Stimulant Treatment In Children Research Articles

Enhancing spatial memory and pattern separation: Long-term effects of stimulant treatment in individuals with ADHD

This study explores the under-researched domain of long-term stimulant treatment in children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The necessity for extended treatment duration, often accompanied by safety concerns and side effects leading to treatment discontinuation, underscores the significance of this investigation. Concurrently, comparative studies have revealed adverse impacts on vulnerable regions within the hippocampal formation, accompanied by behavioral perturbations. We employed computerized tests and virtual reality to assess spatial memory, pattern separation, and object recognition memory in a cohort of children diagnosed with ADHD receiving stimulant treatment. We compared their performance to a group of neurotypical peers. Our findings indicate that the ADHD group exhibited a lower performance in spatial memory, pattern separation, and object recognition memory than ND group. Intriguingly, a positive relationship emerged between the duration of stimulant treatment and performance in these variables. Notably, this improvement was not immediate to MPH treatment but becomes significant after 24 months of treatment. In contrast to previous comparative investigations, our study did not reveal a detrimental impact on spatial navigation, object recognition memory, or pattern separation, despite the known interplay of these cognitive processes with the hippocampal formation. These results shed new light on the nuanced effects of stimulant treatment in ADHD, underscoring the need for a more comprehensive understanding of long-term treatment outcomes.

Is Stimulant Treatment in Children and Adolescents with Mood Dysregulation Associated with Adverse Outcomes?

The aim of this paper is to examine effects of stimulant treatment in children and adolescents with high levels of emotional dysregulation in a psychiatric outpatient clinic. Subjects were referred children and adolescents 6-17 years of age who presented to a child psychiatric outpatient clinic between September 2016-November 2021 and received a prescription for a stimulant medication. Children were stratified into those with low and high levels of emotional dysregulation as defined by an aggregate T-score of <180 or ≥210 on the combined Attention Problems, Aggressive Behavior, and Anxious/Depressed subscales of the Child Behavior Checklist (CBCL; CBCL-AAA). We analyzed patient prescription, diagnosis, and hospital visit data extracted from the electronic medical record from any time prior to referral through three months after referral. Patients with higher CBCL-AAA scores at clinic intake had a significantly different medication and diagnosis profile and were more likely to have a higher dosage of stimulants than patients with lower scores. These patients also were more likely to receive an additional medication class during follow-up, which was driven by second-generation antipsychotics (SGAs). Emergency room visits and inpatient psychiatric admissions were rare but present only in the group with higher CBCL-AA scores. These results suggest that stimulant treatment affects youth with high versus low levels of emotional dysregulation adversely with a need for higher stimulant doses and treatment augmentation with SGAs. The CBCL may be a useful tool for identifying poor outcomes with stimulant treatment.

Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for the development of substance abuse and substance use disorders (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment, and is associated with poor treatment outcomes. In this study, we provide a systematic review of controlled studies on the effectiveness of pharmacological, psychosocial, and complementary treatments of ADHD in adolescents with and without comorbid SUD. In addition, we review the longitudinal association between pharmacotherapy for childhood ADHD and the development of SUD in adolescence and early adulthood. We conducted a systematic review of the research literature published since 2000 using Medline, PsycINFO, and the Cochrane Database of Systematic Reviews databases to select randomized clinical trials, observational studies, and meta-analyses. The quality of the evidence from each study was rated using the SIGN grading system. Based on the limited evidence available, strong clinical recommendations are not justified, but provisionally, we conclude that stimulant treatment in children with ADHD may prevent the development of SUD in adolescence or young adulthood, that high-dose stimulant treatment could be an effective treatment for adolescents with ADHD and SUD comorbidity, that cognitive behavior therapy might have a small beneficial effect in these patients, and that alternative treatments are probably not effective. More studies are needed to draw definitive conclusions that will allow for strong clinical recommendations.

Stimulant Treatment Effect on Anxiety Domains in Children with Attention-Deficit/Hyperactivity Disorder With and Without Anxiety Disorders: A 12-Week Open-Label Prospective Study.

