Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%-94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD. METHODS AND ANALYSIS: A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child's treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability. ETHICS AND DISSEMINATION: The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials. TRIAL REGISTRATION NUMBER: NCT04968522.

A critical review of the dextroamphetamine transdermal system for the treatment of ADHD in adults and pediatric patients.

INTRODUCTION: The dextroamphetamine transdermal system (d-ATS) is a stimulant patch recently approved by the United States (U.S.) Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD). AREAS COVERED: The composition of the d-ATS, pharmacokinetics, and metabolism are presented along with data from dermal trials evaluating the tolerability of patch application at various skin sites. Efficacy and safety data from a laboratory classroom study in children and adolescents including effect sizes are assessed. Pharmacokinetic-pharmacodynamic modeling of variable wear times is also discussed. EXPERT OPINION: Although stimulants are recommended as first-line treatment for ADHD in the U.S. some patients may have difficulty swallowing intact tablets and capsules, or dislike the taste or texture of chewable, oral disintegrating, or liquid formulations. The d-ATS fills an unmet need for those with ADHD who are unable or prefer not to take medication orally. Varying wear time of the d-ATS also gives flexibility in length of stimulant effect which may be useful for patients with changing schedules. However, dermal discomfort must be considered in addition to the usual amphetamine side effects when prescribing the d-ATS. Patient and provider experience will determine how frequent the use of d-ATS becomes.

Switch to Lisdexamfetamine in the Treatment of Attention-Deficit Disorder at a Psychiatric Outpatient Clinic for School-Aged Children: A Danish Cohort Study.

Objectives: This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. Results: One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). Implications: The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.

Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.

Importance: Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients. Objective: To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD. Design, Setting, and Participants: This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023. Exposure: Use of specific ADHD medications. Main Outcomes and Measures: The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models. Results: A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92). Conclusions and Relevance: In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.

Changes in real-world dispensing of ADHD stimulants in youth from 2019 to 2021 in California.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric neurobehavioral disorders in the U.S. Stimulants, classified as controlled substances, are commonly used for ADHD management. We conducted an analysis of real-world stimulants dispensing data to evaluate the pandemic's impact on young patients (≤ 26 years) in California. Methods: Annual prevalence of patients on stimulants per capita across various California counties from 2019 and 2021 were analyzed and further compared across different years, sexes, and age groups. New patients initiating simulants therapy were also examined. A case study was conducted to determine the impact of socioeconomic status on patient prevalence within different quintiles in Los Angeles County using patient zip codes. Logistic regression analysis using R Project was employed to determine demographic factors associated with concurrent use of stimulants with other controlled substances. Results: There was a notable reduction in prevalence of patients ≤26 years old on stimulants during and after the pandemic per 100,000 people (777 in 2019; 743 in 2020; 751 in 2021). These decreases were more evident among the elementary and adolescent age groups. The most prevalent age group on stimulants were adolescents (12-17 years) irrespective of the pandemic. A significant rise in the number of female patients using stimulants was observed, increasing from 107,957 (35.2%) in 2019 to 121,241 (41.1%) in 2021. New patients initiating stimulants rose from 102,754 in 2020 to 106,660 in 2021, with 33.2% being young adults. In Los Angeles County, there was an increasing trend in patient prevalence from Q1 to Q5 income quintiles among patients ≥6 years. Consistently each year, the highest average income quintile exhibited the highest per capita prevalence. Age was associated with higher risk of concurrent use of benzodiazepines (OR, 1.198 [95% CI, 1.195-1.201], p < 0.0001) and opioids (OR, 1.132 [95% CI, 1.130-1.134], p < 0.0001) with stimulants. Discussion: Our study provides real-world information on dispensing of ADHD stimulants in California youth from 2019 to 2021. The results underscore the importance of optimizing evidence-based ADHD management in pediatric patients and young adults to mitigate disparities in the use of stimulants.

