Assessment and Treatment of Attention-Deficit/Hyperactivity Disorder in Children

Educational Objectives

The goal of this program is to improve diagnosis and management of attention-deficit/hyperactivity disorder (ADHD). After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate potency among various stimulants used in treatment of ADHD.
2. Cite evidence for use of stimulants in ADHD in patients with comorbid anxiety.
3. List the benefits of α-agonists used to manage symptoms of ADHD.

Summary

Attention-deficit/hyperactivity disorder (ADHD): primary care clinicians can assess and treat ADHD because of their longitudinal relationships with patients and families and their understanding of the development of children and other family members; the American Association of Pediatrics encourages ADHD evaluation and treatment in general pediatric settings; Faraone et al (2024) differentiated treatment for symptomatic relief of ADHD from other symptoms or functional impairments associated with ADHD and found robust effects of medications on ADHD and of behavioral interventions for ADHD and other related symptoms

Core components of ADHD treatment: include medications (stimulants, nonstimulants) and psychosocial treatments; psychosocial treatment involves providing awareness about ADHD, its manifestations, and its interference in functioning; it is usually the first step; clinicians use psychosocial treatment for some time before switching to medications or behavioral treatment; psychosocial treatment includes parent management training (PMT), core components of which comprise positive reinforcement for desired behaviors, providing structure, identifying reasons for less desired behaviors and their consequences, and ensuring that consequences do not reinforce those behaviors; PMT can have an additive effect with medication and is especially helpful for improving functional outcomes; it is first-line therapy in most cases in young children; PMT in older children focuses on the parent; skills training may directly help older children

Medications: stimulants are the first-line treatment for ADHD because of their rapid onset of action, long-term safety and efficacy, and large effect size; methylphenidate inhibits the reuptake of dopamine and norepinephrine; the amphetamine class directly releases dopamine along with reuptake inhibition; amphetamines are generally 2 times more potent than methylphenidate but also have relatively higher adverse effects

Switching medications: may be required because of unavailability; benefits of switching include avoiding difficulties because of shortages and preventing side effects from some formulations

Considerations when prescribing stimulants: include the duration of patient symptoms and academic demands during the day; long-acting formulations often contain a different proportion of immediate and delayed-release medications, which is a factor if symptoms are worse in the afternoon vs the morning; sleep disruption is a common ADHD manifestation; consider short-acting over long-acting in such cases to avoid interference with sleep initiation; determine whether the patient needs a period in the middle of the day without stimulants that suppress appetite; determine whether patients can take medications >1 time per day; determine whether patients have significant rebound symptoms or irritability after the effect of the stimulant wears off; consider medications without steep drops in levels in such cases

Methylphenidate formulations: among short-acting preparations, dexmethylphenidate (Focalin, Focalin XR) is twice as potent as methylphenidate; long-acting formulations have different proportions of immediate and delayed release components; methylphenidate (eg, Concerta, Daytrana, Ritalin) has the most gradual increase and decrease in medication levels and may be considered in patients sensitive to rapid changes in drug levels; the mixed amphetamine salts extended-release formulation (Adderall XR) has an ≈8-hr duration, while lisdexamfetamine (Vyvanse) has a significantly longer duration; the website https://www.adhdmedicationguide.com/ has detailed information about medications for ADHD and considerations thereof; leverage differences in various drugs and formulations for patients’ benefit; lisdexamfetamine has a gradual increase and decrease in serum levels; consider potency when switching from one drug class to another; the metabolism is more variable in younger children; methylphenidate transdermal patch (Daytrana) usually requires relatively lower doses considering its administration and metabolism

Stimulant side effects and medical considerations: cardiac — stimulants increase heart rate by 1 to 2 bpm on average and increase systolic and diastolic blood pressure, which is usually not clinically significant, but borderline patients should be monitored; tachyarrhythmia is a theoretical concern; electrocardiography is rarely indicated before initiating stimulants; psychiatric — stimulants are contraindicated in patients with untreated mania or psychosis but not in well-controlled patients; there is mixed evidence for stimulants in patients with comorbid anxiety; anxiety can worsen with stimulants in patients with significant physical symptoms or who are sensitive to physical symptoms; in other patients, anxiety can improve with stimulants; treating ADHD also reduces anxiety; tics — there is no consistent evidence to support stimulants as a cause; consider the risk for anorexia as stimulants may cause appetite suppression; endocrine — patients may have growth deceleration with consistent and prolonged use of stimulants, most evident after 3 to 5 yr of use; monitor children, especially those with short stature or a family history of short stature; stimulants can also exacerbate untreated hyperthyroid symptoms

Nonstimulants: reasons for consideration include patient and family preference, significant comorbidities, avoiding drug abuse potential, and ensuring controlled medication administration; α-agonists may be particularly helpful in patients with a history of hyperarousal, trauma, or aggression; nonstimulants can be combined with stimulants to reduce stimulant side effects; nonstimulants include norepinephrine reuptake inhibitors (NERIs; atomoxetine, viloxazine) and α-agonists (guanfacine, clonidine)