Objectives: The effect of stimulants on anxiety domains has not been systematically studied. We assessed prospectively the impact of stimulant treatment in children with attention-deficit/hyperactivity disorder (ADHD) on the severity of anxiety domains and on ADHD with comorbid anxiety disorders. Methods: Children with ADHD (n = 57, aged 6-15 years) started a stimulant or were switched from one stimulant to another. Assessments were conducted at four time points (baseline and weeks 2, 6, and 12) and consisted of parental questionnaires (ADHD rating scale, screen for child anxiety related disorders [SCARED]), and side effect questionnaire completed by a child psychiatrist. Results: A significant improvement in total SCARED scores was obtained after 12 weeks stimulant treatment in children both with and without anxiety disorders. Significant reductions were detected in generalized anxiety, separation anxiety, and school avoidance SCARED subscales, but not in panic and social anxiety subscales. ADHD symptoms significantly improved both in children with and without anxiety comorbidities. Conclusion: We found specific effects of stimulants on anxiety domains. Stimulant treatment, even for ADHD children diagnosed with comorbid anxiety disorders, is relatively safe regarding the risk of anxiety exacerbation. Moreover, the presence of anxiety symptoms or disorders does not interfere with the beneficial effect of the stimulants on the ADHD core symptoms. Clinical trial regestration number: IRB SMC-6893-20.

An innovative SMS intervention to improve adherence to stimulants in children with ADHD: Preliminary findings.

Although large datasets document that stimulants decrease the risk for many adverse ADHD-associated outcomes, compliance with stimulants remains poor. This study examined the effectiveness of a novel ADHD-centric text messaging-based intervention aimed to improve adherence to stimulant medications in children with ADHD. Subjects were 87 children aged 6-12, who were prescribed a stimulant medication for ADHD treatment. Prescribers gave permission to contact their patients for participation in the study. Subjects were primarily from the primary care setting with a subsample of psychiatrically referred subjects for comparison. Age- and sex-matched comparators were identified (3:1) from the same pool of prescriber-approved subjects that did not participate. Timely prescription refills (within 37 days) were determined from prescription dates documented in patients' electronic medical record. Eighty-five percent of SMS intervention patients refilled their prescriptions in a timely manner compared with 62% of patients receiving treatment as usual (OR = 3.46, 95% CI: 1.82, 6.58; p < 0.001). The number needed to treat statistic was computed as five, meaning for every five patients who receive the SMS intervention, we can keep one adherent to their stimulant treatment. These preliminary findings support the potential utility of a readily accessible technology to improve the poor rate of adherence to stimulant treatment in children with ADHD. To the best of our knowledge, this study is the first digital health intervention aimed at improving adherence to stimulant medication for children with ADHD. These results support the need for further examination of this technology through more definitive randomized clinical trials.

5.9 Opportunities and Challenges in Using a Mobile Health (mHealth) Intervention to Optimize Early Stimulant Treatment in Children With ADHD: Findings From the MH-2™ Pilot

ADHD is a very common (prevalence 4–12% of US children ages 4–17 years), chronic, debilitating, and costly neurodevelopmental illness. Efficacy of stimulants is well established, and the use of treatment guidelines is encouraged, but management of childhood ADHD remains poor, especially in community-based settings. Given near-universal access to smart phones in the United States, mobile health (mHealth) holds promise for improving quality of ADHD treatment in community-based settings. Pilot study was designed to evaluate the feasibility and acceptability of MH2TM, a web-based mobile health application (app) developed to optimize early stimulant treatment for children with ADHD.

ADHD Stimulant Treatment Does Not Affect Growth

To assess the long-term growth effect of stimulant treatment in children with attention-deficit/hyperactivity disorder (ADHD), researchers compared 243

Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study.

The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). We also aim to examine a possible dose-response relationship in such an association. We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health registers on psychiatric and somatic diagnoses, stimulant prescriptions, cardiovascular risk factors, pre- and perinatal and sociodemographic covariates in all children and their parents were merged, using the unique personal identification number. Hazard ratios (HR) for cardiovascular events were estimated using Cox regression, adjusted for other known risk factors. In the total population (n=714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR=1.83 (1.10-3.04). In children with ADHD (n=8300) stimulant treatment also increased the risk of a cardiovascular event (adjusted HR=2.20 [2.15-2.24]), with a complex time-dependent dose-response relationship. This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents, and it represents, to our knowledge, the longest prospective follow-up study. Cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total national population and in children with ADHD. We found a complex, time- and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. Our results suggest a safety signal with an increased risk of cardiovascular disease associated with stimulant treatment in children and adolescents, even after adjusting for a number of potential confounders.

The ADHD–Smoking Comorbidity and Implications for Stimulant Treatment in Children and Adolescents

The ADHD–Smoking Comorbidity and Implications for Stimulant Treatment in Children and Adolescents

Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study.