Attention deficit and hyperactivity disorder and use of psychostimulants in Aotearoa, New Zealand: exploring the treatment gap.

Introduction Attention deficit and hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting about 7% of those aged up to 12 years, 5% of teenagers and 3% of adults. It is associated with poor academic performance, substance abuse, criminality, poor social functioning and other negative outcomes. Psychotherapeutic treatment is moderately successful, whereas pharmacotherapy with stimulant medication is more efficacious and is recommended in many international guidelines. Anecdotal evidence suggests underuse of these medications in Aotearoa, New Zealand. Aim To estimate how many patients with ADHD are prescribed psychostimulants in Aotearoa, New Zealand. Methods National prescribing data for dexamphetamine and methylphenidate in 2022 were obtained and matched against estimated prevalence of ADHD by age. Results There is a significant treatment gap for which inability to access first-line medication is likely to be the predominant explanation. Discussion The data suggest failure of our health system to provide reasonable health care for a significant number of people with ADHD, and results in inequity in outcomes. New approaches are needed that will increase access to first-line medication, yet maintain appropriateness of diagnosis and limit risk of medication diversion.

Safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder: A systematic review and network meta-analysis.

OBJECTIVE: To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHODS: Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1. RESULTS: 48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners' parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners' teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42). CONCLUSION: The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings.

Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis.

The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support.

Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period.

BACKGROUND: An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described. OBJECTIVE: This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories. METHODS: The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups. RESULTS: Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%). CONCLUSION: We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.

Bidirectional associations between mental disorders, antidepressants and cardiovascular disease.

BACKGROUND: Mental disorders have a high comorbidity with cardiovascular disease (CVD), but the causality between them has not been fully appreciated. OBJECTIVE: This study aimed to systematically explore the bidirectional causality between the two broad categories of diseases. METHODS: We conducted Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to evaluate potential causal links between 10 mental disorders, the use of antidepressants and 7 CVDs. FINDINGS: We discovered that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and insomnia exhibit connections with elevated risks of two or more CVDs. Moreover, the use of antidepressants is linked to heightened risks of each CVD. Each distinct CVD is correlated with a greater probability of taking antidepressants. Our MVMR analysis demonstrated that the use of antidepressants is correlated with the elevation of respective risks across all cardiovascular conditions. This includes arrhythmias (OR: 1.28), atrial fibrillation (OR: 1.44), coronary artery disease (OR: 1.16), hypertension (OR: 1.16), heart failure (OR: 1.16), stroke (OR: 1.44) and entire CVD group (OR: 1.35). However, MDD itself was not linked to a heightened risk of any CVD. CONCLUSIONS: The findings of our study indicate that MDD, insomnia and ADHD may increase the risk of CVD. Our findings highlight the utilisation of antidepressants as an independent risk factor for CVD, thus explaining the influence of MDD on CVD through the mediating effects of antidepressants. CLINICAL IMPLICATIONS: When treating patients with antidepressants, it is necessary to take into consideration the potential beneficial and detrimental effects of antidepressants.

Childhood attention-deficit hyperactivity disorder: socioeconomic inequalities in symptoms, impact, diagnosis and medication.