General principles with use of α-agonists: monotherapy with α-agonists significantly reduces ADHD symptoms, including hyperactivity, impulsivity, and inattention; α2-agonists may be combined with stimulants; benefits of α-agonists include the absence of appetite suppression, sedation-sleep induction, and potential treatment of tics; combined α-agonists and stimulants are effective, especially in the evening hours; the US Food and Drug Administration (FDA) approved the combination of α-agonists and stimulants; disadvantages include somnolence (more severe for clonidine than guanfacine) and effects on blood pressure; clonidine should be taken consistently to avoid rebound hypertension; taper the dose rather than abruptly discontinuing; α-agonists are not as effective as stimulants in managing inattention

General principles of using NERIs: NERIs are less effective than stimulants for inattention and hyperactive, impulsive symptoms; symptom coverage is a full day with once-daily dosing; atomoxetine takes several weeks to show effect; viloxazine may have a faster onset than atomoxetine; dosing of atomoxetine is weight-based; the most common side effects are gastrointestinal upset, fatigue, and appetite suppression; atomoxetine is associated with rare hepatotoxicity; atomoxetine and viloxazine have black box warnings for suicidal ideation; fewer side effects for viloxazine are documented; NERIs are significantly effective in patients with comorbid anxiety

Psychiatric comorbidities: comorbidity with ADHD is the rule, not the exception; patients are at risk for anxiety, mood disorders, post-traumatic stress disorder, substance use disorder (SUD), learning disorders, sleep disorders, and disruptive behavior disorders

Key action statement for comorbidity and ADHD: screen patients with ADHD for comorbid, developmental, and physical conditions; consider combined treatment, including medications and behavioral therapy, particularly for comorbid anxiety disorders and disruptive behavior; identify the most impairing condition and evaluate the effect of one condition on the other and the effect of the treatment of one condition on the other

ADHD and SUD: ADHD is a significant risk factor (2-3 times) for SUD; it is underidentified in patients already undergoing SUD treatment; ADHD is also associated with more severe substance use; stimulant treatment reduces the subsequent risk of developing SUD

ADHD treatment and age: for preschool children <6 yr of age, treatment is initiated with behavioral intervention, often parent-focused intervention; PMT has the most evidence; classroom interventions are also helpful; PMT is effective for various conditions besides ADHD; medications are recommended for significant functional impairment or when the risk of not treating outweighs treatment risk, including safety concerns and functional difficulties in the classroom; access to behavioral interventions can be challenging; consider medication as the initial treatment if patients are unable to access treatment and delayed treatment has associated risk; Preschool ADHD Treatment Study (Greenhill [2006]) established methylphenidate as an effective and relatively safe treatment in preschool-aged children; effect size was small; adverse effects included irritability; symptoms persist in ≤50% of preschool children growing into adolescence; symptoms may shift; hyperactivity is predominant in childhood, while restlessness or inattention are predominant in adolescence and adulthood; 5 out of 9 symptoms are required for diagnosing inattention in patients ≥17 yr of age; adolescents can have particular challenges as the need for organizational and executive function increases; opportunities for risky behavior increase in adolescence; consider the risk for stimulant misuse

Readings

FaraoneSV, Bellgrove MA, Brikell I, et al. Attention-deficit/hyperactivity disorder [published correction appears in Nat Rev Dis Primers. 2024;10(1):29. doi: 10.1038/s41572-024-00518-w]. Nat Rev Dis Primers. 2024;10(1):11. doi:10.1038/s41572-024-00495-0; Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD [published correction appears in J Am Acad Child Adolesc Psychiatry. 2007;46(1):141]. J Am Acad Child Adolesc Psychiatry. 2006;45(11):1284-1293. doi:10.1097/01.chi.0000235077.32661.61; Linden S, Bussing R, Kubilis P, et al. Risk of suicidal events with atomoxetine compared to stimulant treatment: a cohort study. Pediatrics. 2016;137(5):e20153199. doi:10.1542/peds.2015-3199; McCabe SE, Dickinson K, West BT, et al. Age of onset, duration, and type of medication therapy for attention-deficit/hyperactivity disorder and substance use during adolescence: a multi-cohort national study. J Am Acad Child Adolesc Psychiatry. 2016;55(6):479-486. doi:10.1016/j.jaac.2016.03.011; Neuchat EE, BockludBE, Kingsley K, et al. The role of alpha-2 agonists for attention deficit hyperactivity disorder in children: a review. Neurol Int. 2023;15(2):697-707.doi:10.3390/neurolint15020043; Russell V, de Villiers A, Sagvolden T, et al. Differences between electrically-, ritalin- and D-amphetamine-stimulated release of [3H]dopamine from brain slices suggest impaired vesicular storage of dopamine in an animal model of attention-deficit hyperactivity disorder. Behav Brain Res. 1998;94(1):163-171. doi:10.1016/s0166-4328(97)00177-0; Stevens JR, Wilens TE, Stern TA. Using stimulants for attention-deficit/hyperactivity disorder: clinical approaches and challenges. Prim Care Companion CNS Disord. 2013;15(2):PCC.12f01472. doi:10.4088/PCC.12f01472; Wigal SB. Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults. CNS Drugs. 2009;23(Suppl 1):21-31. doi:10.2165/00023210-200923000-00004.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Platt was recorded at the 50th Annual Pediatric Trends, held virtually May 14-17, 2024, and presented by the Johns Hopkins University School of Medicine, Baltimore, MD, and Johns Hopkins Children's Center, Baltimore. For information on future CME activities from this presenter, please visit https://hopkinscme.cloud-cme.com. Audio Digest thanks the speakers and the presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

PD704701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.