The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylphenidate, dexamphetamine, and atomoxetine in children and adolescents, within three diagnostic groups: 1) autism spectrum disorder (ASD), 2) attention-deficit/hyperactivity disorder (ADHD), and 3) other psychiatric disorders. Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 (n=852,711). Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylphenidate, dexamphetamine, and atomoxetine were extracted from the registers. Prescriptions were also stratified by duration (<6 months. vs.≥ 6 months). Sixteen percent of 9698 children and adolescents with ASD (n=1577), 61% of 11,553 children and adolescents with ADHD (n=7021) and 3% of 48,468 children and adolescents with other psychiatric disorders (n=1537) were treated with one or more ADHD medications. There was a significant increase in prescription rates of these medications for all three groups. From 2003 to 2010, youth 6-13 years of age with ASD, ADHD, and other psychiatric disorders had 4.7-fold (4.4-4.9), 6.3-fold (6.0-6.4), and 5.5-fold (5.0-5.9) increases, respectively, in prescription rates of ADHD medications. This is the largest study to date assessing stimulant treatment in children and adolescents with ASD, and is the first prospective study quantifying the change over time in the prevalence of treatment with ADHD medications in a population-based national cohort of children and adolescents with ASD. The prevalence of stimulant treatment in youth with ASD of 16% is consistent with earlier studies. The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark. This increase is not limited to only those with ADHD, but includes others with neuropsychiatric disorders, including ASD. The risks and benefits of this practice await further study.

Health-Related Quality of Life and Functional Outcomes from a Randomized, Controlled Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention Deficit Hyperactivity Disorder

BackgroundOptimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients’ symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.ObjectiveThe aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.MethodsPatients (aged 6–17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants’ parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome.ResultsThe full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p < 0.001) in Achievement, 1.079 (p < 0.001) in Risk Avoidance, 0.421 (p < 0.01) in Resilience and 0.365 (p < 0.05) in Satisfaction. In LDX-treated patients, placebo-adjusted improvements from baseline to endpoint in WFIRS-P scores were statistically significant (p < 0.001) for total score and four of the six domains, with effect sizes of 0.924 (total score), 1.249 (Learning and School), 0.730 (Family), 0.643 (Social Activities) and 0.640 (Risky Activities). OROS-MPH treatment showed similar patterns of improvement from baseline to endpoint in both CHIP-CE:PRF and WFIRS-P scores.ConclusionsBaseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.Electronic supplementary materialThe online version of this article (doi:10.1007/s40263-013-0095-5) contains supplementary material, which is available to authorized users.

PMH16 - Impact of atypical antipsychotic use on the persistence of the stimulant treatment in children and adolescents with attention deficit/hyperactivity disorder

PMH16 - Impact of atypical antipsychotic use on the persistence of the stimulant treatment in children and adolescents with attention deficit/hyperactivity disorder

Attention Deficit Hyperactivity Disorder Pharmacogenetics: The Dopamine Transporter and D4 Receptor

Attention Deficit Hyperactivity Disorder Pharmacogenetics: The Dopamine Transporter and D4 Receptor

Screening Children for Silent Cardiac Conditions

Whether to require electrocardiograms (ECGs) before beginning stimulant treatment in children with attention deficit hyperactivity disorder is

Stimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder Moderates Adolescent Academic Outcome

Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, the extent to which long-term academic gains are apparent in those having received such treatment remains elusive. This study examined prospectively the relationship of childhood stimulant treatment to academic functioning during adolescence. Children (n = 169) were initially recruited and diagnosed with ADHD when they were 7-11 years old. A subsample of those with childhood ADHD (n = 90) was reevaluated on average 9.13 (SD = 1.5) years later. Probands who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group (n = 80) on three subtests from the Wechsler Individual Achievement Test-II (WIAT-II), as well as high school grade point average (GPA) and number of retentions in school as derived from school records. Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that probands treated with psychostimulant medication achieved better academic outcomes, as measured by WIAT-II subtests and high school GPA, than those not treated with psychostimulants (p < .05). However, treated probands did not fare as well as the never-ADHD comparison group. Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance, although the extent of improvement is likely to vary as a function of multiple factors.

Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?

Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?

Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood.

Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders. The authors conducted a prospective longitudinal study of 176 methylphenidate-treated Caucasian male children (ages 6 to 12) with ADHD but without conduct disorder. The participants were followed up at late adolescence (mean age=18.4 years; retention rate=94%) and adulthood (mean age=25.3; retention rate=85%). One hundred seventy-eight comparison subjects also were included. All subjects were diagnosed by blinded clinicians. The Cox proportional hazards model included the following childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models tested for the following four lifetime outcomes: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, and stimulant use disorder. Other outcomes included antisocial personality, mood, and anxiety disorders. There was a significant positive relationship between age at treatment initiation and non-alcohol substance use disorder. None of the predictor variables accounted for this association. Post hoc analyses showed that the development of antisocial personality disorder explained the relationship between age at first methylphenidate treatment and later substance use disorder. Even when controlling for substance use disorder, age at stimulant treatment initiation was significantly and positively related to the later development of antisocial personality disorder. Age at first methylphenidate treatment was unrelated to mood and anxiety disorders. Early age at initiation of methylphenidate treatment in children with ADHD does not increase the risk for negative outcomes and may have beneficial long-term effects.

Modifiers of Long-Term School Outcomes for Children with Attention-Deficit/Hyperactivity Disorder: Does Treatment with Stimulant Medication Make a Difference? Results from a Population-Based Study

The purpose of this study was to describe the significance of potential modifiers of long-term school outcomes among children with attention-deficit/hyperactivity disorder (AD/HD), including treatment with stimulant medication. Subjects included 370 children with research-identified AD/HD from a 1976-1982 population-based birth cohort (N = 5718). In a companion study, the complete school record for each subject was reviewed to obtain information on reading achievement, absenteeism, grade retention, and school dropout. Data on type of stimulant, dose, age at initiation of treatment, and start/stop dates were collected from medical and school records, available for all subjects. Treatment with stimulants was associated with decreased rates of absenteeism; longer duration of treatment was also associated with decreased absenteeism rates. There was a modest positive correlation (r = .15, p = .012) between average daily stimulant dose and last reading score. Cases treated with stimulants were 1.8 times less likely to subsequently be retained a grade (95% confidence interval: 1.01-3.2; p = .047). The proportion of school dropout was similar between treated and not treated cases (22.2% vs 25.8%, p = .54). Other potential modifiers of school outcomes (sociodemographic risk factors, presence of comorbid learning or psychiatric disorders, and receipt of special educational services) were also examined and found to be associated with poorer outcomes. In this birth cohort, stimulant treatment of children with AD/HD was associated with improved reading achievement, decreased school absenteeism, and decreased grade retention. This study provides support for efforts to ensure that children with AD/HD receive appropriate long-term medical treatment.

Stimulants and Sudden Death: What Is a Physician to Do?

Recently, a US Food and Drug Administration advisory committee raised concerns about cardiovascular risks and sudden death in children and adolescents with attention-deficit/hyperactivity disorder who are receiving stimulants. We comment on the risk of sudden death in children/adolescents taking stimulants compared with population rates, biological plausibility, and known cardiovascular effects of stimulants to determine specific risk. There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign. There does not seem to be compelling findings of a medication-specific risk necessitating changes in our stimulant treatment of children and adolescents with attention-deficit/hyperactivity disorder. The use of existing guidelines on the use of stimulants (and psychotropic agents) may identify children, adolescents, and adults who are vulnerable to sudden death.

Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study.

To examine the impact of stimulant treatment during childhood and high school on risk for substance use, dependence, and abuse by young adulthood. A total of 147 clinic-referred hyperactive children were followed approximately 13 years into adulthood (mean: 21 years old; range: 19-25). At adolescent (age 15) and adult follow-up, probands were interviewed about their use of various substances and duration of stimulant treatment. Duration of stimulant treatment was not significantly associated with frequency of any form of drug use by young adulthood. Stimulant-treated children had no greater risk of ever trying drugs by adolescence or any significantly greater frequency of drug use by young adulthood. Stimulant treatment in high school also did not influence drug use in adulthood except for greater use of cocaine. This difference was no longer significant after controlling for severity of attention-deficit/hyperactivity disorder and conduct disorder in childhood, adolescence, and adulthood. Stimulant treatment in either childhood or high school was not associated with any greater risk for any formal Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised drug dependence or abuse disorders by adulthood. Treatment with stimulants did not increase the risk of ever having tried most illegal substances by adulthood except for cocaine. Subsequent analyses showed that this elevated risk was primarily mediated by severity of conduct disorder by young adulthood and not by stimulant treatment in childhood. This study concurs with 11 previous studies in finding no compelling evidence that stimulant treatment of children with attention-deficit/hyperactivity disorder leads to an increased risk for substance experimentation, use, dependence, or abuse by adulthood.