BACKGROUND: Children from disadvantaged backgrounds are at greater risk of attention-deficit hyperactivity disorder (ADHD)-related symptoms, being diagnosed with ADHD, and being prescribed ADHD medications. We aimed to examine how inequalities manifest across the 'patient journey', from perceptions of impacts of ADHD symptoms on daily life, to the propensity to seek and receive a diagnosis and treatment. METHODS: We investigated four 'stages': (1) symptoms, (2) caregiver perception of impact, (3) diagnosis and (4) medication, in two data sets: UK Millennium Cohort Study (MCS, analytic n ~ 9,000), with relevant (parent-reported) information on all four stages (until 14 years); and a population-wide 'administrative cohort', which includes symptoms (child health checks) and prescriptions (dispensing records), born in Scotland, 2010-2012 (analytic n ~ 100,000), until ~6 years. We described inequalities according to maternal occupational status, with percentages and relative indices of inequality (RII). RESULTS: The prevalence of ADHD symptoms and medication receipt was considerably higher in the least compared to the most advantaged children in the administrative cohort (RIIs of 5.9 [5.5-6.4] and 8.1 [4.2-15.6]) and the MCS (3.08 [2.68-3.55], 3.75 [2.21-6.36]). MCS analyses highlighted complexities between these two stages, however, those from least advantaged backgrounds, with ADHD symptoms, were the least likely to perceive impacts on daily life (15.7% vs. average 19.5%) and to progress from diagnosis to medication (44.1% vs. average 72.5%). CONCLUSIONS: Despite large inequalities in ADHD symptoms and medication, parents from the least advantaged backgrounds were less likely to report impacts of ADHD symptoms on daily life, and their children were less likely to have received medication postdiagnosis, highlighting how patient journeys differed according to socioeconomic circumstances.

Novel pharmacological targets for GABAergic dysfunction in ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopment disorder that affects approximately 5% of the population. The disorder is characterized by impulsivity, hyperactivity, and deficits in attention and cognition, although symptoms vary across patients due to the heterogenous and polygenic nature of the disorder. Stimulant medications are the standard of care treatment for ADHD patients, and their effectiveness has led to the dopaminergic hypothesis of ADHD in which deficits in dopaminergic signaling, especially in cortical brain regions, mechanistically underly ADHD pathophysiology. Despite their effectiveness in many individuals, almost one-third of patients do not respond to stimulant treatments and the long-term negative side effects of these medications remain unclear. Emerging clinical evidence is beginning to highlight an important role of dysregulated excitatory/inhibitory (E/I) balance in ADHD. These deficits in E/I balance are related to functional abnormalities in glutamate and Gamma-Aminobutyric Acid (GABA) signaling in the brain, with increasing emphasis placed on GABAergic interneurons driving specific aspects of ADHD pathophysiology. Recent genome-wide association studies (GWAS) have also highlighted how genes associated with GABA function are mutated in human populations with ADHD, resulting in the generation of several new genetic mouse models of ADHD. This review will discuss how GABAergic dysfunction underlies ADHD pathophysiology, and how specific receptors/proteins related to GABAergic interneuron dysfunction may be pharmacologically targeted to treat ADHD in subpopulations with specific comorbidities and symptom domains. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Guanfacine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents with Down Syndrome: A Retrospective Chart Review.

Study Design: Retrospective case series. Objectives: The objective of this study was to provide naturalistic data on the use of guanfacine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in a clinically referred sample of youth with Down syndrome (DS). Methods: The medical records of children and adolescents with DS who received guanfacine for the treatment of ADHD from a multidisciplinary neurodevelopmental disorder clinic between September 1, 2011, and September 10, 2021, were reviewed. Demographic and clinical characteristics, guanfacine dose and treatment duration, and adverse effects were recorded. Clinical Global Impression Scale (CGI) scores for ADHD symptom severity (S) and improvement (I) were retrospectively assigned by a child and adolescent psychiatrist based on review of the clinic notes. Response to guanfacine was defined as completion of at least 12 weeks of treatment and a Clinical Global Impression Improvement subscale rating ≤2 (1 = "very much improved" or 2 = "much improved"). Results: Twenty-one patients were eligible for inclusion, of whom 17 (81%) completed at least 12 weeks of guanfacine. Ten of the 21 patients (48%; 95% confidence interval [CI]: 28%-68%) responded to treatment. The median time on guanfacine treatment covered by the clinic notes was 50.4 weeks, with a range of 0.3 weeks to 7.5 years. Thirteen patients (62%) remained on guanfacine at the time of their most recent clinic note. Nine patients had adverse events documented in their clinic notes (43%; 95% CI: 24%-63%), most commonly sleepiness (n = 7) and constipation (n = 2). Conclusion: About half of patients with DS responded to guanfacine for the treatment of ADHD and many tolerated long-term use. Study limitations primarily relate to the retrospective nature of the study and small sample size.

Stimulant prodrugs: A pharmacological and clinical assessment of their role in treating ADHD and binge-eating disorder.

In this review, we critically evaluate the contribution of prodrugs to treating two related psychiatric disorders, attention-deficit hyperactivity disorder (ADHD) and binge-eating disorder (BED). ADHD is characterized by inattentiveness, distractibility, impulsiveness, and hyperactivity. BED is also an impulse-control disorder which leads to frequent, compulsive episodes of excessive eating (binges). Lisdexamfetamine (LDX; prodrug of d-amphetamine) is approved to treat both ADHD and BED. Serdexmethylphenidate (SDX; prodrug of d-threo-methylphenidate) is not clinically approved as monotherapy but, in a fixed-dose combination with immediate release d-threo-methylphenidate (Azstarys™), SDX is approved for managing ADHD in children/adolescents. The pharmacological actions of a stimulant mediate both its efficacy and side-effects. Therefore, daily management of ADHD or BED to maintain optimum efficacy and tolerability places highly restrictive requirements on the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of stimulant medications, especially prodrugs. Prodrugs must have good bioavailability and rapid metabolism to provide therapeutic efficacy soon after morning dosing combined with providing stimulant coverage throughout the day/evening. A wide selection of dosages and linear PK for the prodrug and its active metabolite are essential requirements for treatment of these conditions. The proposed neurobiological causes of ADHD and BED are described. The chemical, pharmacological and PK/PD properties responsible for the therapeutic actions of the prodrugs, LDX and SDX, are compared and contrasted. Finally, we critically assess their contribution as ADHD and BED medications, including advantages over their respective active metabolites, d-amphetamine and d-threo-methylphenidate, and also their potential for misuse and abuse.

Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part I.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of attention-deficit/hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive-compulsive disorder and related disorders, and tic disorder. Pitfalls in the treatment of other disorders are addressed in a separate paper (part II).

ADHD prescription patterns and medication adherence in children and adolescents during the COVID-19 pandemic in an urban academic setting.

BACKGROUND: COVID-19 impacted all students, especially those with attention deficit hyperactivity disorder (ADHD), putting them at risk for disruption to their medication regimen and school performance. Our study aimed to identify if ADHD medication regimens were disrupted through analyzing prescription refills and if telehealth management demonstrated a higher rate of adherence. METHODS: A total of 396 patients from the General Academic Pediatrics (GAP) clinic at Children's Hospital of The King's Daughters (CHKD) were included in the study. Patients were between the ages of 8-18 with a history of ADHD for three or more years that was medically managed with four or more prescription refills between January 2019 and May 2022. A retrospective chart review collected age, sex, race, refill schedule, appointment schedule, and number of telehealth appointments. Data analysis compared the variables and defined "pre-pandemic months" as January 2019 through March 2020 and "pandemic months" as April 2020 through June 2022. RESULTS: The total percentage of patients who had their ADHD medications during pre-pandemic months ranged from 40 to 66% versus 31-44% during pandemic months. Additionally, the total percentage of patients who had quarterly ADHD management appointments during pre-pandemic months ranged between 59 and 70% versus 33-50% during pandemic months. The number of months with ADHD prescription refills over the last three years was significantly higher among those who had both virtual and in-person visits than those who had just in-person visits, p < 0.001. Regarding race, Black patients had a lower number of medication refills compared to White patients when controlled for appointment type. They also had a lower number of total appointments, but there was not a significant difference in the number of virtual appointments. CONCLUSIONS: Since the start of the pandemic, ADHD patients have both refilled their prescriptions and returned to clinic less frequently. This data suggests a need to re-evaluate the ADHD symptoms of GAP patients periodically and return them to a more consistent medication regimen. Telehealth appointments are a potential solution to increase adherence. However, racial inequities found in this study need to be addressed.