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Interventions, conclusions, acknowledgments, improving care management in attention-deficit/hyperactivity disorder: an rct.

POTENTIAL CONFLICT OF INTEREST: Drs Fiks and Grundmeier are the inventors of the Care Assistant, which was used as the patient portal for patients with attention-deficit/hyperactivity disorder in this study; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

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James P. Guevara , Thomas J. Power , Katherine Bevans , Lisa Snitzer , Siobhan Leavy , Denise Stewart , Caroline Broomfield , Salima Shah , Robert Grundmeier , Jeremy J. Michel , Steven Berkowitz , Nathan J. Blum , Matthew Bryan , Heather Griffis , Alexander G. Fiks; Improving Care Management in Attention-Deficit/Hyperactivity Disorder: An RCT. Pediatrics August 2021; 148 (2): e2020031518. 10.1542/peds.2020-031518

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Video Abstract

To compare the effectiveness of care management combined with a patient portal versus a portal alone for communication among children with attention-deficit/hyperactivity disorder (ADHD).

Randomized controlled trial conducted at 11 primary care practices. Children aged 5 to 12 years old with ADHD were randomly assigned to care management + portal or portal alone. The portal included parent-reported treatment preferences and goals, medication side effects, and parent- and teacher-reported ADHD symptom scales. Care managers provided education to families; communicated quarterly with parents, teachers, and clinicians; and coordinated care. The main outcome, changes in the Vanderbilt Parent Rating Scale (VPRS) score as a measure of ADHD symptoms, was assessed using intention-to-treat analysis.

A total of 303 eligible children (69% male; 46% Black) were randomly assigned, and 273 (90%) completed the study. During the 9-month study, parents in the care management + portal arm communicated inconsistently with care managers (mean 2.2; range 0–6) but similarly used the portal (mean 2.3 vs 2.2) as parents in the portal alone arm. In multivariate models, VPRS scores decreased over time (Adjusted β = −.015; 95% confidence interval −0.023 to −0.07) in both groups, but there were no intervention-by-time effects (Adjusted β = .000; 95% confidence interval −0.011 to 0.012) between groups. Children who received ≥2 care management sessions had greater reductions in VPRS scores than those with fewer sessions.

Results did not provide evidence that care management combined with a patient portal was different from portal use alone among children with ADHD. Both groups demonstrated similar reductions in ADHD symptoms. Those families with greater care management engagement demonstrated greater reductions than those with less engagement.

Electronic patient portals and care managers have been used to facilitate communication among clinicians and families of children with mental health disorders. The relative effectiveness of patient portals vis-à-vis care managers on outcomes in attention-deficit/hyperactivity disorder is not known.

In this randomized comparative effectiveness trial that included 303 children with attention-deficit/hyperactivity disorder, there were no significant intervention-by-time differences in parent-reported outcomes between groups. Care management did not enhance communication and improve outcomes beyond a patient portal alone.

Attention-deficit/hyperactivity disorder (ADHD), characterized by inattention, impulsivity, and hyperactivity, is the most common chronic neurobehavioral disorder in children. 1 , 2   Prevalence among children in the United States has risen to 12%. 3   Effectiveness of treatment of ADHD, supported by clinical trials, consists of psychotropic medications, such as methylphenidate, and behavior therapy, alone or in combination. 2 , 4   Unfortunately, adherence to ADHD treatment is poor, limiting treatment effectiveness. 5 , 6  

Shared decision-making (SDM) may be helpful for conditions like ADHD that have evidence-based options and variation in how families weigh options. 7   SDM is a process in which families and clinicians jointly engage in decision-making, exchange information and treatment preferences, and work to decide on a treatment plan. 8   Because children with ADHD use services across multiple systems, poor communication between families and health and education systems can limit SDM and lead to poor adherence to treatment. 9  

Two strategies have been proposed to enhance communication and promote greater SDM in ADHD. One is the use of electronic patient portals, online health care applications that allow patients to interact and communicate with providers and manage their health. 10 – 12   Portals designed for ADHD have been found to increase exchange of information between clinicians, parents, and teachers. 13   Another is the use of care managers, who function to promote patient engagement and coordinate care across care systems. In studies of adolescents and adults with depression, care managers have demonstrated favorable findings regarding depressive symptoms and functioning. 14 – 16   Data are limited regarding the use of care managers with ADHD. 17   Given the growing access to patient portals with ADHD-specific components, we sought to determine the comparative effectiveness of patient portals combined with care managers versus patient portals alone on ADHD symptoms, goal attainment, and patient-reported outcome (PRO) measures. We postulated that the combination of patient portals and care managers would be associated with greater reductions in ADHD symptoms over time than portal use alone and that effects would vary by race and/or ethnicity and income.

We conducted a prospective randomized comparative effectiveness trial involving 11 primary care pediatric practices affiliated with a large children’s hospital from March 10, 2016, to April 12, 2019. The practices included 5 urban practices and 6 suburban practices that used a common electronic health record (EHR) and an ADHD-specific patient portal known as the ADHD Care Assistant. 18 , 19   Five of the practices had colocated behavioral health services. We recruited the practices using letters of invitation and in-person presentations. The study was approved by the Institutional Review Board at the Children’s Hospital of Philadelphia and was registered at Clinicaltrials.gov (NCT02716324) before recruitment of participants.

Children were eligible for the study if they received care at a participating practice, had an ADHD diagnosis code ( International Classification of Diseases, Ninth Revision [ICD-9] code 314) recorded at an ambulatory visit in the past year, and were aged 5 through 12 years old. Children were excluded if they had a diagnosis of autism spectrum disorder (ICD-9 code 299), conduct disorder (ICD-9 code 312), psychosis (ICD-9 code 298), bipolar disorder (ICD-9 code 296) or suicidal ideation or intent (ICD-9 codes E950.0–E958.9) in the past 12 months. Lists of potentially eligible children were identified from EHR records and were verified by primary care clinicians at the practices. A random sample of at least 300 eligible children stratified by practice, sex, and age group (5–7 vs 8–12 years old) were selected to achieve a representative sample. Parents of selected children were mailed a recruitment letter and a stamped self-addressed postcard to opt out. Families who did not opt out within 2 weeks were called to screen for eligibility, provide study information, and schedule an enrollment visit. We randomly selected additional children from the same strata as those who declined participation, were ineligible, or were unable to be contacted. Children were consented and randomly assigned 1:1 within strata to the 2 groups by the study biostatistician using a random number generator.

We sought to compare the effectiveness of an ADHD portal embedded in the EHR (portal alone) with the portal combined with an ADHD care manager (care management + portal). The ADHD portal, known as the ADHD Care Assistant, was designed to (1) collect and share patient and family treatment preferences and goals with a clinician; (2) trend ADHD symptoms, performance impairment ratings, medication side effects, treatment receipt, and medication side effects by using electronically submitted parent and teacher reports; (3) provide a repository of ADHD educational materials; and (4) support information sharing between parents and teachers ( Fig 1 ). The ADHD Care Assistant enabled clinicians to send survey-driven ADHD symptom rating scales to a child’s parent and teacher via e-mail. Data collected through this system were displayed directly to the clinician within the EHR. Parents were provided an opportunity to view teacher reports, and teachers could view parent-submitted reports with parental consent. 20   The frequency of e-mails from the portal varied from biweekly to every 3 months at the discretion of the clinician in consultation with the family. Parent and teacher usage of the ADHD Care Assistant during study participation was extracted from the EHR.

Design for the ADHD Care Assistant portal. The figure shows the design for the ADHD SDM portal. The portal is able to (1) capture and share patient and family treatment preferences and goals; (2) monitor symptoms, treatment receipt, and side effects as well as goal attainment; and (3) facilitate communication between parent, teachers, and primary care clinicians. Data on behavior therapy and school-based intervention receipt are not available in the ADHD Care Assistant.

ADHD care managers were bachelor’s-trained individuals who were responsible for communicating information and facilitating coordination of care. The care managers confirmed family treatment preferences and goals, provided education on the treatment of ADHD and associated conditions, monitored attainment of parent-directed goals and emerging issues, and provided resources and assistance with concerns for patients with ADHD and families. The care managers sought to contact families, teachers, and clinicians by phone, text message, or e-mail every 3 months or sooner if problems arose. The care managers completed a fidelity checklist after each encounter to assess self-reported task completion (0, not completed; 1, partially completed; 2, fully completed) and summarized the sessions as a telephone encounter in the EHR.

We collected demographic information (child age, child sex, child race and/or ethnicity, child Supplemental Security Income [SSI] status, parental education level, urban or suburban residence, free or reduced lunch status, and school type [public, charter, or private]) at baseline. In addition, we geocoded participant home addresses and used American Community Survey tract-level data to obtain median family neighborhood income levels. ADHD medication (stimulants, α-agonists, and atomoxetine) fills and dates for each child during the study period were determined by abstraction from the EHR.

Change in ADHD symptoms was the primary outcome. We used the ADHD symptom subscale of the Vanderbilt Parent Rating Scale (VPRS) to assess ADHD symptoms. 21   The VPRS has been shown to have excellent internal consistency (α = .90–.94) and concurrent validity ( r = 0.79) in relation to diagnostic interviews. The VPRS includes 18 items that correspond to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition symptom criteria and has a 4-point Likert response category (never [0] to very often [3]) for each item. We summed items on the VPRS to obtain an overall symptom score ranging from 0 to 54, with lower scores indicating fewer ADHD symptoms.

Changes in goal attainment and PROs were secondary outcomes. We identified family treatment goals through use of the ADHD Preference and Goals Instrument, a parent-reported 46-item tool that queries parents on their treatment preferences (medications and/or behavioral therapy) and goals for treatment. 22   A primary goal for each family was identified and categorized as academic, behavioral, or relational by consensus of the study team. Goal attainment scaling (GAS) was used to allow parents to rate the degree to which their goal was met over time and was scaled from 0 (no change) to 6 (goal completely met). 23 – 25   PRO measures were completed by a parent proxy and by children aged ≥8 for school performance, student engagement, peer relationships, family belonging, and teacher connectedness. These PRO measures consisted of Patient-Reported Outcomes Measurement Information System short forms and Healthy Pathway scales, which are brief, reliable, and precise measures of patient-reported health status. 26 – 29   Higher GAS and PRO scores indicate better outcomes.

Outcome measures were collected at baseline and at 3-month intervals for 9 to 12 months after enrollment by using Research Electronic Data Capture e-mail surveys. Research staff, who were blinded to participants’ study arms, contacted nonresponders at each study visit by phone to complete the surveys. In addition, we obtained VPRS scores from the ADHD portal, if available within 30 days of the corresponding Research Electronic Data Capture survey, for nonresponders.

We employed imputation methods for missing items for 2 of the outcomes (VPRS and PRO measures). If a participant had 1 or 2 items missing within 1 of the 2 domains on the VPRS or any of the PRO measures, the average of the nonmissing items for the domain or PRO measure was assigned to obtain a score. No between–study arm differences between pre- and postimputation VPRS and PRO mean scores were observed for cases and controls. VPRS subdomains and PRO measures with >2 missing items were not imputed. We elected not to impute missing GAS scores.

To determine differences in outcomes between groups, we followed the standard of an intention-to-treat repeated-measures longitudinal analysis. To check on the adequacy of randomization, patient characteristics were compared between groups. To assess bivariate associations between study arm and outcome at each of the study visits, t tests were used for ADHD symptoms, parent and child PRO measures, and goal attainment. To assess differences in outcomes, we used linear mixed-effects models to account for missing outcome values under a missing-at-random assumption. We examined results from analogous generalized estimating equations models to examine the robustness of our conclusions to model selection. 30 , 31   Intervention-by-time interactions for each outcome were used to represent the adjusted difference in outcome measures between the 2 groups over time. Models were adjusted for seasonality (fall, winter, spring, and summer), child age (5–7 and 8–12 years), child sex, child race and/or ethnicity (white, Black, Hispanic, or other), free or reduced school lunch, metropolitan status (urban or suburban), child SSI status, parent education level (up to high school, some college, or college degree), school type (public, private, or charter), median neighborhood income, and ADHD medication status. To account for clustering, clinic site was included in each model as a random effect. With a sample of 300, we had power of 0.87 to detect a difference of 2.5 points on the VPRS scores between groups, assuming α = .05, 80% follow-up, and moderate correlation ( r = 0.6) over 9 months. The difference of 2.5 points represented a small clinically meaningful effect size from our pilot study. We conducted a sensitivity analyses to examine the impact of intervention dosage (ie, number of care management sessions) on ADHD symptoms. All analyses were conducted by using Stata 15 statistical software (Stata Corp, College Station, TX).

We identified 3118 potential participants aged 5 to 12 years old with ADHD from the 11 practices ( Fig 2 ). Of these, we randomly selected and stratified 960 children. We sent 875 recruitment letters, but 572 were not enrolled for the following reasons: 112 declined participation, 174 were ineligible, and 286 were unable to be reached. Thus, we enrolled and randomly assigned 303 eligible children: 154 to care management + portal and 149 to portal alone. Of these, 273 (90.1%) completed the study, as defined by completing the final VPRS: 143 (93%) in care management + portal and 130 (87%) in portal alone.

Participant flow through the study.

After randomization, children in both study arms had similar sociodemographic characteristics ( Table 1 ). The average age was 8.5 years old, with most (91%) ≥8 years of age. Two-thirds were male. Children were racially and socioeconomically diverse, with 51% residing in urban locations. More than half qualified for free or reduced school lunch (54%), and more than half attended public schools (60%). As expected, a slight majority (53%) of children reported receiving an ADHD medication at baseline.

Demographic Characteristics of Study Participants at Baseline

Participants were children aged 5–12 y old with ADHD who were recruited from 11 primary care pediatric practices. Numbers may not add to column totals because of missing data.

Over the course of the study period, 206 (68%) study participants used the ADHD portal to complete a parent-reported VPRS ( Table 2 ). The average number of VPRSs completed was similar in both arms: 2.3 in care management + portal and 2.2 in portal alone. Nearly one-third of participants (30%) had a teacher use the patient portal to complete a Vanderbilt Teacher Rating Scale. In care management + portal, most parents (96%) had at least 1 care management session. One-third of children (34%) had a teacher engage with the care managers. When care manager fidelity checklists were examined, 66% of parent and 63% of teacher sessions were rated as fully completed on all relevant items (data not shown) and the rest as partially completed or not relevant.

Portal and Care Manager Sessions Completed, by Study Arm

Participants were children aged 5–12 y old with ADHD who were recruited from 11 primary care pediatric practices. Numbers may not add to column totals because of missing data. Families of all participants were contacted at least every 3 mo to complete an online ADHD portal survey of ADHD symptoms. Only families of participants in the care manager + portal group were contacted at least every 3 mo to participate in a care management session. n/a, not applicable.

Completion of a survey through the ADHD portal by either a parent or a teacher constituted a portal session.

Table 3 shows the primary outcome, mean VPRS scores, by study visit and group. All 303 participants completed study visit 1, 258 (85%) completed study visit 2, 236 (78%) completed study visit 3, and 273 (90%) completed study visit 4. Mean VPRS scores decreased over time, indicating clinical improvement in ADHD symptoms, but there were no statistically significant differences in mean scores between groups at any study visit. GAS, parent proxy–reported PRO, and child-reported PRO scores did not change over time and did not differ between groups at any study visit (Supplemental Tables 5 through 7).

VPRS Scores by Study Visit Between Groups

Participants were children aged 5–12 y old with ADHD who were recruited from 11 primary care pediatric practices. Differences in mean VPRS scores at study visits were assessed by using the t test.

To assess changes between groups in VPRS scores, results from the previously described model are presented in Table 4 . The intervention-by-time interaction in the full model was not significant (β = .00; 95% confidence interval [CI] −.01 to .01), indicating no difference between groups in changes in VPRS scores over time. In models without the interaction term, time (days) was significant, suggesting that VPRS scores decreased an average of 0.015 points per day or roughly 4 points over the course of the 9-month intervention period for both groups, a clinically meaningful improvement. Urban and medication status were also both significant, indicating that children residing in urban compared with suburban residences had VPRS scores that were greater and children on ADHD medications, as opposed to no medications, had VPRS scores that were lower. There were no adverse effects from either intervention identified, and interactions of intervention by race or income were not significant, suggesting no heterogeneity of treatment effects. Results from the generalized estimating equations model were consistent with results from the linear mixed-effects model.

Adjusted VPRS Scores

Participants were children aged 5–12 y old with ADHD who were recruited from 11 primary care pediatric practices. After imputation, there were 1034 individual person–time points. Linear mixed-effects models regressed VPRS scores on intervention status, time (days), intervention by time, race, urbanicity, education, medication status, median household income, and season and a random effect for clinic site.

Medication status reported by parent at time of survey; if medication status was missing on the self-reported survey, the status was included from the EHR at a clinic visit within 1 mo of the corresponding survey date.

We conducted a sensitivity analysis to determine if there was a dose-response in which greater engagement among care management + portal participants resulted in greater declines in VPRS scores. After adjustment for seasonality, we found that those participants who received ≥2 care management sessions experienced statistically significantly greater decreases in VPRS scores (−4.7; 95% CI −8.0 to −1.4) than those with 1 or 0 sessions. There were no demographic differences by the number of care management sessions attended. This nonrandomized result suggests that greater engagement of participants within the care management intervention resulted in greater symptom improvement.

In this comparative effectiveness study of 2 communication strategies, an electronic patient portal combined with a care manager versus a portal alone, we found no difference over time in primary or secondary outcomes between the 2 groups. We observed an overall improvement in ADHD symptoms over time in both groups but little to no change in goal attainment or PROs at any time point. This suggests that care management did not improve ADHD symptoms over and above that of the patient portal alone.

Our finding that children in both groups showed improvement in ADHD symptoms over time is consistent with previous studies employing patient portals for ADHD. Epstein et al 13   found that community pediatricians using an ADHD portal were significantly more likely to collect information from parents and teachers than those using usual care. Nagykaldi et al 32   found that the use of a portal focused on preventive care resulted in increased patient activation and greater patient-centered care, and users were more likely to receive needed preventive care.

There was variable engagement by parents with the care manager. It is not entirely clear why parents did not consistently engage to a greater extent with the care manager than with the portal as we had postulated. Our results revealed modest engagement by parents and teachers with care managers. Care managers were instructed to engage with parents and teachers virtually at least every 3 months; however, care managers found it challenging to contact parents and teachers to schedule sessions. In some instances, care managers were unable to identify contact information for teachers despite calls to schools. Given the virtual nature of the care management intervention in this study, face-to-face contact was lacking and may have contributed to the inconsistent engagement. In a study of community health workers, those workers who provided face-to-face communication saw more beneficial effects on the quality of care and a reduction in hospital days. 33   In addition, systematic reviews of collaborative care trials among adults with depression have consistently demonstrated that care management involving face-to-face contact is associated with modest but sustained improvement in depression outcomes (standardized mean difference 0.25; 95% CI 0.18 to 0.32) compared with usual care. 34 , 35   Our preplanned sensitivity analysis revealed that those with a greater number of care management sessions had greater reductions in ADHD symptoms than those with fewer sessions, suggesting the importance of family engagement for this intervention to be effective.

There were several limitations to our study findings. First, our study was conducted in a single geographic area within an integrated pediatric health care system. Results may not be generalizable to other geographic areas or other health care systems. Second, our care managers primarily employed electronic means of communication, which may have limited engagement, as discussed above. Third, we did not enroll teachers in our study because of challenges in connecting with and obtaining formal approval from schools. This limitation did not permit us to interview teachers to discern their perceptions of the interventions. Finally, we lacked a no intervention control group, because use of the electronic portal was considered standard of care at our institution during the study period. This limited our ability to formally test benefits of the portal over no portal care.

In this comparative effectiveness study, we found no evidence that care management combined with a patient portal produced patient outcomes different from those of a patient portal alone among school-aged children with ADHD. Both groups demonstrated similar reductions in ADHD symptoms over time. Overall, there was variable engagement by parents with care managers, which likely limited its impact. Those families with greater care management engagement, as demonstrated by the number of sessions attended, showed greater reductions in ADHD symptoms over time than those with less. There was no heterogeneity of treatment effects as a function of race and/or ethnicity or household income. In future studies, researchers investigating the effects of care management should consider methods (eg, face-to-face meetings) to better engage families and teachers.

We thank the Pediatric Research Consortium (PeRC) at the Children’s Hospital of Philadelphia and all participating practices and clinicians for their support of this study. We also thank Stephanie Liu, MS, for her assistance with data collection.

Dr Guevara conceptualized and designed the study, oversaw the data collection and analysis, drafted the initial manuscript, and revised the manuscript; Drs Power and Bevans, Ms Snitzer, Dr Leavy, Ms Stewart, and Drs Grundmeier, Berkowitz, Blum, Bryan, and Fiks helped conceptualize and design the study, interpreted the data analysis, and critically reviewed the manuscript for intellectual content; Ms Broomfield and Ms Shah conducted the data collection, assisted with the data analysis, and critically reviewed the manuscript for intellectual content; Drs Michel and Griffis conducted the data analysis and critically reviewed the manuscript for intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Drs Guevara and Griffis had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

This work was presented in part at the annual meeting of the Pediatric Academic Societies; April 27–30, 2019; Baltimore, MD; and at the International Forum on Quality and Safety in Healthcare; September 18–20, 2019; Taipei, Taiwan.

A complete, cleaned, and deidentified data set (including a data dictionary) will be made available to other investigators after all analyses have been conducted and after publication of this article. To obtain this data set, investigators may contact the study principal investigator, who will provide a data sharing agreement. The data sharing agreement will permit the data set to be shared once an institutional review board protocol has been approved at the investigators’ home institution and the investigators have signed a pledge to not attempt to identify individual study subjects. The data set will be made available on a CD-ROM or through a secure FTP site.

This trial has been registered at www.clinicaltrials.gov (identifier NCT02716324).

Dr Berkowitz’s current affiliation is Department of Psychiatry, University of Colorado, Denver, Colorado.

FUNDING: Funding was provided by the Patient Centered Outcomes Research Institute (PCORI), award (CDR-1408-20669). The statements in this article are solely the responsibility of the authors and do not necessarily reflect the views of the Patient-Centered Outcomes Research Institute, its Board of Governors, or its Methodology Committee.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2021-050766 .

attention-deficit/hyperactivity disorder

confidence interval

electronic health record

goal attainment scaling

International Classification of Diseases, Ninth Revision

patient-reported outcome

shared decision-making

Supplemental Security Income

Vanderbilt Parent Rating Scale

Competing Interests

Supplementary data.

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Attention Deficit Hyperactivity Disorder (ADHD): A Case Study and Exploration of Causes and Interventions

• First Online: 02 March 2019

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• Bijal Chheda-Varma 5  

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The male to female ratio of ADHD is 4:1. This chapter on ADHD provides a wide perspective on understanding, diagnosis and treatment for ADHD. It relies on a neurodevelopmental perspective of ADHD. Signs and symptoms of ADHD are described through the DSM-V criteria. A case example (K, a patient of mine) is illustrated throughout the chapter to provide context and illustrations, and demonstrates the relative merits of “doing” (i.e. behavioural interventions) compared to cognitive insight, or medication alone. Finally, a discussion of the Cognitive Behavioral Modification Model (CBM) for the treatment of ADHD provides a snapshot of interventions used by clinicians providing psychological help.

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Safren, S. A., Otto, M. W., Sprich, S., Winett, C. L., Wilens, T. E., & Biederman, J. (2005, July). Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms. Behaviour Research and Therapy, 43 (7), 831–842. ISSN 0005-7967. http://dx.doi.org/10.1016/j.brat.2004.07.001 . http://www.sciencedirect.com/science/article/pii/S0005796704001366 .

Sibley, M. H., Kuriyan, A. B., Evans, S. W., Waxmonsky, J. G., & Smith, B. H. (2014). Pharmacological and psychosocial treatments for adolescents with ADHD: An updated systematic review of the literature. Clinical Psychology Review, 34 (3), 218–232. https://doi.org/10.1016/j.cpr.2014.02.001 .

Simchon, Y., Weizman, A., & Rehavi, M. (2010). The effect of chronic methylphenidate administration on presynaptic dopaminergic parameters in a rat model for ADHD. European Neuropsychopharmacology, 20 (10), 714–720. ISSN 0924-977X. https://doi.org/10.1016/j.euroneuro.2010.04.007 . http://www.sciencedirect.com/science/article/pii/S0924977X10000891 .

Swanson, J. M., & Castellanos, F. X. (2002). Biological bases of ADHD: Neuroanatomy, genetics, and pathophysiology. In P. S. Jensen & J. R. Cooper (Eds.), Attention deficit hyperactivity disorder: State if the science, best practices (pp. 7-1–7-20). Kingston, NJ: Civic Research Institute.

Toplak, M. E., Connors, L., Shuster, J., Knezevic, B., & Parks, S. (2008, June). Review of cognitive, cognitive-behavioral, and neural-based interventions for attention-deficit/hyperactivity disorder (ADHD). Clinical Psychology Review, 28 (5), 801–823. ISSN 0272-7358. http://dx.doi.org/10.1016/j.cpr.2007.10.008 . http://www.sciencedirect.com/science/article/pii/S0272735807001870 .

Wu, J., Xiao, H., Sun, H., Zou, L., & Zhu, L.-Q. (2012). Role of dopamine receptors in ADHD: A systematic meta-analysis. Molecular Neurobiology, 45 , 605–620. https://doi.org/10.1007/s12035-012-8278-5 .

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Chheda-Varma, B. (2019). Attention Deficit Hyperactivity Disorder (ADHD): A Case Study and Exploration of Causes and Interventions. In: Barry, J.A., Kingerlee, R., Seager, M., Sullivan, L. (eds) The Palgrave Handbook of Male Psychology and Mental Health. Palgrave Macmillan, Cham. https://doi.org/10.1007/978-3-030-04384-1_15

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Patient Case Study

Case: johnny (8-year old male), diagnosis: adhd.

Johnny was an eight year-old boy with a diagnosis of ADHD when he and his mother came to our practice seeking help for his symptoms. For years, Johnny had struggled with aggressive, impulsive and oppositional tendencies. While he was highly intelligent, his school performance suffered due to struggles with emotional management.

As an infant, Johnny was colicky and was prescribed multiple rounds of antibiotics due to recurrent ear infections, ultimately needing tubes to help drain the middle ear. He also struggled with encopresis.

Upon a physical exam, it was noted that Johnny had an obvious and inflamed “lip-licking ring” around his mouth along with nasal congestion. A comprehensive battery of testing only found a few abnormalities. Johnny was heterozygous for a single nucleotide polymorphism of the methylenetetrahydrofolate reductase (MTHFR) enzyme at position 677 with a single C to T substitution. Trace metal hair and organic acid testing were all within normal limits. Based on the symptoms and a history of ear infections, dairy was removed from the diet. Lithium orotate, at one mg twice daily, was prescribed to help reduce his aggressive, impulsive and oppositional tendencies.

Upon follow-up, Johnny’s demeanor had dramatically improved. He was cooperative and emotionally engaging. The lip-licking ring had resolved. Both Johnny’s mother and Johnny were excited about the improvements and ready to continue integrative treatment.

Case Summary

Chronic ear infections are often a symptom of food allergies. While the research is not exhaustive, studies have found consistent correlations between cow’s milk allergy and middle ear infections in children ( Bhombal 2006 , Juntti 1999 ). Removing dairy products often results in a reduction or elimination of ear infections.

And while lithium is a well-known treatment for bipolar, it also has well-documented anti-aggressive effects ( Müller-Oerlinghausen 2010 ). In children struggling with oppositional and aggressive tendencies, low-dose lithium can be a straightforward treatment to improve symptoms.

Want to learn nutritional and functional medicine strategies like these to help your patients? Enroll in our comprehensive Fellowship for mental health providers! Book a private phone call with Dr. James Greenblatt to learn more today.

Bhombal S, Bothwell MR, Bauer SM. Prevalence of elevated total IgE and food allergies in a consecutive series of ENT pediatric patients. Otolaryngol Head Neck Surg . 2006;134(4):578-580. doi:10.1016/j.otohns.2005.11.041

Juntti H, Tikkanen S, Kokkonen J, Alho OP, Niinimäki A. Cow’s milk allergy is associated with recurrent otitis media during childhood. Acta Otolaryngol . 1999;119(8):867-873. doi:10.1080/00016489950180199

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Childhood ADHD – Luke’s story

Posted on Thursday, 05 April 2018, in Child & Teen ADHD

In the final part of her ADHD series, Dr Sabina Dosani, Child and Adolescent Psychiatrist and Clinical Partner London, introduces Luke, a patient she was able to help with his ADHD.

ADHD is one of the most common diagnoses for children in the UK and it is thought that 1 in 10 children will display some signs. For some children, their ADHD is severe and can have a huge impact on their ability to engage in school and to build and sustain relationships. Left untreated, evidence shows that those with ADHD are more likely to get into car accidents, engage in criminal activity and may struggle to keep a job or maintain relationships.

Luke, aged six, gets into trouble a lot at school. His mother gets called by his teacher three or four times a week for incidents of fighting, kicking and running in corridors. He is unable to finish his work and becomes quickly distracted. At home, he seems unable to sit still for any length of time, has had several falls when climbing trees and needs endless prompts to tidy his toys.

At school, he annoys his classmates by his constant interruptions, however if he has one-to-one attention from a student teacher who happens to be in his class on a placement he is able to settle and finish the work set. His father was said to have been a ‘lively’ child, then a ‘bright underachiever’ who occasionally fell foul of the law.

The school thought a visit to the GP might be a good idea. At the GP surgery, Luke ran and jumped about making animal noises. He swung on the back legs of a chair and took the batteries out of an ophthalmoscope. He was referred to a me for an assessment.

After a careful assessment, which included collecting information from school, questionnaires and observations of Luke, a diagnosis of ADHD was made. Following a discussion of the treatment options, the family decided they did not want any medication.

The first-line treatment for school‑age children and young people with severe ADHD and severe impairment is drug treatment. If the family doesn’t want to try a pharmaceutical, a psychological intervention alone is offered but drug treatment has more benefits and is superior to other treatments for children with severe ADHD.

 Luke's mother was asked to list the behaviours that most concern her. She was encouraged to accept others like making noises or climbing as part of Luke’s development as long as it is safe.

Now, when Luke fights, kicks others or takes risks like running into the road he is given “time-out” which isolates him for a short time and allows him and his parents or teacher to calm down. To reduce aggression and impulsivity, Luke is taught to respond verbally rather than physically and channel energy into activities such as sports or energetic percussion playing.

Over time, Luke’s parents have become skilled at picking their battles. Home is more harmonious. They fenced their garden, fitted a childproof gate and cut some branches off a tree preventing him climbing it. His parents are concerned about Luke’s use of bad language. They have been supported to allow verbal responses as a short-term interim. Whilst these might be unacceptable in other children they are preferable to physical aggression.

At school, Luke is less aggressive, has a statement of special educational need and now works well with a classroom assistant. He has been moved to the front of the class, where the teacher can keep a close eye on him, and given one task at a time. He is given special tasks, like taking the register to the school office, so he can leave class without being expected to sit still for long periods.

Through parental training, Luke’s parents have been able to help Luke work with his challenges to better manage them. As Luke grows and develops and as he faces new challenges in life, Luke may need to revisit the efficacy of ADHD medication. His parents now feel a lot more confident in being able to help Luke and he is a happier child and more settled.

Dr Sabina Dosani Consultant Child & Adolescent Psychiatrist

Dr Sabina Dosani is a highly experienced Consultant Psychiatrist currently working for the Anna Freud Centre looking after Children and Adolescents. She has a Bachelor of Medicine and Bachelor of Surgery as well as being a member of the Royal College of Psychiatrists . Dr Dosani also has a certificate in Systemic Practice (Family Therapy).

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• News & Stories

ADHD diagnoses are rising. 1 in 9 U.S. kids have gotten one, new study finds

• Maria Godoy

About 1 in 9 children in the U.S., between the ages of 3 and 17, have been diagnosed with ADHD. That's according to a new report from the Centers for Disease Control and Prevention that calls attention-deficit/hyperactivity disorder an "expanding public health concern."

Researchers found that in 2022, 7.1 million kids and adolescents in the U.S. had received an ADHD diagnosis – a million more children than in 2016. That jump in diagnoses was not surprising, given that the data was collected during the pandemic, says Melissa Danielson, a statistician with the CDC's National Center on Birth Defects and Developmental Disabilities and the study's lead author.

She notes that other studies have found that many children experienced heightened stress, depression and anxiety during the pandemic. "A lot of those diagnoses... might have been the result of a child being assessed for a different diagnosis, something like anxiety or depression, and their clinician identifying that the child also had ADHD," Danielson says.

The increase in diagnoses also comes amid growing awareness of ADHD — and the different ways that it can manifest in children. Danielson says that may help explain why girls are becoming more commonly diagnosed with ADHD compared to boys than they had been in the past. She says boys have long been diagnosed with ADHD at around two and half times the rate of girls, but the new reports finds that difference is narrowing.

Decades ago, ADHD was thought of as a disorder of hyperactivity among boys, Danielson says. "Boys will often have hyperactive or impulsive ADHD, where they'll run into the street or jump off things or do things that might make them more likely to be injured," she says.

"Girls tend to manifest their ADHD in a more inattentive way. They'll be daydreaming or have a lack of focus or be hyper focused on a particular task that maybe is not the task that they need to be focused on," says Danielson.

The study, which appears in the Journal of Clinical Child & Adolescent Psychology, was based on data from the National Survey of Children's Health, which gathers detailed information from parents.

While the report found that the number of kids diagnosed with ADHD had risen since 2016, only about half of them were taking medication to treat the condition – compared with two-thirds of children back in 2016. The data didn't look into reasons why this might be, but Danielson notes that reports of shortages of ADHD medications began around the time the data was collected.

Dr. Max Wiznitzer, a professor of pediatric neurology at Case Western Reserve University, says he suspects some parents may be reluctant to put their kids on ADHD medication out of misguided concerns. "There's the myth that it's addictive, which it's not." He says studies have shown people treated with ADHD have no increased risk of drug abuse.

Wiznitzer says medication is important because it can help kids focus by controlling symptoms of impulsivity, overactivity and inattention. But ADHD treatment also requires therapy that can teach children — and their parents — behavioral and educational strategies to manage their condition. "It's always a two-pronged approach," he says. He finds it troubling that the report found less than half of kids and adolescents diagnosed with ADHD were getting any behavioral therapy.

The report also found that nearly 78% percent of children diagnosed with ADHD had at least one other diagnosed disorder. The most common were behavioral or conduct problems, anxiety and developmental delays. Autism and depression were also frequently observed, Danielson says.

Kids with ADHD are at increased riskfor other conditions including depression, anxiety and substance abuse and if left untreated, ADHD can raise the risk of serious health concernsin adulthood. This includes a higher risk of diabetes, heart disease and shortened life span, Wiznitzer says – which is why increased awareness and diagnosis is important.

Danielson says parents can also find information on treatment and services at CHADD — Children And Adults with ADHD, a non-profit resources organization where Wiznitzer serves on the advisory board.

He says parents seeking treatment for their kids should start with a conversation with their pediatrician.

This story was edited by Jane Greenhalgh. [Copyright 2024 NPR]

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ADHD diagnoses are rising. 1 in 9 U.S. kids have gotten one, new study finds

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopment disorders among children.

SIphotography / Getty Images

About 1 in 9 children in the U.S., between the ages of 3 and 17, have been diagnosed with ADHD. That's according to a new report from the Centers for Disease Control and Prevention that calls attention-deficit/hyperactivity disorder an "expanding public health concern."

Researchers found that in 2022, 7.1 million kids and adolescents in the U.S. had received an ADHD diagnosis – a million more children than in 2016. That jump in diagnoses was not surprising, given that the data was collected during the pandemic, says Melissa Danielson, a statistician with the CDC's National Center on Birth Defects and Developmental Disabilities and the study's lead author.

She notes that other studies have found that many children experienced heightened stress, depression and anxiety during the pandemic. "A lot of those diagnoses... might have been the result of a child being assessed for a different diagnosis, something like anxiety or depression, and their clinician identifying that the child also had ADHD," Danielson says.

The increase in diagnoses also comes amid growing awareness of ADHD — and the different ways that it can manifest in children. Danielson says that may help explain why girls are becoming more commonly diagnosed with ADHD compared to boys than they had been in the past. She says boys have long been diagnosed with ADHD at around two and half times the rate of girls, but the new reports finds that difference is narrowing.

Decades ago, ADHD was thought of as a disorder of hyperactivity among boys, Danielson says. "Boys will often have hyperactive or impulsive ADHD, where they'll run into the street or jump off things or do things that might make them more likely to be injured," she says.

“Girls tend to manifest their ADHD in a more inattentive way. They’ll be daydreaming or have a lack of focus or be hyper-focused on a particular task that maybe is not the task that they need to be focused on,” says Danielson.

The study, which appears in the Journal of Clinical Child & Adolescent Psychology, was based on data from the National Survey of Children's Health , which gathers detailed information from parents.

While the report found that the number of kids diagnosed with ADHD had risen since 2016, only about half of them were taking medication to treat the condition — compared with two-thirds of children back in 2016. The data didn’t look into reasons why this might be, but Danielson notes that reports of shortages of ADHD medications began around the time the data was collected.

Dr. Max Wiznitzer, a professor of pediatric neurology at Case Western Reserve University, says he suspects some parents may be reluctant to put their kids on ADHD medication out of misguided concerns. "There's the myth that it's addictive, which it's not." He says studies have shown people treated with ADHD have no increased risk of drug abuse.

Wiznitzer says medication is important because it can help kids focus by controlling symptoms of impulsivity, overactivity and inattention. But ADHD treatment also requires therapy that can teach children — and their parents — behavioral and educational strategies to manage their condition. "It's always a two-pronged approach," he says. He finds it troubling that the report found less than half of kids and adolescents diagnosed with ADHD were getting any behavioral therapy.

The report also found that nearly 78% percent of children diagnosed with ADHD had at least one other diagnosed disorder. The most common were behavioral or conduct problems, anxiety and developmental delays. Autism and depression were also frequently observed, Danielson says.

Kids with ADHD are at increased risk for other conditions including depression, anxiety and substance abuse and if left untreated, ADHD can raise the risk of serious health concerns in adulthood. This includes a higher risk of diabetes, heart disease and shortened life span, Wiznitzer says — which is why increased awareness and diagnosis is important.

Danielson says parents can also find information on treatment and services at CHADD — Children And Adults with ADHD , a non-profit resources organization where Wiznitzer serves on the advisory board.

He says parents seeking treatment for their kids should start with a conversation with their pediatrician.

This story was edited by Jane Greenhalgh.

Copyright 2024 NPR

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• Data and Statistics on ADHD
• Free Materials on ADHD
• Attention-Deficit / Hyperactivity Disorder Articles
• Clinical Care and Treatment

Clinical Care of ADHD

• The American Academy of Pediatrics (AAP) has developed a clinical practice guideline that provides recommendations for the diagnosis and treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
• This guideline is based on the best available evidence, and is intended for use by primary care providers, such as pediatricians, family physicians, and other healthcare providers.

Diagnosis and evaluation of ADHD

The AAP guidelines for diagnosis and evaluation of ADHD recommend that healthcare providers complete these steps:

• Evaluate children and adolescents ages 4 to 18 years for ADHD if they are having academic or behavioral problems and show inattention, A hyperactivity, B or impulsivity. C
• Get reports on the child's symptoms from parents or guardians, school staff, and mental health workers involved with their care, and get information from the child or adolescent as well.
• Use rating scales and other sources to document the symptoms and ensure that DSM-5 criteria have been met.
• Rule out any other possible conditions that can cause similar symptoms.
• Screen for other conditions that might coexist with ADHD, including emotional or behavioral disorders (such as anxiety, depression, and behavior problems), developmental disorders (such as learning and language disorders or autism spectrum disorder ), and physical conditions (such as tics , sleep disorders, or apnea ).
• Refer children to a specialist if they detect co-occurring conditions that they are not experienced in treating or diagnosing.

Treatment recommendations

The AAP guidelines for treatment of ADHD 1 recommend that

• Children and adolescents with ADHD should be treated the same as would any other child or adolescent with special healthcare needs, following the principles of the chronic care model and the medical home.

Did you know?‎

Aap treatment guidelines by age group, children ages 4-6 years.

The first line of treatment should include:

• Parent training in behavior management ; and/or
• Behavioral classroom interventions (if available).

ADHD medications for children ages 4-6 years‎

School-age children and adolescents.

Recommended treatment for children (6+ years) and adolescents includes:

• FDA-approved medications along with

Treatments often work best when used together.

For all children attending school, the school is a necessary part of any treatment plan . These plans can include:

• Educational interventions; and
• Individual school supports, such as school environment and behavioral supports.

School treatment plans often include an Individualized Education Program (IEP) or a 504 plan that describes accommodations.

Healthcare providers supporting children with special healthcare needs ‎

Any child or adolescent who is taking medication.

The AAP guidelines for treatment of ADHD recommend that

• The healthcare provider adjusts the patient's medication dose as needed to achieve the most benefit with the least amount of tolerable side effects.

Important note on medication prescribing and use:‎

• About ADHD | CDC
• Diagnosing ADHD | CDC
• Treatment of ADHD | CDC
• Other Concerns and Conditions with ADHD | CDC
• Inattention. Not being able to carefully complete a task, think about, listen to, or watch someone or something.
• Hyperactivity. Having an abnormally high level of activity or excitement that interferes with the ability to concentrate or interact with others.
• Impulsivity. Acting on sudden desires, whims, or feelings rather than from careful thought.
• Wolraich ML, Hagan JF Jr, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W; SUBCOMMITTEE ON CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVE DISORDER. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019 Oct;144(4):e20192528. doi: 10.1542/peds.2019-2528. Erratum in: Pediatrics. 2020 Mar;145(3).
• Agency for Healthcare Research and Quality (AHRQ). Defining the Patient Centered Medical Home. Available at: https://www.ahrq.gov/ncepcr/research/care-coordination/pcmh/define.html . Accessed on November 20, 2023
• U.S. Food & Drug Administration (FDA). Treating and dealing with ADHD. Available at: https://www.fda.gov/consumers/consumer-updates/dealing-adhd-what-you-need-know . Accessed on November 20, 2023

Attention-Deficit / Hyperactivity Disorder (ADHD)

CDC's Attention-Deficit / Hyperactivity Disorder (ADHD) site includes information on symptoms, diagnosis, treatment, data, research, and free resources.

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Approximately one in nine U.S. children diagnosed with ADHD: New study highlights growing public health concern

by Taylor & Francis

An exploration into the national U.S. dataset on children ever diagnosed with ADHD has revealed an "ongoing and ever-expanding" public health issue.

Findings published in the Journal of Clinical Child & Adolescent Psychology uncover that approximately one million more children aged 3–17 had received an ADHD diagnosis in 2022 than in 2016.

The paper reveals around one in nine children have ever received an ADHD diagnosis—11.4%, or 7.1 million children. Some 6.5 million children (10.5%) currently live with ADHD.

Among children currently living with ADHD, 58.1% have moderate or severe ADHD.

In total, 77.9% have at least one co-occurring disorder, approximately half of children with current ADHD (53.6%) had received ADHD medication, and 44.4% had received behavioral treatment for ADHD in the past year.

Nearly one-third (30.1%) did not receive any ADHD-specific treatment.

The results follow an analysis of the 2022 National Survey of Children's Health (NSCH) dataset. They demonstrate that the estimated prevalence of ADHD (based on a parent report) is higher in the United States than comparable estimates from other countries.

The authors come from institutions including the Centers for Disease Control and Prevention, the Oak Ridge Institute for Science and Education, and the Health Resources and Services Administration.

In the paper, the team explains that the increase of ADHD prevalence can partially be explained by "sociodemographic and child characteristics," while they state societal context can also "contribute to the overall trends in the diagnosis of ADHD."

These include the context around children's mental health before and during the COVID-19 pandemic.

"Public awareness of ADHD has changed over time. ADHD was historically described as an externalizing disorder with a focus on easily observable hyperactive-impulsive symptoms, and was thought to primarily affect boys," the authors say. "With increased awareness of symptoms related to attention regulation, ADHD has been increasingly recognized in girls, adolescents, and adults. Moreover, ADHD has previously been diagnosed at lower rates among children in some racial and ethnic minority groups. With increased awareness, such gaps in diagnoses have been narrowing or closing.

"Circumstances related to the pandemic may also have increased the likelihood that a child's ADHD symptoms could cause impairment. For example, in families where children needed to engage in virtual classroom learning while parents were also working from home, previously manageable ADHD symptoms may have become more impairing or symptoms that were previously unobserved by parents may have become recognizable."

The aim of this new paper was to provide updated U.S. prevalence estimates of diagnosed ADHD; ADHD severity; co-occurring disorders; and receipt of ADHD medication and behavioral treatment. The team assessed 45,483 completed interviews, also monitoring differences in demographic and clinical subgroups. Questions asked parents for details such as the severity of the condition.

Findings highlight how socioeconomic and geographic factors play a part in diagnosis/prevalence of ADHD.

For example:

• Asian and Hispanic/Latino children had a lower prevalence of diagnosed ADHD than white children.
• Children living in households with high school as the highest level of education and lower-income households had a higher prevalence than children living in households with more education and with income ≥200% of the federal poverty level , respectively.
• Children with public insurance (with or without private insurance) had a higher prevalence than children with private insurance alone.
• Prevalence was also higher for children living in the Northeast, Midwest, or South compared to those living in the West and for children living in rural or suburban areas compared to children living in urban areas.

The results also demonstrated how such factors impacted upon medicated treatment:

• Hispanic children and children living in non-English-speaking households had a lower prevalence of taking ADHD medication than non-Hispanic children and children living in primarily English-speaking homes, respectively.
• A higher prevalence of children with both public and private insurance were taking ADHD medication than children with private insurance only.
• A higher prevalence of children living in the Midwest and South were taking ADHD medication compared to children in the West.

Other behavioral treatments, such as mental health counseling, also followed similar patterns.

Explaining the findings further, the authors state, "Shifts in patterns of treatments may also be affected by changes in the demographic distribution of who receives ADHD diagnoses. There is evidence that the sex difference for diagnosis of ADHD may be narrowing; in prior years, the ratio of boys to girls diagnosed with ADHD was more than 2:1."

Concluding, the team states that they hope their findings can be used by clinicians to understand diagnosis and treatment patterns to better inform clinical practice. Additionally, they hope it could be used by policymakers, government agencies, health care systems, public health practitioners, and other partners to plan for the needs of children with ADHD, such as by ensuring access to care and services for ADHD.

Future research, the team states, could investigate patterns of service delivery during and after the pandemic; as well as modes of ADHD service delivery; uptake and discontinuation of ADHD medication; and receipt of evidence-based behavioral treatment and other recommended services such as school services.

This study is subject to a number of limitations, including it being based on a survey of parent recall and reporting decisions, and has not been validated against medical records or clinical judgment.

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ADHD is an ongoing and expanding public health concern, according to researchers studying the disorder. One million more U.S. children were diagnosed in 2022 compared to 2016, a new study shows.

A big jump: Researchers found that in 2022, 7.1 million kids and adolescents in the U.S. had received an ADHD diagnosis – a million more children than in 2016. That jump in diagnoses was not surprising, given that the data was collected during the pandemic, says Melissa Danielson, a statistician with the CDC's National Center on Birth Defects and Developmental Disabilities and the study's lead author.

Read more ... for details on the study's findings.

About 1 in 9 children in the U.S., between the ages of 3 and 17, have been diagnosed with ADHD. That's according to a new report from the Centers for Disease Control and Prevention that calls attention-deficit/hyperactivity disorder an "expanding public health concern."

Researchers found that in 2022, 7.1 million kids and adolescents in the U.S. had received an ADHD diagnosis – a million more children than in 2016. That jump in diagnoses was not surprising, given that the data was collected during the pandemic, says Melissa Danielson, a statistician with the CDC's National Center on Birth Defects and Developmental Disabilities and the study's lead author.

She notes that other studies have found that many children experienced heightened stress, depression and anxiety during the pandemic. "A lot of those diagnoses... might have been the result of a child being assessed for a different diagnosis, something like anxiety or depression, and their clinician identifying that the child also had ADHD," Danielson says.

The increase in diagnoses also comes amid growing awareness of ADHD — and the different ways that it can manifest in children. Danielson says that may help explain why girls are becoming more commonly diagnosed with ADHD compared to boys than they had been in the past. She says boys have long been diagnosed with ADHD at around two and half times the rate of girls, but the new reports finds that difference is narrowing.

Decades ago, ADHD was thought of as a disorder of hyperactivity among boys, Danielson says. "Boys will often have hyperactive or impulsive ADHD, where they'll run into the street or jump off things or do things that might make them more likely to be injured," she says.

"Girls tend to manifest their ADHD in a more inattentive way. They'll be daydreaming or have a lack of focus or be hyper focused on a particular task that maybe is not the task that they need to be focused on," says Danielson.

The study, which appears in the Journal of Clinical Child & Adolescent Psychology, was based on data from the National Survey of Children's Health , which gathers detailed information from parents.

While the report found that the number of kids diagnosed with ADHD had risen since 2016, only about half of them were taking medication to treat the condition – compared with two-thirds of children back in 2016. The data didn't look into reasons why this might be, but Danielson notes that reports of shortages of ADHD medications began around the time the data was collected.

Dr. Max Wiznitzer, a professor of pediatric neurology at Case Western Reserve University, says he suspects some parents may be reluctant to put their kids on ADHD medication out of misguided concerns. "There's the myth that it's addictive, which it's not." He says studies have shown people treated with ADHD have no increased risk of drug abuse.

Wiznitzer says medication is important because it can help kids focus by controlling symptoms of impulsivity, overactivity and inattention. But ADHD treatment also requires therapy that can teach children — and their parents — behavioral and educational strategies to manage their condition. "It's always a two-pronged approach," he says. He finds it troubling that the report found less than half of kids and adolescents diagnosed with ADHD were getting any behavioral therapy.

The report also found that nearly 78% percent of children diagnosed with ADHD had at least one other diagnosed disorder. The most common were behavioral or conduct problems, anxiety and developmental delays. Autism and depression were also frequently observed, Danielson says.

Kids with ADHD are at increased risk for other conditions including depression, anxiety and substance abuse and if left untreated, ADHD can raise the risk of serious health concerns in adulthood. This includes a higher risk of diabetes, heart disease and shortened life span, Wiznitzer says – which is why increased awareness and diagnosis is important.

Danielson says parents can also find information on treatment and services at CHADD — Children And Adults with ADHD , a non-profit resources organization where Wiznitzer serves on the advisory board.

He says parents seeking treatment for their kids should start with a conversation with their pediatrician.

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• Population Study Article
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• Published: 07 May 2024

Risk of traumatic brain injury among patients with ADHD and their unaffected siblings

• Ping-Chung Wu 1 , 2 ,
• Shih-Jen Tsai 2 , 3 ,
• Ju-Wei Hsu 2 , 3 ,
• Kai-Lin Huang 2 , 3 ,
• Tzeng-Ji Chen 4 , 5 , 6 ,
• Tai-Long Pan 7 , 8 , 9 &
• Mu-Hong Chen   ORCID: orcid.org/0000-0001-6516-1073 2 , 3  

Pediatric Research ( 2024 ) Cite this article

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Metrics details

As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear.

Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up.

Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86).

Conclusions

Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation.

ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI).

Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group.

TBI requiring hospitalization occurred more in the sibling group than in the proband group.

TBI risk should be closely monitored among unaffected siblings of patients with ADHD.

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Introduction.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder among children, with an estimated prevalence increasing from 6.1% in 1997–1998 to 10.8% in 2022 according to the National Health Interview Survey of the U.S. population. 1 , 2 ADHD often persists into adulthood and affects approximately 2.–3.4% of the adult population. 3 , 4 Individuals with ADHD mostly have symptoms of inattention, hyperactivity, impulsivity, or a combination of these symptoms, which compromise basic functions and may adversely affect subsequent mental and physical health. 5 , 6 , 7 , 8

Previous studies have demonstrated that both ADHD probands and their unaffected siblings tend to have impaired performance in a wide range of neuropsychological functions such as sustained attention and executive functions. 9 , 10 , 11 Gau and Huang assessed attention performance in ADHD probands, unaffected siblings, and healthy controls using the Rapid Visual Information Processing (RVP) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subsequently, they discovered that probands with ADHD and their unaffected siblings had significantly higher total misses and a lower probability of hits in the RVP task than controls. 9 Similarly, through analysis of the results of RVP-total hits, Pironti et al. found that cognitive impairments, especially in sustained attention, were present in both ADHD patients and their relatives. 10 Increasing evidence has suggested that unaffected siblings of ADHD probands may exhibit a common endophenotype with their ADHD siblings and exhibit some deficits in attention, working memory, behavior inhibition, and executive functions. 12 , 13 , 14

Traumatic brain injury (TBI), one of the major causes of death and disability in children, adolescents, and young adults globally, causes severe sequelae and burdens on the lives of patients, their families, and society. 15 , 16 , 17 It has been estimated that more than 1.4 million people sustain a TBI each year in the United States, of whom 50,000 die from their injuries. 18 Nguyen et al. performed a systematic review and meta-analysis of the global incidence of TBI and discovered a pooled incidence rate of 349 per 100,000 person-years for all ages. 19 With its rapidly increasing prevalence and the increasing years of life lived with disability (YLDs) globally, TBI contributes considerably to the global injury burden. 20

Several studies have suggested the potential relationship between ADHD and TBI. 21 , 22 , 23 Ilie et al. conducted a cross-sectional study of 3,993 Canadian adults and observed significant positive associations between lifetime TBI and both current and past ADHD in this population. 21 By comparing student athletes who had sustained a mild TBI with controls of similar age and sex, Biederman et al. reported that mild TBI subjects had a significantly higher rate of ADHD than controls, and that in all subjects, the onset age of ADHD was before the onset age of mild TBI. 22 Furthermore, in a retrospective cohort study, Liou et al. demonstrated that patients with ADHD had a higher incidence of TBI than controls. 23 However, few studies have investigated the likelihood of subsequent TBI development among ADHD patients, unaffected siblings of ADHD probands, and healthy controls. In a study consisting of 5,128 unaffected siblings of ADHD probands and 20,512 age- and sex-matched controls, Wei et al. observed that the unaffected siblings of patients with ADHD were more likely to develop TBI later in life compared with controls. 24 The likelihood of subsequent TBI development among ADHD patients, unaffected siblings, and healthy controls is a topic worth exploring because the relationship between ADHD and TBI is gaining increasing attention, and the fact that unaffected siblings of ADHD probands may exhibit a common endophenotype and similar cognitive impairments with their ADHD siblings should be considered. Nevertheless, further studies and understanding of this topic seem to be limited. Furthermore, the effects of ADHD medications on the risk of subsequent TBI, the severity of subsequent TBI, and the age of TBI diagnosis have been rarely discussed in previous publications.

In this longitudinal, population-based cohort study, we investigated the risk of subsequent TBI, including skull fracture, concussion, contusion, and brain hemorrhage following injury, among patients with ADHD and their unaffected siblings and assessed the effect of ADHD medications on the risk of subsequent TBI, the severity of subsequent TBI, and the age of TBI diagnosis using the Taiwan National Health Insurance Research Database (NHIRD). We hypothesized that ADHD probands may have the highest risk of subsequent TBI, followed by unaffected siblings and controls during follow-up.

Data source

Taiwan NHIRD which consists of healthcare data from >99.7% of the entire Taiwan population is audited and released by National Health Research Institute for scientific and study purposes. In current study, we linked three databases together for the analysis. The first is the registry database for all beneficiaries (~28,000,000), which was used for the genealogy reconstruction and demographic characteristics based on Chen et al’s and Cheng et al’s methods. 25 , 26 The second is the specialized dataset of mental disorders, which includes all medical (mental and non-mental) records between 2000 and 2011 of all insured individuals with mental disorders, and was used for the identification of ADHD probands. The third is the Longitudinal Health Insurance Database, which includes all medical records between 1996 and 2011 of 3,000,000 insured individuals that are randomly selected from entire Taiwanese people (~28,000,000), and was used for the identification of the unaffected siblings and control group. Individual medical records included in the NHIRD are anonymous to protect patient privacy. The diagnostic codes used were based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The NHIRD has been used extensively in many epidemiologic studies in Taiwan. 25 , 26 , 27 , 28 Institutional Review Board of Taipei Veterans General Hospital approved the study protocol and waived the requirement for informed consent since this investigation used de-identified data and no human subjects contact was required.

Inclusion criteria for patients with ADHD, unaffected siblings and the control group

Patients who had a diagnosis of ADHD (ICD-9-CM code: 314) without prior TBI history between 2001 and 2010 were identified from the specialized dataset of mental disorders. To ensure diagnostic validity, a diagnosis of ADHD was given by board-certified psychiatrists at least twice (i.e., one psychiatrist at two different time points or two different psychiatrists) according to the clinical diagnostic interview and professional judgment. Individuals who had no ADHD diagnosis at any time in the database but had any sibling with ADHD were included as the ADHD sibling cohort (unaffected sibling group). The term “unaffected” sibling was probably a group that is not meeting the threshold for ADHD diagnosis compared with the identified ADHD probands but may share some of the underlying genetic as well as environmental risk factors for ADHD. 29 , 30 , 31 The age-, sex-, birth time-, and residence-matched (1:10) control cohort was randomly identified from the Longitudinal Health Insurance Database after eliminating the study cases, those who had been given a diagnosis of ADHD at any time in the database, and those with any sibling with ADHD. Those who were diagnosed with TBI prior to January 01 2001 were excluded in the unaffected siblings and control group. The time of ADHD diagnosis was defined as the enrollment time in the ADHD proband group; January 01 2001 or the birthdate was defined as the enrollment time in the unaffected siblings and control groups. In addition, the long-term use of ADHD medications (methylphenidate or atomoxetine) during the follow-up was defined by the cumulative defined daily dose (cDDD) during the follow-up ≥ 365. 8 The DDD recommended by the World Health Organization (WHO) Collaborating Center for Drug Statistics Methodology is a unit for measuring a prescribed amount of drug. The DDD is the assumed average maintenance dose per day of a drug consumed for its main indication. We calculated the sum of the dispensed DDD (cDDD) of ADHD medications during the follow-up period. Level of urbanization (level 1 to level 5; level 1: most urbanized region; level 5: least urbanized region) was also assessed for our study. 32

Main outcomes

TBI, including fracture of skull (ICD-9-CM codes: 800 ~ 801, 803 ~ 804), concussion (ICD-9-CM code: 850), contusion (ICD-9-CM code: 851), brain hemorrhage following injury (ICD-9-CM codes: 852, 853), and unspecified intracranial injury (ICD-9-CM codes: 854, 959.01), was identified during the follow-up (from enrollment to December 31 2011 or to the death). In addition, TBI requiring hospitalization was also identified.

Statistical analysis

For between-group comparisons, the F test was used for continuous variables and Pearson’s X2 test for nominal variables, where appropriate. Cox regression models with adjustment of age, sex, residence and income were used to examine the hazard ratios (HRs) and 95% confidence intervals (CIs) of subsequent TBI and TBI requiring hospitalization in ADHD probands and unaffected siblings compared with the control group. Furthermore, we assessed the TBI and TBI requiring hospitalization likelihoods among ADHD probands with and without long-term use of ADHD medications, unaffected siblings, and control group. A 2-tailed P value of less than 0.05 was considered statistically significant. All data processing and statistical analyses were performed with Statistical Package for Social Science (SPSS) version 17 software (SPSS Inc.) and Statistical Analysis Software (SAS) version 9.1 (SAS Institute, Cary, NC).

In all, 18,645 patients with ADHD, 18,880 unaffected siblings of such patients, and 188,800 age-/sex-matched controls were included in our study. Patients with ADHD (4.48 ± 4.99 years) were younger than the other two groups (~ 6 years, p  < 0.001) (Table  1 ). The ADHD proband group was male predominant (79.7%). During the follow-up, the ADHD probands had the highest incidence of developing any TBI (18.9%, p  < 0.001), while the unaffected siblings had the highest incidence of developing TBI requiring hospitalization (1.5%, p  = 0.005) (Table  1 ). TBI occurred younger in patients with ADHD (8.97 ± 6.15 years) and unaffected siblings (9.85 ± 7.24 years) than in the control (10.17 ± 7.59 years, p  < 0.001) (Table  1 ). However, the TBI events took longer to occur in the ADHD proband group (4.56 ± 3.17 years) than in the other two groups (4.04 ± 2.84 years in unaffected siblings, 4.15 ± 2.88 years in the control group, p  < 0.001) (Table  1 ).

Kaplan-Meier survival analyses with the log-rank tests of any TBI ( p  < 0.001) and TBI requiring hospitalization ( p  < 0.001) risks between groups were shown in the Fig.  1 . The Cox regression models with full adjustment of age, sex, income, and level of urbanization showed that the patients with ADHD (HR: 1.57, 95% CI: 1.51–1.63) and the unaffected siblings of such patients (HR: 1.20, 95% CI: 1.15–1.25) were more likely to develop any TBI during the follow-up than the control group (Table  2 ). Surprisingly, the unaffected siblings (HR: 1.21, 95% CI: 1.07–1.37) were more likely, while the ADHD probands (HR: 0.86, 95% CI: 0.75–1.00) were less likely, to develop TBI requiring hospitalization during the follow-up compared with the control group (Table  2 ).

ADHD attention deficit hyperactivity disorder, TBI traumatic brain injury.

Finally, the long-term use of ADHD medications may slightly reduce the risk of any TBI occurrence (HR: 1.44, 95% CI: 1.30–1.60) during the follow-up compared with the short-term use (1.59, 1.53–1.65) among patients with ADHD (Table  2 ).

The results of this large-scale, population-based study supported the hypothesis that ADHD probands had the highest risk of subsequent TBI during the follow-up period, followed by unaffected siblings and healthy controls. In addition, we observed a counter-intuitive result that unaffected siblings had a higher risk of TBI requiring hospitalization than did healthy controls, whereas ADHD probands had a lower risk than controls. Furthermore, our findings suggest that the use of ADHD medications may reduce the risk of subsequent TBI requiring hospitalization, and the results demonstrated an earlier mean age at TBI diagnosis in ADHD probands and unaffected siblings than in controls.

As mentioned in the introduction, the potential relationship between ADHD and TBI has been suggested in several studies. 21 , 22 , 23 However, a meta-analysis comprising 3023 mild TBI patients and 9,716 controls revealed a significant association between ADHD and mild TBI, and the association was significant in studies that have reported on ADHD subsequent to mild TBI, but not in studies that have reported mild TBI subsequent to ADHD. 33 As TBI can exacerbate attention and impulsivity problems, 34 the relationship between ADHD and TBI could become bidirectional and complicated. Moreover, both ADHD and TBI are associated with a wide range of negative outcomes; thus, clarifying the temporal association is essential for developing effective prevention and treatment measures. In a prospective longitudinal study that examined the TBI diagnosis records of 628 male patients from birth to the age of 34 years, Guberman et al. discovered that childhood inattention-hyperactivity assessed using teacher rating scales was significantly associated with an increased risk of TBI from the ages of 11–34 years. 35 Asarnow et al. conducted a meta-analysis of 12,374 patients with TBI of all severity levels and 43,491 controls and reported that 16.0% of patients with TBI presented with ADHD before brain injury; the prevalence of severe TBI was considerably higher than that of 10.8% reported for the general population. 36 As increasing studies have supported the relationship between ADHD and subsequent TBI, 21 , 22 , 23 , 35 , 36 our study discovered a similar mean duration of 4.56 years between study enrollment and subsequent TBI development among ADHD patients. Therefore, because ADHD appears to be a risk factor for TBI, more attention should be paid to this high-risk population. Although studying whether TBI is a risk factor for ADHD is a crucial topic, it is not addressed in this study.

According to previous studies that have assessed ADHD patients, unaffected siblings of ADHD probands, and healthy controls using psychiatric interviews and different executive function tasks, unaffected siblings of ADHD probands may exhibit a common endophenotype with their ADHD siblings, and they may also exhibit some deficits in a wide range of neuropsychological functions. 9 , 10 , 11 , 12 , 13 In addition, several neuroimaging studies have examined neuroanatomical abnormalities in ADHD patients and their unaffected siblings. 10 , 37 , 38 , 39 , 40 Pironti et al. found an abnormal decrease in the gray matter volume in the right inferior frontal gyrus and an abnormal increase in the white matter volume in the caudal portion of the right inferior fronto-occipital fasciculus among ADHD patients and their unaffected first-degree relatives. 10 Hoogman et al. compared unaffected siblings with healthy controls and demonstrated shared familial effects by showing a significantly smaller surface area in the caudal middle frontal, lateral orbital frontal, and superior frontal gyrus in unaffected siblings. 37 Chiang et al. reported increased functional connectivity in the left insula and left inferior frontal gyrus among both ADHD probands and unaffected siblings compared with controls. 38 These studies have provided evidence that neural profiles are shared between ADHD patients and their unaffected siblings, and the results suggest that some of the shared neuroanatomical abnormalities may be associated with the severity of ADHD symptoms in unaffected siblings. 37 , 40 To summarize, neuropsychological and neuroanatomical abnormalities found in ADHD probands and unaffected siblings may lead to the partial expression of ADHD symptoms and further adversely affect their subsequent mental and physical health. 6 , 7 , 24 Although the relationship between ADHD and TBI has been examined in previous research, 21 , 22 , 23 , 33 , 35 , 36 the association between TBI and unaffected siblings of ADHD probands has been rarely discussed. Wei et al. reported that unaffected siblings of ADHD probands were more likely to develop TBI (OR: 1.24, 95% CI: 1.14–1.36) than controls. 24 Our study data also revealed this finding. Consequently, unaffected siblings and ADHD probands appear to be a high-risk population for TBI; thus, increasing the awareness of the increased TBI risk for their families and caregivers is warranted.

The severity of TBI has often been considered when exploring the relationship between TBI and subsequent ADHD. 33 , 36 , 41 However, fewer studies have considered the severity of TBI because more studies are focusing on the association between ADHD and subsequent TBI development. In this study, we also considered the severity of TBI by identifying TBI requiring hospitalization. The results revealed that when compared with controls, unaffected siblings were at a higher risk of TBI requiring hospitalization, whereas ADHD probands were at a lower risk. By using the German Pharmacoepidemiological Research Database, Lindemann et al. performed a large-scale retrospective cohort study to assess the risk of hospitalization due to injury diagnoses in children and adolescents with newly diagnosed ADHD compared with those without ADHD, 42 and the results were different from our findings. Moreover, they reported that the incidence of TBI hospitalization was 1.87% (95% CI: 1.71–2.04) in male ADHD patients, 1.32% (95% CI: 1.19–1.47) in male controls, 1.38% (95% CI: 1.15–1.65) in female ADHD patients, and 0.91% (95% CI: 0.73–1.13) in female controls, with an increased adjusted HR of TBI hospitalization for patients with ADHD compared with those without. By contrast, our study reported that the incidence of TBI requiring hospitalization was 1.1% in ADHD patients and 1.3% in healthy controls, with a decreased adjusted HR of TBI requiring hospitalization for ADHD probands compared with controls. To explain the differences, we proposed the following possible reasons. The differences may be attributed to some biological, psychological, and sociological factors that were not investigated but could influence the incidence rates. For instance, Lindemann et al. did not consider the ADHD medication treatment as a possible protective factor against TBI in ADHD patients; however, the factor was discussed further in the study. Consequently, the results are potentially confounded by the fraction of patients receiving ADHD medications. In addition, other unmeasured potential prognostic factors, such as socioeconomic status, psychological stress, and environmental safety, may influence the results and contribute to the differences. Due to the limited relevant literature, further studies are required to reveal more details. Moreover, our study discovered a counter-intuitive and surprising result that ADHD probands had a decreased risk of TBI requiring hospitalization compared with healthy controls, which might be because ADHD probands may be in a safer setting, be under more protection, and receive more care from caregivers given their diagnosis of ADHD than other healthy individuals. The aforementioned reasons may also explain our finding of the longest duration between enrollment and TBI occurrence in the ADHD probands compared with the other two groups. Nevertheless, these measures to prevent ADHD patients from physical injuries have some limitations because of the increased TBI risk among ADHD patients shown in this study, but they may play an important role in reducing their risk of TBI hospitalization. The beneficial effect of the use of ADHD medications on subsequent TBI requiring hospitalization could also explain the difference. However, the result should be interpreted with caution, and further studies are needed to confirm the hypothesis. Additionally, our study reported that the unaffected siblings of ADHD probands were more likely to develop both TBI and TBI requiring hospitalization than healthy controls. Hence, we recommend that more attention be paid to preventing subsequent TBI development in this population.

Previous studies have revealed that ADHD medications are related to decreases in the risks of a wide range of ADHD-associated functional outcomes, including TBI and accidents and injuries. 23 , 43 , 44 , 45 , 46 , 47 Mikolajczyk et al. demonstrated a 34% risk reduction for hospitalization due to brain injury diagnoses during the periods with ADHD medication compared with nonmedicated periods. 45 Liou et al. examined 72,181 ADHD patients and 72,181 age-and sex-matched non-ADHD controls and reported the association between the long-term use of ADHD medications and a reduced risk of subsequent TBI. 23 Boland et al. conducted a meta-analysis of 21 studies in 2020 and revealed a robust protective effect of ADHD medications on academic outcomes, accidents and injuries, and mood disorders, along with a statistically insignificant protective effect on TBI. 46 More recently, Brunkhorst-Kanaan et al. conducted a systematic review and suggested that stimulant medication appeared to be effective for injury prevention in ADHD patients over their lifespan. 47 Compatible with the results of previous studies, our study results suggest that the use of ADHD medications may reduce the risk of subsequent TBI requiring hospitalization. Therefore, early diagnosis and optimal treatment for individuals with ADHD are critical in clinical practice to minimize the risk of subsequent TBI requiring hospitalization. In addition, further well-designed clinical studies may be needed to quantify the protective effects of ADHD medications on subsequent TBI risk.

Age at TBI diagnosis may influence neurocognitive, academic, and behavior outcomes following TBI and is a topic worth exploring. 48 , 49 , 50 , 51 , 52 , 53 However, previous studies have reported mixed results. Some studies have supported the theory of neuroplasticity describing that children injured at an earlier age have better outcomes due to the ability for neuronal circuits in the young brain to undergo adaptive changes on structural and functional levels, 51 , 52 whereas other studies have supported the theory of vulnerability stating that children injured at an earlier age have poorer outcomes because of the incomplete development of the brain after TBI. 48 , 49 , 50 , 53 The impact of age at TBI diagnosis on the results is difficult to assess because of the increasing difficulty of detecting neurocognitive impairments in younger children, the lack of large-scale studies, and variations in the distribution of age categories and the timing of follow-up evaluations in various studies. 54 , 55 In this study, we collected a wide range of demographic data on age at TBI diagnosis from a considerably large-sized sample. In addition, we observed an earlier mean age at TBI diagnosis in ADHD probands and unaffected siblings compared with controls. However, the impact of age at injury on outcomes following TBI remains controversial; therefore, further studies are necessary to corroborate this finding.

However, this study has several limitations. First, the incidence of TBI and TBI requiring hospitalization may have been underestimated because only those who seek medical help are registered in the NHIRD. Second, information on the severity of ADHD and TBI is unavailable in the NHIRD. Therefore, we did not account for the severity of ADHD and identified TBI requiring hospitalization as an alternative way to assess the severity of TBI. Further studies would be required to clarify the association of ADHD diagnosis and trait with the exact severity, which was defined by the TBI neuroimaging criteria and Glasgow Coma Scale, of TBI. Finally, because the NHIRD does not provide information on factors such as psychosocial stress, family relationships, personal lifestyle, and environment, we could not explore their influence. Therefore, these limitations should be considered when interpreting the results.

In conclusion, this large-scale, population-based study suggested that ADHD probands had the highest risk of subsequent TBI, followed by their unaffected siblings and controls. We also found that unaffected siblings had a higher risk of TBI requiring hospitalization than controls, whereas ADHD probands had a lower risk. Hence, we recommend that more attention should be paid in order to prevent subsequent TBI development in the unaffected siblings of ADHD probands. In addition, this study demonstrated that the use of ADHD medications may reduce the risk of subsequent TBI requiring hospitalization, which supports the importance of early diagnosis and optimal treatment for individuals with ADHD.

Data availability

The NHIRD was released and audited by the Department of Health and Bureau of the NHI Program for the purpose of scientific research ( https://www.apre.mohw.gov.tw/ ). The NHIRD can be accessed through a formal application that is regulated by the Health and Welfare Data Science Center of Ministry of Health and Welfare, Taiwan.

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Acknowledgements

We thank Mr. I-Fan Hu, MA (Courtauld Institute of Art, University of London; National Taiwan University) for his friendship and support. Mr. Hu declares no conflicts of interest.

The study was supported by grant from Taipei Veterans General Hospital (V111C-010, V111C-040, V111C-029), Yen Tjing Ling Medical Foundation (CI-109-21, CI-109-22, CI-110-30) and Ministry of Science and Technology, Taiwan (MOST110-2314-B-075-026, MOST110-2314-B-075-024 -MY3, MOST 109-2314-B-010-050-MY3, MOST111-2314-B-075 -014 -MY2, MOST 111-2314-B-075 -013). The funding source had no role in any process of our study. Open Access funding enabled and organized by National Yang Ming Chiao Tung University.

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Ping-Chung Wu

Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Ping-Chung Wu, Shih-Jen Tsai, Ju-Wei Hsu, Kai-Lin Huang & Mu-Hong Chen

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

Shih-Jen Tsai, Ju-Wei Hsu, Kai-Lin Huang & Mu-Hong Chen

Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Tzeng-Ji Chen

Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan

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School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan

Tai-Long Pan

Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan

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Drs MHC, TLP and SJT designed the study; Drs MHC and PCW drafted the manuscript; Dr MHC analyzed the data; Drs JWH, KLH, and TJC reviewed the literature and critically reviewed the manuscript. All authors contributed substantially to the manuscript, and approved the final manuscript for submission. All authors are responsible for the integrity, accuracy and presentation of the data.

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Wu, PC., Tsai, SJ., Hsu, JW. et al. Risk of traumatic brain injury among patients with ADHD and their unaffected siblings. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03233-0

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ADHD diagnoses are rising. 1 in 9 U.S. kids have gotten one, new study finds

About 1 in 9 children in the U.S., between the ages of 3 and 17, have been diagnosed with ADHD. That's according to a new report from the Centers for Disease Control and Prevention that calls attention-deficit/hyperactivity disorder an "expanding public health concern."

Researchers found that in 2022, 7.1 million kids and adolescents in the U.S. had received an ADHD diagnosis – a million more children than in 2016. That jump in diagnoses was not surprising, given that the data was collected during the pandemic, says Melissa Danielson, a statistician with the CDC's National Center on Birth Defects and Developmental Disabilities and the study's lead author.

She notes that other studies have found that many children experienced heightened stress, depression and anxiety during the pandemic. "A lot of those diagnoses... might have been the result of a child being assessed for a different diagnosis, something like anxiety or depression, and their clinician identifying that the child also had ADHD," Danielson says.

The increase in diagnoses also comes amid growing awareness of ADHD — and the different ways that it can manifest in children. Danielson says that may help explain why girls are becoming more commonly diagnosed with ADHD compared to boys than they had been in the past. She says boys have long been diagnosed with ADHD at around two and half times the rate of girls, but the new reports finds that difference is narrowing.

Decades ago, ADHD was thought of as a disorder of hyperactivity among boys, Danielson says. "Boys will often have hyperactive or impulsive ADHD, where they'll run into the street or jump off things or do things that might make them more likely to be injured," she says.

"Girls tend to manifest their ADHD in a more inattentive way. They'll be daydreaming or have a lack of focus or be hyper focused on a particular task that maybe is not the task that they need to be focused on," says Danielson.

The study, which appears in the Journal of Clinical Child & Adolescent Psychology, was based on data from the National Survey of Children's Health , which gathers detailed information from parents.

While the report found that the number of kids diagnosed with ADHD had risen since 2016, only about half of them were taking medication to treat the condition – compared with two-thirds of children back in 2016. The data didn't look into reasons why this might be, but Danielson notes that reports of shortages of ADHD medications began around the time the data was collected.

Dr. Max Wiznitzer, a professor of pediatric neurology at Case Western Reserve University, says he suspects some parents may be reluctant to put their kids on ADHD medication out of misguided concerns. "There's the myth that it's addictive, which it's not." He says studies have shown people treated with ADHD have no increased risk of drug abuse.

Wiznitzer says medication is important because it can help kids focus by controlling symptoms of impulsivity, overactivity and inattention. But ADHD treatment also requires therapy that can teach children — and their parents — behavioral and educational strategies to manage their condition. "It's always a two-pronged approach," he says. He finds it troubling that the report found less than half of kids and adolescents diagnosed with ADHD were getting any behavioral therapy.

The report also found that nearly 78% percent of children diagnosed with ADHD had at least one other diagnosed disorder. The most common were behavioral or conduct problems, anxiety and developmental delays. Autism and depression were also frequently observed, Danielson says.

Kids with ADHD are at increased risk for other conditions including depression, anxiety and substance abuse and if left untreated, ADHD can raise the risk of serious health concerns in adulthood. This includes a higher risk of diabetes, heart disease and shortened life span, Wiznitzer says – which is why increased awareness and diagnosis is important.

Danielson says parents can also find information on treatment and services at CHADD — Children And Adults with ADHD , a non-profit resources organization where Wiznitzer serves on the advisory board.

He says parents seeking treatment for their kids should start with a conversation with their pediatrician.

This story was edited by Jane Greenhalgh.

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The kids are not all right.

A new report from the Centers for Disease Control and Prevention reveals a staggering uptick in ADHD, or attention-deficit/hyperactivity disorder , diagnoses among American children.

Calling ADHD an “expanding public health concern,” researchers found that 1 in 9 children aged 3-17 had been diagnosed with the disorder, symptoms of which include trouble paying attention, overactivity and impulsive behaviors.

The study, which appears in the  Journal of Clinical Child & Adolescent Psychology,  found that between 2016 and 2022, ADHD diagnoses among kids jumped by more than one million.

Melissa Danielson, a statistician with the CDC’s National Center on Birth Defects and Developmental Disabilities, attributes the increase to the mental toll of the pandemic. “A lot of those diagnoses … might have been the result of a child being assessed for a different diagnosis, something like anxiety or depression and their clinician identifying that the child also had ADHD,” she said.

Indeed, the report found that nearly 78% percent of children diagnosed with ADHD had at least one other diagnosed disorder. Common among these additional diagnoses were behavioral or conduct problems, anxiety, developmental delays, autism and/or depression.

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Danielson notes that ADHD was originally thought of as a hyperactive disorder that affected boys. While it is now understood to affect both genders equally, symptoms express themselves differently.

She explains, “Boys will often have hyperactive or impulsive ADHD, where they’ll run into the street or jump off things or do things that might make them more likely to be injured. Girls tend to manifest their ADHD in a more inattentive way. They’ll be daydreaming or have a lack of focus or be hyperfocused on a particular task that maybe is not the task that they need to be focused on.”

While the number of children diagnosed with ADHD has risen, the report found that only about half were treating the condition with medication, as opposed to two-thirds in 2016. Danielson explains that this drop-off may be due to shortages in ADHD meds when the data was collected.

Dr. Max Wiznitzer,  a professor of pediatric neurology at Case Western Reserve University, suspects the decline in medication may also be the result of parental reluctance. “There’s the myth that it’s addictive, which it’s not,” he said. Wizniter argues that studies have shown people treated with ADHD have no increased risk of drug abuse.

Meanwhile, an unrelated study found that between 2000 and 2021 , the number of calls to US poison control centers for children’s ADHD medication errors jumped 300%, and a University of Michigan study revealed that 1 in 4 middle and high school students are  abusing stimulants prescribed for ADHD . Additionally, ADHD medications are known to cause side effects like headache and loss of appetite.

Wiznitzer is a proponent of ADHD medication because he believes it can help control the symptoms of overactivity and inattention and aid focus. Left untreated in childhood, ADHD is known to raise the risk of diabetes, heart disease and shortened life span in adults, which is why Wiznitzer advocates for increased awareness and diagnosis.

ADHD is typically treated with a combination of behavior therapy and medication, but the report found less than half of kids and adolescents diagnosed with ADHD were getting behavioral therapy.

Recent research suggests that beyond medication, the use of behavioral therapy, in conjunction with nonpharmacological treatment , including noninvasive brain stimulation, may very well be the wave of the future for treating ADHD.

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• J Pediatr Pharmacol Ther
• v.29(2); 2024 Apr
• PMC11001204

Diagnosis and Treatment of ADHD in the Pediatric Population

Lea s. eiland.

Department of Pharmacy Practice (LSE), Auburn University Harrison College of Pharmacy;

Brooke L. Gildon

Department of Pharmacy Practice (BLG), Southwestern Oklahoma State University College of Pharmacy.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016–2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. 1 , 2

Prevalence. Attention-deficit/hyperactivity disorder begins in childhood. 1 Worldwide prevalence in children is approximately 7.2% based on population surveys. 1 Parent-reported data from the 2016–2019 US National Survey of Children’s Health (NSCH) estimates that 9.8% (approximately 6 million) of children age 3 to 17 years had ever received a diagnosis of ADHD and 8.7% currently had the disorder. 3 , 4 By age, adolescents who ever had ADHD are the highest at 13% (3.3 million). Children aged 6 to 11 years are 10% (2.4 million) and 2% (265,000) of children 3 to 5 years follow. State prevalence of ADHD varies. The NSCH found a range of 6.1% to 16.3% (median 10.5%) for children who ever had ADHD and 5.3% to 14.4% for those with a current diagnosis. 3 , 5 California, Hawaii, Nebraska, Nevada, New Jersey, New York, and South Dakota had estimates significantly lower than the rest of the country while Alabama, Arkansas, Delaware, Georgia, Indiana, Kentucky, Louisiana, Maine, Mississippi, New Hampshire, North Carolina, Ohio, South Carolina, Tennessee, and West Virginia had estimates higher compared with the rest of the country. 5 The prevalence of ADHD in males (13.3%) is more than twice that in females (6.1%). 3 The highest prevalence of ADHD is seen in Black, non-Hispanic (12%) and White, non-­Hispanic (10.9%) populations while the lowest prevalence is in the Asian, non-Hispanic (2.6%) and Hispanic (7.5%) populations. ADHD is more common in children in rural areas compared with urban or suburban areas. Patients categorized as being in the lowest federal poverty level and having public insurance also have a higher prevalence of ADHD.

Etiology. The exact cause and risk factors for ADHD are unknown; however, the heritability of ADHD is increased in first-degree relatives of a patient with ADHD with an estimate of 74%. 1 , 2 , 6 The involvement of dopaminergic and adrenergic neurotransmitters in ADHD continues to be studied as medication ­affecting these neurotransmitters are the most effective first-line pharmacotherapy. 6 Environmental factors may also play a role in ADHD. Prenatal exposure to smoking has been associated with ADHD and patients who have a very low birth weight and degree of prematurity have an increased risk for ADHD. 1

Diagnosis. There are 3 subtypes of ADHD. Patients are categorized as predominately inattentive, predominately hyperactive/impulsive, or combined (involving symptoms from both inattention and hyperactivity/impulsivity domains). For ADHD diagnosis, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), patients must have 6 or more of the 9 symptoms in the inattention domain, hyperactivity/impulsivity domain, or both domains for at least 6 months ( Table 1 ). 1 Hyperactivity is the primary symptom in preschool age children with inattention being prominent during ages 5 to 9 years. More subtle signs of hyperactivity are noted in the adolescent population such as fidgeting or feelings of restlessness, impatience, or jitteriness. Despite age, symptoms must negatively affect academic/occupational and social activities and not be consistent with the development level of the patient. Adolescents only require 5 symptoms in a domain for diagnosis. Symptoms should be present before the age of 12 years and occur in 2 or more settings (home, school, work, socially, etc) for diagnosis. Lastly, for diagnosis, symptoms must clearly interfere with or decrease the quality of academic/occupational or social activities and not be better supported by another psychotic or mental disorder diagnoses. Mild ADHD is classified in the DSM-5-TR as the patient having “few, if any, symptoms in excess of those required to make the diagnosis are present, and symptoms result in no more than minor impairments in social or occupational functioning.” 1 Severe ADHD is classified “many symptoms in excess of those required to make the diagnosis, or several symptoms that are particularly severe, are present, or the symptoms result in marked impairment in social or occupational functioning.” Moderate severity is described as symptoms or impairment between the mild and severe classifications.

DSM-5-TR Attention-Deficit/Hyperactivity Disorder Symptoms by Domain 1 *

Patients with ADHD frequently have comorbid disorders. 1 Half of children with the combined subtype and approximately one-fourth of children with the predominantly inattentive subtype will also present with oppositional defiant disorder. About one-fourth of children and adolescents with combined subtype will have conduct disorder. Autism spectrum disorder, obsessive-compulsive disorder, and tic disorders can occur concomitantly with ADHD. It is recommended by the American Academy of Pediatrics (AAP) to screen for comorbid conditions in a child or adolescent with ADHD. 7

Rating Scales. Several ADHD clinical questionnaires and rating scales based on the DSM are ­available to assist clinicians with diagnosis and follow-up assessments after therapy is initiated. The use of parent-reported or teacher-reported behavior-rating scales began in the late 1960s. 6 Today, there are clinician-, parent-, self-, and teacher-reported rating scales. The ADHD Rating Scales, Conners Rating Scales, and National Institute for Children’s Health Quality Vanderbilt Assessment Scales are commonly used in practice for preschool-age children to adolescents. Clinicians should ensure they are using the appropriate rating scale for the patient’s age, the person completing the scale, and purpose. The scales assist with ADHD diagnosis by converting subjective symptom information into objective data and then allow an objective manner for follow-up. The scale can also identify the subtype of ADHD. Providers can compare the objective outcomes to prior ratings to evaluate for symptom improvement or worsening over time. Additionally, the provider can objectively evaluate symptoms in different settings if the parent and teacher complete forms.

Guidelines. Several guidelines are available to assist clinicians with the diagnosis and treatment of ADHD in the pediatric population. 7 – 9 The AAP first begin publishing pediatric guidelines for ADHD in 2000. 7 The most current guideline was released in 2019 and provides incremental updates, a process of care algorithm, and a companion article on systemic barriers to the care of pediatric patients (4 to 18 years of age) with ADHD. 7 The AAP guidelines recommend ADHD diagnosis is based on the DSM-5 criteria. Their recommended first-line treatment for ADHD in preschool-aged children (age 4 years to the sixth birthday) includes evidence-based parent training in behavior management (PTBM) and/or behavioral classroom interventions. 7 Methylphenidate can be initiated if behavioral interventions fail to significantly improve symptoms and functioning continues to be impaired during ages 4 to 5 years. For children ages 6 years to the 12th birthday, first-line treatment for ADHD includes a Food and Drug Administration (FDA)-approved medication and/or PTBM and/or behavioral classroom interventions, with both behavioral therapies being preferred as an adjunct to medication therapy. First-line ADHD therapy for adolescents (age 12 years to the 18th birthday) is treatment with a FDA-approved medication with the patient’s assent. Evidenced-based training interventions and/or behavioral interventions are encouraged. Stimulants are the recommended first-line medication therapy due to their efficacy and strength of evidence.

The American Academy of Child and Adolescent Psychiatry first published an ADHD practice parameter in 1997 and issued their most recent parameter in 2007. 8 Treatment recommendations are similar to the AAP guidelines. The Society for Developmental and Behavioral Pediatrics published “Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents with Complex Attention-Deficit/Hyperactivity Disorder” in 2020. 9 This was the first guideline from the Society of which they described the intention of the work to complement the AAP guidelines. “Complex ADHD” is defined based on age (presentation at <4 years or >12 years), presence or suspicion of coexisting conditions, moderate to severe impairment in daily living function, uncertainty of diagnosis, or inadequate response to treatment. This guideline provides psychosocial (behavioral, educational, and psychological interventions), pharmacological treatment recommendations, and information regarding therapy for ADHD and comorbid conditions.

The AAP also has a 2014 clinical report regarding ADHD and substance abuse and a world consensus statement was published in 2023 on treating patients with ADHD and substance use disorder. 10 , 11

The European National Institute for Health and Care Excellence (NICE) ADHD guidelines were released in 2008 with the most recent update published March 2018. 12 Two additional amendments were released in 2018 and 2019. Group-parent training programs, individual-parent training programs, and cognitive behavioral therapy are recommended for patients and carers depending on the age of the patient. For patients 5 years of age and older, methylphenidate, lisdexamfetamine, and atomoxetine or guanfacine are recommended in this order. The Canadian ADHD Practice Guidelines were first released in 2006 with the current fourth edition released in 2018. 13 A multimodal treatment plan including psychosocial therapy and medications is recommended. Long-acting stimulants are recommended as first-line agents with atomoxetine, guanfacine extended release (XR) and short or intermediate-acting stimulants as second-line. Third-line agents recommended are bupropion, clonidine, imipramine, and modafinil. Both NICE and Canadian guidelines recommend the DSM-5-TR criteria for ADHD diagnosis and also include recommendations for the treatment of adults. 12 , 13

Non-Pharmacological Therapies

Behavioral therapy is strongly recommended for parents of and patients with ADHD. Examples of evidence-based behavioral and educational interventions include PTBM, behavioral classroom management, behavioral peer intervention, and individualized instructional support (e.g., instructional and class placement, Individualized Education Program, or rehabilitation plan). 7 , 9 Many PTBM pre-school programs are group programs. 7 Behavioral classroom interventions are also recommended if the child attends pre-school. Older children can additionally complete organizational skills training. 9 Behavioral parent and classroom training have positive outcomes in preadolescent children. 7 For adolescents with ADHD, PTBM may involve parents and adolescents in sessions and training focusing on school functioning skills is effective. For the adolescent, training that is continued over time, has frequent and constructive feedback, and is targeted at specific behaviors has the greatest benefit. 7 Additionally, in children and adolescents, psychosocial interventions such as behavioral therapy and training interventions have been effective. Training in social skills has not demonstrated benefit for children with ADHD. 7 Outcomes from behavioral therapies tend to continue even after therapy ends.

Digital therapeutics have emerged as a therapy for ADHD. One systematic review and meta-analysis of video game-based therapeutic interventions found that it was effective in decreasing ADHD symptoms and improving cognitive areas. 14 Typically these games focus on cognitive training such as improving attention, memory, reaction time, cognitive flexibility, or motor ability. Patients were found to have a high engagement with the games as there were low rates of dropouts from the studies. Another systematic review and meta-analysis found that digital therapeutics improved inattention and hyperactivity/impulsivity symptoms compared with control but medication improved inattention and significantly improved hyperactivity/impulsivity better than game-based digital therapeutics. 15 EndeavorRx was the first game-based digital therapeutic device approved by the FDA to improve attention function in children 8 to 12 years of age with ADHD (primarily inattentive or combined-type). 16 This approval in 2020 was the first type of game-based FDA approval for any disease or condition. It is available only via prescription and should be part of a comprehensive patient treatment plan.

Pharmacologic Treatments

US Food and Drug Administration-approved medications for the treatment of ADHD include stimulant and non-stimulant options. 1 , 7 The stimulants are described in 2 classes, methylphenidate and amphetamine. Atomoxetine, viloxazine, guanfacine, and clonidine represent non-stimulant choices commonly used in the management of ADHD. Stimulants have an effect size of 1 for treating ADHD, while non-stimulants (atomoxetine and extended-released guanfacine and clonidine) have an effect size of 0.7. 7 Bupropion, may be used off-label in patients non-responsive or unable to take an FDA-approved agent, or with a coexisting mental health diagnosis. 17 The initial medication therapy choice depends on several factors. Some general considerations include duration of desired coverage, ability of the patient to swallow solid dosage forms, time(s) of day when target symptoms occur, pharmacokinetic properties of the dosage formulation, desire to avoid administration at school, coexisting disorder or condition, potential adverse effects, history of substance abuse, preference of patient/caregiver, and medication expense and availability.

Stimulants. The stimulant class is recommended first-line in the management of ADHD due to the extensive evidence of efficacy and a known safety profile. 1 , 7 , 18 Stimulants work by blocking the presynaptic reuptake of norepinephrine and dopamine, with amphetamine also increasing the presynaptic release of dopamine and serotonin. Some areas of the brain known to show neurotransmitter impact include striatal dopamine transporters and norepinephrine transporters in the frontal lobes. 19 Both methylphenidate and amphetamine improve the core symptoms of ADHD, hyperactivity/impulsivity, and inattention, and have also shown improvements in academic functioning and a decreased risk of unintentional injuries, motor vehicle accidents (among male patients), and criminal acts. 7 , 18

The AAP clinical practice guideline does not specify which stimulant class is more effective nor name a preferred starting product as part of the standards of care. 7 Studies have found amphetamines to have better response rates at the group level when compared with methylphenidate and the non-stimulants. 18 Yet, at the patient level, participants had equally good response to both amphetamine and methylphenidate. Another systematic review found amphetamine, as compared with methylphenidate, to be slightly more efficacious in reducing core ADHD symptoms in children and adolescents, yet methylphenidate was better tolerated. 17 Based on both safety and efficacy data in children, and what is commonly seen in practice, it is prudent to start with methylphenidate and reserve amphetamines for future needs.

When selecting a long-acting stimulant product, the clinician should match the pharmacokinetic profile of the medication dosage form to the needs of the patient. Duration of efficacy should match the duration needed for symptom control. However, based on the pharmacokinetic design of the medication formulation, the drug release profile should be matched to the patient’s needs. For example, a patient who has more severe symptoms in the morning may need a product that is 50% immediate release compared with one that is 22% immediate release. It is important to remember that increasing a dose to increase efficacy can increase adverse effects as well; thus, changing products to a different pharmacokinetic profile may provide improved efficacy without additional adverse effects. Additionally, a patient who has more late afternoon/early evening symptoms may do better with a product that 70% to 80% of the dose is released in the second pharmacokinetic release to provide longer lasting efficacy of symptoms compared with a dose that provided 50% for the second release. Tables 2 and ​ and3 3 provide pharmacokinetic and dosage formulation information for the stimulants. 20 – 39 Lastly, most stimulant products are not interchangeable on a milligram-for-milligram basis and may require a taper off/on when a change of agents is required. Product medication labeling should always be referenced for guidance regarding equivalence and/or a process for conversion, if available.

Methylphenidate-based Stimulants 20 – 29

Amphetamine-based Stimulants 20 – 22 , 30 – 39

ODT, oral dissolving tablet

Across the stimulant class, proper baseline and periodic monitoring of safety/adverse events are paramount. 7 , 18 , 40 Table 4 highlights variables to monitor, frequency of monitoring, and important points to consider. 7 , 12 , 18 , 40 Also, critical to drug selection is the medication adverse effect profile. Table 5 shows common stimulant adverse events and suggested management strategies. 7 , 18 In the end, stimulant selection within ADHD management is patient-specific with a balance of efficacy, safety, and management of medication adverse events.

Recommended Monitoring for Stimulant Medications 7 , 12 , 18 , 40

Stimulant Adverse Events and ­Management 7 , 18

A final consideration with the stimulant class is related to serious risks with misuse, abuse, addiction, overdose, and sharing of these medications. 41 The FDA published a drug safety communication in May of 2023 updating warnings to improve the safe use of stimulants in the management of ADHD and other conditions. The FDA is requiring updates to the boxed warnings and prominent wording across this medication class. Health care professionals are urged to assess a patient’s risk of misuse, abuse, and addiction before prescribing stimulant medications and throughout therapy. Refill requests should also be evaluated for appropriate timing. It is important to counsel patients to take their medication as prescribed, not to share their medications with others, how to properly store and dispose of unused medication, and on signs and symptoms of non-medical use, addiction, and drug diversion. Signs and symptoms of stimulant overdose should also be reviewed with the patient and caregivers including when to seek emergency care.

Methylphenidate Formulations. Methylphenidate-based stimulants represent a common starting point for the medication management of ADHD in younger children. The AAP recommends it for preschool children after behavioral therapy. 7 The NICE recommends starting with this class of stimulants when ADHD symptoms persist after environmental modifications in children and young people. 12 Methylphenidate products are listed in Table 2 . 20 – 29 US Food and Drug Administration approval for each product varies per age. Medication formulations range from immediate release (3- to 5-hour duration of action) to extended release (8- to 13-hour duration of action). Brand name products fall into the methylphenidate, dexmethylphenidate, and serdexmethylphenidate categories. Product formul­ations include tablets, capsules, chewable tablets, orally dissolving tablets, solutions, suspensions, and a transdermal patch. Generic product options are available for several agents in this class, representing more cost-effective options. Patient education regarding unique dosage forms is imperative. For example, Concerta has an osmotic-controlled release methylphenidate tablet shell that allows for a slow, controlled release. 42 Yet, the tablet shell does not dissolve completely and may be seen intact in the stool. Additionally, the tablet does not change shape and thus, should not be used in patients with preexisting severe gastrointestinal narrowing. 24 Another important note is that most products are not interchangeable due to pharmacokinetic properties and dosage formulations and require a taper off/on when a shift of agents is necessary. Lastly, it is important to verify therapeutic equivalence with the FDA Orange Book for generic stimulant products.

A published pharmacological review has detailed characteristics of earlier products available for ADHD treatment. 42 Since 2018, at least 3 new medications have joined the methylphenidate class. These new dosage forms seek to increase the functionality of the class. They include a first-in-class prodrug formulation, another multilayer beaded long-acting formulation, and a distinctive delayed-release/extended-release product design. All 3 are capsules with a long duration of action allowing for once-daily dosing.

Approved in March 2021, Azstarys capsules contain dexmethylphenidate and serdexmethylphenidate in a fixed molar ratio of 30%/70%, respectively. 21 , 29 The prodrug component, serdexmethylphenidate, undergoes bioactivation in the lower GI tract. The unique formulation allows for continuous conversion to dexmethylphenidate providing extended concentrations (up to 13 hours) of active drug throughout the course of therapy. The capsules are offered in 3 distinctive strengths. The medication can be taken with or without food and is FDA-approved for patients ≥6 years of age. Capsules can be consumed whole, opened onto applesauce, or mixed with 50 mL water. Opened capsules must be taken within 10 minutes of mixing. Due to its prolonged duration of action, Azstarys is given once daily in the morning. Adverse effects are like other products in the class, with the most common being insomnia and suppressed appetite.

Adhansia XR was FDA-approved in February 2019, yet was discontinued by the manufacturer in July 2022. 21 , 27 Per the manufacturer, the product discontinuation was a business decision and not based on efficacy or safety concerns. 43 Authorized for patients ≥ 6 years, the product represented another encapsulated beaded long-acting methylphenidate formulation. 27 The significant advantage for Adhansia XR was its lengthy duration of action (roughly 16 hours). This formulation represented the longest interval product in the methylphenidate class.

Jornay PM represents a new methylphenidate formulation, a delayed-release/extended-release capsule. 28 Approved by the FDA in August 2018, Jornay PM is recommended for patients ≥6 years of age. 21 The product is manufactured in 5 unique strengths ranging from 20 to 100 mg. 28 Like other ADHD medications, capsules may be opened for administration, without crushing or chewing the capsule contents. Of importance, transitioning between Jornay PM and other methylphenidate products is not on a milligram-to-milligram exchange based on formulation and release mechanism differences. Jornay PM is unique in that it is taken in the evening, representing the first and only product in the stimulant class with this specific time of administration. Timing of the evening dose (6:30 to 9:30 pm) is recommended to optimize the efficacy and tolerability of the medication for the subsequent day. In children 6 to 12 years of age, 8 pm was found to be the optimal timing of administration. Pharmacokinetic properties of Jornay PM show that ≤5% of the total drug dose is released within the first 10 hours after dosing. Following this time, methylphenidate absorption occurs with a single peak and a median maximum concentration time of 14 hours. Jornay PM is marketed to improve the morning routine in patients with ADHD and subsequently to continue control for the dosing duration. Another potential benefit of this product is to assist patients who struggle with morning medication adherence. Due to its long duration, insomnia is the most common adverse effect (33%–41%) of this product in pediatric patients. 28

Amphetamine Formulations. Amphetamine-based stimulants represent a preferred ADHD treatment option for children, adolescents, and adults. NICE recommends this class as a second-line agent in children, behind methylphenidate. 12 In contrast, the AAP does not differentiate among stimulant classes, thus including amphetamine formations as a first-line option. 7 Comparing the two stimulant classes, amphetamines are associated with greater adverse effects and adverse events. 17 Amphetamine products are listed in Table 3 . 20 – 22 , 30 – 39 Medication formulations range from immediate release (4- to 5-hour duration of action) to extended release (8- to 16-hour duration of action). Brand name products fall into the mixed amphetamine salts, amphetamine, dextroamphetamine, and lisdexamfetamine categories. Product formulations include tablets, capsules, chewable tablets, orally disintegrating tablets, solutions, suspensions, and a newly approved transdermal patch. Generic product options are available for several agents in this class, once again representing more cost-effective options.

Xelstrym (dextroamphetamine) was FDA-approved in March 2022. 37 Indicated for patients ≥ 6 years, this product represents the only transdermal amphetamine patch formulation. Xelstrym was studied in children < 6 years, yet long-term weight loss was an ­undesirable adverse event. The patch formulation is available in 4 strengths (4.5 mg/9 hr, 9 mg/9 hr, 13.5 mg/9 hr, and 18 mg/9 hr). Xelstrym must be applied 2 hours before the anticipated effect is necessary and subsequently removed within 9 hours. Patch site rotation is also imperative. The external application of heat will increase drug absorption, and counseling needs to be provided to avoid heat usage. Xelstrym should not be exchanged for other amphetamine formulations based on dosing. Decreased appetite, headache, insomnia, and abdominal pain are a few adverse effects found with Xelstrym treatment.

In September 2017, Adzenys ER extended-release amphetamine suspension was FDA-approved for patients ≥6 years with ADHD. 34 The suspension contains a mixture of 50%/50% uncoated immediate-release microparticles to film-coated microparticles that delays the absorption of amphetamine. Unlike other stimulant preparations, Adzenys has published equivalent conversion doses to and/or from Adderall XR (mixed amphetamine salts). For illustration, an Adderall XR dose of 20 mg would be analogous with an Adzenys ER suspension dose of 12.5 mg based on medication pharmacokinetic properties. The Adzenys ER suspension is distributed in a 1.25-mg/mL concentration and holds a duration of action of approximately 10 to 12 hours. A key advantage of Adzenys ER is the suspension delivery formulation, which allows for ease of administration in patients unable to swallow a tablet or capsule.

Mydayis, as mixed amphetamine salts, was FDA-approved in June 2017. 33 This long-acting formulation includes 3 forms of drug-releasing beads, an immediate-release and 2 separate delayed-release beads that represent a 3:1 ratio of d -amphetamine and l -amphetamine. Like other capsule preparations, the contents can be mixed in applesauce for delivery, taking caution to not crush or chew. Mydayis is authorized for adolescents (≥13 years of age) and adults only. In studies with children <13 years at comparable doses, elevated plasma levels were found that equated to higher rates of insomnia and decreased appetite. Mydayis is formulated in 4 dosage concentrations. Due to the long duration of action (up to 16 hours), early morning medication administration is imperative. When contrasted with other mixed amphetamine salts formulations, a single dose of Mydayis 37.5 mg supplied similar plasma concentration profiles to the blend of a 25-mg mixed amphetamine salts extended-release capsule followed by a 12.5-mg immediate release dosage form 8 hours after. Mydayis extended-release capsules are the lengthiest duration amphetamine-based formulation on the market and have a longer duration than any currently available methylphenidate product.

Non-stimulants. There are 4 non-stimulant medications, 2 unique drug classes, with FDA approval for the management of ADHD ( Table 6 ). 20 – 22 , 44 – 46 The AAP guidelines include both classes in their treatment recommendations for both children 6 to 11 years and adolescents 12 to 17 years of age. 7 Additionally, NICE includes the use of the non-stimulants as treatment options for pediatric patients ≥ 5 years and adults. 12 The non-stimulant agents are recommended in patients whose symptoms do not respond to either stimulant compound or in situations of concern regarding abuse or diversion with the stimulant class. 7

Non-stimulant Treatment Options 20 – 22 , 44 – 46

ER, extended release

Norepinephrine Reuptake Inhibitors. Atomoxetine and viloxazine selectively inhibit norepinephrine transporters, thus increasing extracellular synaptic concentrations of norepinephrine and dopamine in the ­prefrontal cortex. 18 , 21 , 22 Unlike the stimulant class, these agents take approximately 1 to 2 weeks to see an initial benefit with 4 to 6 weeks to see the maximal effect on core ADHD symptoms. Atomoxetine is manufactured as a capsule in 7 strengths, available in ­generic form, and is dosed once daily. 45 Similarly, viloxazine is delivered once daily in a capsule formulation. 46 Both agents hold a boxed warning for suicidal ideation in children and adolescents and use within 14 days of a monoamine oxidase inhibitor is contraindicated. Atomoxetine is metabolized by CYP2D6. 45 Patients who are poor metabolizers of CYP2D6 may have a 5-fold increase in peak plasma concentrations, 10-fold higher area under the curve, and half-life of 24 hours, thus slower elimination of the drug. While atomoxetine is not a CYP2D6 inducer or inhibitor, dose adjustments may be warranted in extensive and poor metabolizer when administered with CYP2D6 inhibitors. Blood pressure and heart rate should also be monitored in patients taking atomoxetine and antihypertensives and pressor agents or systemic albuterol due to cardiovascular effects. Viloxazine is a strong inhibitor of CYP1A2 and weak inhibitor of CYP2D6, and CYP3A4. 46 Sensitive CYP1A2 substrates and CYP1A2 substrates with a narrow therapeutic index are contraindicated with viloxazine use, and moderately sensitive CYP1A2 substrates are not recommended for coadministration. Patients who are poor CYP2D6 metabolizers have higher peak concentrations and area under the curve of viloxazine compared with extensive metabolizers. Pharmacogenomic testing of patients may be considered prior to use of this medication class.

Alpha-2 Agonists. Guanfacine and clonidine extended-release formulations have FDA approval for the management of ADHD in children and adolescents as either monotherapy or in combination with another FDA-approved medication class. 18 , 21 , 22 The immediate-release formulations of guanfacine and clonidine may also be used off-label. These agents work by stimulating postsynaptic alpha-2-adrenergic receptors. The extended-release agents are both in tablet formulation, available in generic formulation, and are dosed once daily in the morning. Both agents hold warnings for hypotension, bradycardia, syncope, sedation, somnolence, and dry mouth. It is also ­important to educate the patient/caregiver that these agents should not be stopped abruptly to the risk of rebound hypertension. If a patient encounters repeated orthostasis or fainting, a reduction in dose or therapy change is warranted. As with the norepinephrine reuptake inhibitors, clinical response may be delayed with a maximal effect seen at 2 to 4 weeks of therapy.

Off-Label Pharmacologic Treatment Options

Off-label treatment options for the management of ADHD in children have been studied. One agent investigated in both children and adults is bupropion. It holds a parallel mechanism of action and is structurally similar to the stimulant class. 47 However, the medication is contraindicated in patients with a seizure disorder or in patients with a coexisting condition that may put them at risk for seizures (e.g., bulimia nervosa ). 21 , 22 Bupropion also carries the antidepressant-class warning of suicidal ideation in children and adolescents. Another agent studied off-label for ADHD is modafinil. The current labeled use for modafinil is excessive daytime sleepiness related to narcolepsy, obstructive sleep apnea, or shift work sleep disorder. 22 The exact mechanism of modafinil is unclear, but it maintains links to dopamine similar to amphetamine. A network meta-analysis looked at the efficacy and tolerability of various medications for children, adolescents, and adults with ADHD. 17 Both bupropion and modafinil were found to be more efficacious than placebo. Yet the authors note a large confidence interval in relation to the efficacy and tolerability of both agents and recommend caution with interpreting the data. In the end, more information is needed with these agents in the treatment of pediatric ADHD.

ADHD is a common disease practitioners encounter in the pediatric population. Behavioral therapy and/or stimulant medication remain the first-line treatment recommendations. Stimulant products differ based on pharmacokinetic profile and dosage formulation. Additionally, new stimulant products as well as non-stimulants continue to receive approval for use in the pediatric population and drug shortages can impact prescribing. Pharmacists can educate other health care providers on the similarities and differences of ADHD medication to improve the efficacy and safety of therapy for the patient.

ABBREVIATIONS

Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria.