Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

The Use of Methylphenidate During Inpatient Rehabilitation After Pediatric Traumatic Brain Injury: Population Characteristics and Prescribing Patterns.

OBJECTIVE: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. SETTING: Inpatient pediatric rehabilitation. PARTICIPANTS: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. DESIGN: Multicenter, retrospective medical record review. MAIN MEASURES: Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). RESULTS: Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. CONCLUSION: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.

Adults with both bipolar disorder and ADHD.

ADHD and bipolar disorder (BP) commonly coexist, and both share key symptoms, depending on affective state and emotional dysregulation. The overlap poses diagnostic challenges and may lead to underdiagnoses. Comorbid cases exhibit worsened symptom burden, increased psychiatric morbidity, admissions, and suicide attempts. Treating BP before ADHD is recommended. Stimulant use combined with mood stabilisers may be effective and relatively safe; however, this review finds that well-designed randomised controlled studies in the area is warranted.

Dispensing of attention-deficit hyperactivity disorder medications for adults in Aotearoa New Zealand.

AIM: To report dispensing trends for attention-deficit hyperactivity disorder (ADHD) in Aotearoa New Zealand, focussing on adults in order to highlight increasing demand for ADHD treatment by adults and to prompt discussion. METHOD: Demographic and dispensing data for ADHD were obtained from the Pharmaceutical Collection between the years 2006 and 2022. This was stratified according to child (<18 years) and adult (≥18 years) populations. Population dispensing rates for methylphenidate and atomoxetine were calculated. Key findings are reported to reveal demographic and dispensing trends for medication treated ADHD in Aotearoa New Zealand. RESULTS: More males are dispensed ADHD medication than females, although this is less evident for adults (54.8% male). Maori adults are dispensed ADHD medication at a lower rate (10.1%) than Maori children (22.9%). There was a 10-fold increase in dispensing of ADHD medication for adults compared to a three-fold increase for children over the study period. New dispensing for adults doubled between 2011 and 2022. CONCLUSION: Medication treatment for adult ADHD is increasing in Aotearoa New Zealand and includes treatment for persisting childhood ADHD and new diagnoses made in adulthood. Despite increases, dispensing rates for ADHD remain lower than prevalence estimates, suggesting a significant treatment gap. Addressing the treatment gap for ADHD may reduce negative effects of ADHD, but wider social influences should also be considered.

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.

Stigma Related to the Non-Medical Use and Diversion of Prescription Stimulant Drugs: Should We Care.

BACKGROUND: Non-medical use (NMU) and diversion of prescription stimulants are prevalent on college campuses. Diversion represents a primary source of acquisition for NMU among young adults. This study examined relationships between stigmatizing beliefs related to NMU and diversion of stimulant medications and engagement in these behaviors, as well as how such perceptions are associated with indicators of psychological distress among those who engage in these behaviors. METHODS: Young adults (N = 384) were recruited from a large US university to participate in this cross-sectional electronic survey-based study. Relationships between stigma variables and NMU and diversion were assessed. Among those who engage in NMU and diversion, we tested relationships between stigma variables and indicators of psychological distress, using validated instruments. RESULTS: Perceived social and personal stigmatic beliefs did not significantly predict NMU. However, perceived social and personal stigma of diversion significantly reduced diversion likelihood. For NMU, associations were found between stigma variables and indicators of psychological distress. Markedly, we found that as stigmatic perceptions of NMU increased, so did depressive, anxiolytic, and suicidal symptomatology among those who engage in NMU. CONCLUSIONS: Stigmatization does not deter NMU; however, stigmatization is positively associated with psychological harm among those who engage in NMU. Interventions should be developed to reduce stigmatization in order to improve psychological health among those who engage in NMU. Stigmatic perceptions of diversion were not predictive of psychological harm, though they are negatively associated with diversion behavior.

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.

[Wakefulness-promoting agents for severe fatigue: to use or not to use?] / Medicatie tegen ernstige aanhoudende vermoeidheid.

About 20% of adults experience excessive daytime sleepiness or severe fatigue. Causes include somatic conditions, psychiatric disorders, and medication or drug use. Treatment depends on the underlying cause. If sleepiness persists despite optimal treatment of the underlying condition, exclusion of other causes, and behavioral interventions, wakefulness-promoting agents may be considered. However, no established pharmacological strategy exists for symptomatic treatment. Modafinil and stimulants like methylphenidate may offer some benefit based on experiences with narcolepsy or idiopathic hypersomnia. Studies in specific patient groups (e.g., multiple sclerosis, Parkinson's disease, traumatic brain injury, cancer-related fatigue) show variable results. The use of wakefulness-promoting agents is discouraged for addressing unexplained fatigue, as seen in the context of chronic fatigue syndrome.

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.

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.

ADHD Pharmacotherapy and Mortality in Individuals With ADHD.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. Objective: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. Design, Setting, and Participants: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. Exposures: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. Main Outcomes and Measures: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Results: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Conclusions and Relevance: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Viloxazine extended-release capsules as an emerging treatment for attention-deficit/hyperactivity disorder in children and adolescents.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention and/or hyperactivity and impulsivity. Viloxazine extended-release (ER) capsules (Qelbree®) is a US Food and Drug Administration-approved nonstimulant treatment option for children, adolescents, and adults with ADHD. AREAS COVERED: This review manuscript summarizes the neurobiology of ADHD and currently available treatment options before discussing viloxazine pharmacology, efficacy, safety, and tolerability data from phase II and III trials in children and adolescents (6-17 years old). Viloxazine clinical efficacy has also been further demonstrated by post hoc analyses of pediatric clinical trial results. EXPERT OPINION: Current stimulant and nonstimulant treatments for ADHD may be suboptimal given low response rates and that tolerability issues are frequently experienced. Preclinical and clinical evidence has implicated both the role of catecholamine and serotonin signaling in the pathophysiology of ADHD and the pharmacologic effect of viloxazine on these critical neurotransmitter systems. With a relatively rapid onset of action, sustained symptom improvement, and clinical benefit in ADHD-associated impairments (functional and social), viloxazine ER represents a novel and emerging ADHD treatment option.

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.

Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

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.

Modafinil, an atypical CNS stimulant?

Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.

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.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.