvantages

COVID-19 became the most challenging health, economic, and social problem of the entire world from the beginning of 2020. Despite the first insight about COVID-19 in children, more critical involvement of children was observed. However, World Health Organization has not approved any preventive drug or curative antibiotic for COVID-19 infection [1], and reports on COVID-19 pharmacological treatment in children are limited. Pediatricians have concerns about the effect of common pharmacological treatments of COVID-19 in pediatric cases. Safety and efficacy of pharmacological treatments in hospitalized children are controversial.

Clinical characteristics of children and adolescents with ADHD with or without methylphenidate prescription at their first diagnostic assessment.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD.

Efficacy and Safety of Lurasidone in Children and Adolescents: Recommendations for Clinical Management and Future Research.

Lurasidone is a novel azapirone derivative and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5- HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acted on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Administered with food or within 30 minutes from a meal, it presents sufficient bioavailability and does not interact with most of the other drugs during metabolism. With little effects on hormones and weight gain, potential procognitive profile due to its 5-HT7 antagonism, and reduced extrapyramidal side effects, lurasidone could be a good choice in terms of both effectiveness and tolerability, particularly for patients headed towards a long-term treatment. This article aims to summarize the available scientific evidence from the literature on the use of lurasidone in children and adolescents and to provide recommendations for clinical management and future research.

Efficacy of ibuprofen in musculoskeletal post-traumatic pain in children: A systematic review.

Musculoskeletal (MSK) injuries are one of the most frequent reason for pain-related evaluation in the emergency department (ED) in children. There is still no consensus as to what constitutes the best analgesic for MSK pain in children. However, ibuprofen is reported to be the most commonly prescribed analgesic and is considered the standard first-line treatment for MSK injury pain in children, even if it is argued that it provides inadequate relief for many patients. The purpose of this study was to review the most recent literature to assess the efficacy of ibuprofen for pain relief in MSK injuries in children evaluated in the ED. We performed a systematic review of randomized controlled trials on pharmacological interventions in children and adolescents under 19 years of age with MSK injuries according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the risk ratio for successful reduction in pain scores. Six studies met the inclusion criteria and provided data on 1028 children. A meta-analysis was not performed since studies were not comparable due to the different analgesic treatment used. No significant difference in term of main pain score reduction between all the analgesics used in the included studies was noted. Patients who received oral opioids had side effects more frequently when compared to children who received ibuprofen. The combination of effect on pain relief and tolerability would suggest ibuprofen as the initial drug of choice in providing relief from mild-to-moderate MSK pain in children in the ED. The results obtained in this review and current research suggest that there’s no straightforward statistically significant evidence of the optimal analgesic agent to be used. However, ibuprofen may be preferable as the initial drug of choice in providing relief from MSK pain due to the favorable combination of effectiveness and safety profile. In fact, despite the non-significant pain reduction as compared to children who received opioids, there are less side effect associated to ibuprofen within studies. The wide range of primary outcomes measured in respect of pain scores and timing of recorded measures warrants a future standardization of study designs.

Dog-Assisted Therapy for Children and Adolescents With Fetal Alcohol Spectrum Disorders a Randomized Controlled Pilot Study.

ObjectiveThe rationale of this study was to evaluate the efficacy of dog-assisted therapy (DAT) combined with pharmacological treatment in children and adolescents with fetal alcohol spectrum disorder (FASD).MethodWe conducted a randomized, rater-blinded, controlled pilot trial in a cohort of 33 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 17) or Treatment as Usual (TAU control group) (n = 16).ResultsOf the initial 39 participants enrolled, 33 completed treatment. A mixed-effects model analysis revealed that participants who were assigned to the DAT group experienced significantly improvements on social skills (SSIS-P social skills: p = 0.02, d = 0.8), reductions on externalizing symptoms (CBCL externalizing: p = 0.03; d = 0.56), and lower scores on FASD severity (CGI-S clinician: p = 0.001, d = 0.5).ConclusionDAT is a promising adjunctive treatment for children and adolescents with FASD.Clinical Trial RegistrationDog-assisted therapy for children and adolescents with fetal alcohol spectrum disorders: a randomized controlled pilot study; http://clinicaltrials.gov/, identifier NCT04038164.

Long-term effects of theta/beta neurofeedback on EEG power spectra in children with attention deficit hyperactivity disorder

ObjectiveNeurofeedback has been proposed as an effective alternative for pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD), with potentially long-term and delayed benefits. However, the specificity of such long-term behavioral improvements remains inconclusive and therefore additional research into the neurophysiological effects of neurofeedback is needed. We compared long-term effects of theta/beta neurofeedback (NFB) to methylphenidate (MPH) and physical activity (PA, semi-active control intervention) on electroencephalogram (EEG) power spectra. Based on the vigilance stabilization model, we hypothesized further reductions in theta and alpha power in the NFB compared to the control groups. MethodEEG power spectra (theta, alpha and beta) during resting and task conditions were recorded at pre-, post-intervention and 6-months follow-up in 67 children, aged 7–13 (NFB: n = 24, MPH: n = 23, or PA: n = 20). ResultsAnalyses revealed no power spectra differences at follow-up between MPH and NFB (range p = .165–.905) and PA and NFB (range p = .172–.822). ConclusionsNo evidence was found for the specificity of theta/beta NFB at follow-up. SignificanceThis was the first study into long-term neurophysiological effects of theta/beta NFB. Future studies are encouraged to explore both specific and non-specific mechanisms of NFB.Clinical trials registration: Train Your Brain? Exercise and neurofeedback intervention for ADHD, https://clinicaltrials.gov/show/NCT01363544, Ref. No. NCT01363544.

What are the benefits and harms of pharmacological treatments for children with comorbid tic disorders?

What are the benefits and harms of pharmacological treatments for children with comorbid tic disorders?

Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

Approach to Optimize Pharmacological Treatment in Children.

Approach to Optimize Pharmacological Treatment in Children.

Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm.

Pharmacologic treatment of children and adolescents with inflammatory bowel diseases (IBD) [Crohn's disease and ulcerative colitis] requires consideration of disease and medication effects on growth and nutrition, the importance of durability of biologics, and concerns for long-term sequelae of disease and therapies. Achieving early remission in children with Crohn's disease correlates with improved outcomes and therefore allows a window of opportunity for maximizing growth. Thus, there is a great need to treat children and adolescents with the right drug at the right time while achieving adequate exposure. Improved understanding of disease phenotypes, disease natural history, and risk stratification will play a critical role in treatment selection for children, particularly as more therapeutic options become available. Here we summarize data supporting newer concepts of treating the individual child with IBD through targeted early biologic treatment, including utilization of therapeutic drug monitoring to optimize treatment effects and the use of early antitumor necrosis factor (TNF)-α therapies to mitigate long-term sequelae of the disease. Recent inception cohort studies provide important data regarding the risk stratification of children and adolescents with IBD, which support a move toward a personalized therapeutic approach to IBD in children and adolescents.

M86 - INTEGRATIVE GENOMIC ANALYSIS OF METHYLPHENIDATE RESPONSE IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

Background Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with Attention-Deficit Hyperactivity Disorder (ADHD). However, a considerable interindividual variability exists in clinical response, which may reflect underlying genetic influences. Methods We performed a Genome-Wide Association Study (GWAS) of MPH efficacy in 173 ADHD pediatric patients, considering the Clinical Global Impression-Improvement scale as the primary outcome measure of treatment success. For subsequent analyses, we prioritized the Single-Nucleotide Polymorphisms (SNPs) with P-values below 0.05 on the GWAS based on functional annotation and expression quantitative trait loci (eQTL) analysis in human brain. Ingenuity Pathway Analysis was used to assess the biological functions and pathways related to genes containing at least one SNP nominally associated with both MPH response and human cortical expression levels (eSNPs), and to test for over-representation of genes previously studied in either ADHD or treatment outcome. We subsequently meta-analyzed the association between clinical response and the eSNPs identified across the discovery sample and an independent cohort of 189 ADHD adult patients. Results Although no variant reached genome-wide significance, the set of genes containing SNPs nominally associated with MPH response was significantly enriched for genes previously studied in ADHD or treatment outcome (Padjusted=1.56e-31). Considering these results, we prioritized the nominally significant markers by functional annotation and eQTL analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (eGenes). Pathway enrichment analyses revealed an over-representation (Padjusted Discussion To our knowledge, this is the first study investigating the genetic basis of MPH response from an integrative perspective that combines GWAS data, functional annotation, eQTL in relevant tissues to ADHD and pathway enrichment analyses. Our results highlight genes related to nervous system development and function, neurological diseases and psychological disorders. Thus, this comprehensive strategy provides a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggests promising candidates that may contribute to clinical outcome.

Treatment of pediatric restless legs syndrome.

Restless legs syndrome (RLS) is not uncommon in children with an estimated prevalence of 2%. There is clear evidence that RLS affects quality of life, sleep, cognition and behavior in children and adults. Although the diagnosis of RLS can be challenging in young children, the International Restless Legs Study Group (IRLSSG) has published guidelines for diagnosis which include description of symptoms in the child's own words. Once the diagnosis is made, treatment options must be explored. It is commonly accepted that non-pharmacological interventions be recommended to all affected families. These include maintaining a consistent bedtime routine, establishing healthy eating habits and exercise, avoiding caffeine and other substances that can exacerbate RLS, and stretching before bedtime. Pharmacological interventions in children are challenged by the lack of solid data supporting effectiveness and long-term safety. Historically and based on pathophysiology, iron supplementation is the first line therapy in children. Recently intravenous iron supplementation has shown promising results, following studies in adults. Most studies in children on various pharmacological options follow a robust body of data previously published in adult patient with RLS, yet data in children remain scarce. This chapter will discuss both non-pharmacologic and pharmacologic treatment options for children with RLS.

Neurocognitive assessment of children with neurodevelopmental disorders: Preliminary findings.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and hyperactivity/impulsivity, and is often treated pharmacologically. It is necessary to use both subjective and objective assessments to diagnose and determine the efficacy of pharmacological treatment in children with ADHD, but cognitive assessment tools for ADHD are scarce. We examined a computer-administered, brief, and repeatable cognitive assessment tool: CogHealth. The aims of this study were to use the CogHealth battery, an objective assessment tool, to compare cognitive function between children with ADHD or ADHD + autism spectrum disorder (ASD) and healthy children and to assess improvements in cognitive function following pharmacological treatment. We measured the cognitive function of nine children with ADHD or ADHD + ASD using CogHealth and compared the results with those of 33 age-matched children from the community. Cognitive function comparisons were made before and after psychostimulant treatment with methylphenidate. We detected significant cognitive abnormalities in the children with ADHD, compared with the control subjects. The children with pre-treatment ADHD had significantly more errors on the detection task (DT), and more anticipatory errors in the one card learning task, compared with control children. The children with ADHD significantly improved their accuracy on the one back test (OBT), and had significantly fewer errors, anticipatory errors, and shorter reaction times after osmotic-release oral system methylphenidate treatment. The DT is a useful neurocognitive function assessment for children with ADHD, and the OBT can measure pharmacological treatment effectiveness in children with ADHD.

Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies.

Graves' disease in children in the two decades following implementation of an iodine prophylaxis programme.

Grave’s disease (GD) is a form of thyroid autoimmune disease characterised by hyperthyroidism. It is a rare clinical problem in paediatrics. Development of disease is the result of genetic susceptibility and some environmental factors. One of the best-documented environmental factors involved in thyroid autoimmunity is iodine excess. The aim of our study was to analyse the clinical course and response to pharmacological treatment in children diagnosed with Graves’ disease in first two decades after mandatory salt iodination. Records of 94 children diagnosed with GD in the years 1998-2017 were analysed. Medical data of patients was compared between two decades following implementation of iodine prophylaxis: 1998-2007 (first-decade group – FDG) and 2008-2017 (second-decade group – SDG); 34 and 60 patients, respectively. Medical data of FDG was obtained from archival records and previous analysis performed in 2006. Data of 60 patients from SDG were obtained from currently available medical records. Results were statistically analysed using Microsoft Excel and Statistica 11 software. Results: In our study, after mandatory salt iodination, the tendency of an increase in newly diagnosed GD in children without family susceptibility was observed. The antibody profile indicates the significant contribution of the autoimmune process involving all thyroid antigens; therefore, the term “autoimmune hyperthyroidism” seems to be more appropriate than classical GD in this group of patients. The first-choice treatment with methimazole rarely causes adverse events during the therapy, and they have benign character.

Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis

IntroductionAlthough previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain...