Diagnosis:
- Multiple approaches showed promising diagnostic performance (e.g., using parental rating scales), but estimates of performance varied considerably across studies, and the strength of evidence (SoE)was generally low.
- Diagnostic test performance likely depends on whether youth with attention deficit hyperactivity disorder (ADHD) are being differentiated from typically developing children or from clinically referred children who had some kind of mental health or behavioral problem.
- Rating scales for parent, teacher, or self-assessment as a diagnostic tool for ADHD have high internal consistency but poor to moderate reliability between raters, indicating that obtaining ratings from multiple informants (the youth, both parents, and teachers) may be valuable to inform clinical judgement.
- Studies evaluating neuropsychological tests of executive functioning (e.g., Continuous Performance Test) used study-specific combinations of individual cognitive measures, making it difficult to compare performance across studies.
- Diagnostic performance of biomarkers, EEG, and MRI scans show great variability across studies and their ability to aid clinical diagnosis for ADHD remains unclear. Studies have rarely assessed test-retest reliability, no findings have been replicated prospectively using the same measure in independent samples, and real-world effectiveness studies of diagnostic performance have not been conducted.
- Very few studies have assessed performance of diagnostic tools for ADHD in children under the age of seven years and more research is needed.
- The identified diagnostic studies did not assess the adverse effects of being labeled correctly or incorrectly as having a diagnosis of ADHD.
Treatment:
- We found that several treatment modalities improve core ADHD symptoms compared to control groups (e.g., placebo). These include FDA-approved medications and psychosocial interventions with high or moderate strength of evidence.
- FDA-approved stimulant (e.g., methylphenidate, amphetamine) and non-stimulant (e.g., atomoxetine, alpha agonist) medications had the strongest evidence across interventions for significantly improving ADHD symptoms and additional outcomes, including broadband measures and functional impairment.
- Head-to-head comparisons did not detect statistically significant differences between stimulant and non-stimulant medications for most effectiveness outcomes and adverse events.
- We found little evidence that combination therapies of medication plus psychosocial therapies produce better results than medication alone, but existing research evaluated unique combinations of intervention components.
- Despite the large body of research, comparative effectiveness and safety information is limited and more research is needed to help choose between treatments.
- Data were insufficient to assess the effect of co-occurring disorders on treatment effects.
- We found too few studies reporting on diversion to quantify the risk of diversion of pharmacological treatment.
Monitoring:
- Very few monitoring studies have been reported, and more research is needed on how youth with ADHD should be monitored over time.
- Different assessment modalities may provide valid but different perspectives, and more than a single assessment modality may be required for comprehensive and effective monitoring of ADHD outcomes over time.
Objective. The systematic review assessed evidence on the diagnosis, treatment, and monitoring of attention deficit hyperactivity disorder (ADHD) in children and adolescents to inform a planned update of the American Academy of Pediatrics (AAP) guidelines.
Data sources. We searched PubMed®, Embase®, PsycINFO®, ERIC, clinicaltrials.gov, and prior reviews for primary studies published since 1980. The report includes studies published to June 15, 2023.
Review methods. The review followed a detailed protocol and was supported by a Technical Expert Panel. Citation screening was facilitated by machine learning; two independent reviewers screened full text citations for eligibility. We abstracted data using software designed for systematic reviews. Risk of bias assessments focused on key sources of bias for diagnostic and intervention studies. We conducted strength of evidence (SoE) and applicability assessments for key outcomes. The protocol for the review has been registered in PROSPERO (CRD42022312656).
Results. Searches identified 23,139 citations, and 7,534 were obtained as full text. We included 550 studies reported in 1,097 publications (231 studies addressed diagnosis, 312 studies addressed treatment, and 10 studies addressed monitoring). Diagnostic studies reported on the diagnostic performance of numerous parental ratings, teacher rating scales, teen/child self-reports, clinician tools, neuropsychological tests, EEG approaches, imaging, and biomarkers. Multiple approaches showed promising diagnostic performance (e.g., using parental rating scales), although estimates of performance varied considerably across studies and the SoE was generally low. Few studies reported estimates for children under the age of 7. Treatment studies evaluated combined pharmacological and behavior approaches, medication approved by the Food and Drug Administration, other pharmacologic treatment, psychological/behavioral approaches, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, school interventions, and provider or model-of-care interventions. Medication treatment was associated with improved broadband scale scores and ADHD symptoms (high SoE) as well as function (moderate SoE), but also appetite suppression and adverse events (high SoE). Psychosocial interventions also showed improvement in ADHD symptoms based on moderate SoE. Few studies have evaluated combinations of pharmacological and youth-directed psychosocial interventions, and we did not find combinations that were systematically superior to monotherapy (low SoE). Published monitoring approaches for ADHD were limited and the SoE is insufficient.
Conclusion. Many diagnostic tools are available to aid the diagnosis of ADHD, but few monitoring strategies have been studied. Medication therapies remain important treatment options, although with a risk of side effects, as the evidence base for psychosocial therapies strengthens and other nondrug treatment approaches emerge.
Findings
Questions
Future Research
Our searches identified 23,116 citations. Of these, we obtained 7,507 as full text. In total, 548 studies reported in 1,092 publications met the eligibility criteria. This included 230 studies addressing diagnosis (KQ1), 311 studies addressing treatment (KQ2), and 10 studies addressing monitoring (KQ3). The risk of bias in included studies varied considerably. The median minimum age in included studies was six years old and the median number of girls included in the studies was 25 percent.
Treatment studies evaluated FDA-approved pharmacologic treatment and other pharmaceutical agents, psychological or behavioral approaches, combined pharmacological and behavior, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, school interventions, and provider or model of care interventions aiming to treat or manage ADHD.
Multiple approaches showed promising diagnostic performance (e.g., using parental rating scales), but estimates of performance varied considerably across studies, with a generally low SoE.
We found evidence that several treatments significantly improve ADHD symptoms, including medications, child-directed psychosocial therapies, parent support, and neurofeedback. Medications had the strongest evidence for improving ADHD symptoms and other outcomes, including disruptive behaviors and broadband scores. Effect sizes were larger for stimulants than non-stimulant medications compared to control, though head-to-head comparisons did not detect differences. For indirect comparisons, participants reporting adverse events were common with stimulants and norepinephrine reuptake inhibitors, but less common with the alpha-agonist guanfacine.
Very few monitoring studies have been reported, and more research is needed on how youth with ADHD should be monitored over time.
Despite the large body of research, comparative effectiveness and safety information is limited and more research is needed to help choose between treatments.
NOTE: The number of studies listed below includes all studies that met our inclusion criteria for the category; the number of studies shown in the Findings column indicates the number of studies that could be included in the meta-analysis.
Key Questions
Key Question 1. For the diagnosis of ADHD:
KQ 1a. What is the comparative diagnostic accuracy of approaches that can be used in the primary care practice setting or by specialists to diagnose ADHD among individuals younger than 7 years of age?
KQ 1b. What is the comparative diagnostic accuracy of EEG, imaging, or approaches assessing executive function that can be used in the primary care practice setting or by specialists to diagnose ADHD among individuals aged 7 through 17?
KQ 1c. For both populations, how does the comparative diagnostic accuracy of these approaches vary by clinical setting, including primary care or specialty clinic, or patient subgroup, including, age, sex, or other risk factors associated with ADHD?
KQ 1d. What are the adverse effects associated with being labeled correctly or incorrectly as having ADHD?
Key Question 2. What are the comparative safety and effectiveness of pharmacologic and/or nonpharmacologic treatments of ADHD in improving outcomes associated with ADHD?
KQ 2a. How do these outcomes vary by presentation (inattentive, hyperactive/impulsive, and combined) or other co-occurring conditions?
KQ 2b. What is the risk of diversion of pharmacologic treatment?
Key Question 3. What are the comparative safety and effectiveness of different empirical monitoring strategies to evaluate the effectiveness of treatment in improving ADHD symptoms or other long-term outcomes?
This review does not provide cost information.
Strengths and Limitations
A major strength of this review is its inclusiveness, incorporating publications from 1980 and yielding more than 500 separate studies that informed our findings. Other strengths include: a review of evidence for the utility of biomarkers, EEG, and neuroimaging measures in the diagnosis of ADHD; parsing of non-pharmacological therapies by the target of the therapy (the youth, parent, or school); and the parsing of ADHD outcome measures to provide more clarity on the functional domains that treatments affect.
Despite the large number of included studies, we restricted this review to studies that reported on children with a clinically confirmed diagnosis of ADHD, excluding studies with broader samples (such as evaluations of psychosocial programs that were not specific to youth with a clinical diagnosis). In addition, although studies of children of all ages were eligible for inclusion in the report, the number of studies exclusively addressing younger children with ADHD were relatively few. The median minimum age in included studies was six years old. Samples were predominantly male, and the median number of girls included in the studies was only 25 percent. Furthermore, smaller studies were not included unless they demonstrated a power analysis, which may have excluded studies of more intensive treatments. We also excluded studies documenting very short-term treatment effects by requiring studies to report on a minimum treatment duration of four weeks. This requirement may have excluded relevant brief interventions, or very intense psychosocial interventions delivered in a short time period. Furthermore, this synthesis was focused on outcomes selected with the help of an expert panel, and it should be noted that individual interventions may show effects on other outcomes. Because few studies compared treatment effects in direct, head-to-head comparisons, we had to explore modifiers indirectly, across studies. Finally, despite a very comprehensive search, few monitoring studies were available to inform this report.
Future Research
One of the most important potential uses of this systematic review would be the identification of effect modifiers for both the performance of diagnostic tools and therapeutic interventions – for example, determining whether a diagnostic tool performs better or worse, or a treatment is more or less effective, in one patient subgroup than another (KQ1c and KQ2a), such as in younger or older patients, in ethnic minorities, in those experiencing material hardship, in patients with a comorbid illness, or in those with a specific ADHD presentation. These analyses are essential for improving clinical assessments and treatment planning. Future studies of ADHD should more systematically address the modifier effects of these patient characteristics. More research is needed on the performance of diagnostic tools, the consequences of being misdiagnosed as either having or not having ADHD, the real-world effectiveness and long-term outcomes of medication and other therapies, and effectiveness of monitoring strategies. Much more research is needed on the diagnosis and treatment of preschool children who have ADHD.
Future Research on ADHD Diagnosis
Future studies of diagnostic tools should include assessment of how well the tools distinguish ADHD youth not simply from typically developing youth, but especially from youth who have other emotional and behavioral problems. They should also assess the potential adverse consequences of youth being incorrectly diagnosed with or without ADHD. Research is needed to identify consensus algorithms that combine rating scale data from multiple informants to improve the clinical diagnosis of ADHD, which at present is unguided, ad hoc, and suboptimal.
Despite the theoretical promise and a large number of prior studies of the use of continuous performance tests, EEG, or imaging to diagnose ADHD, conclusions about these potential diagnostic tools was severely limited by the use of different diagnostic measures within each test modality, differing diagnostic thresholds applied to those measures across studies, and differing algorithms that combine those variables to reach a diagnostic decision, and the frequent failure to clearly report those study elements in the publication. Therefore, to support future efforts at synthetic analyses, diagnostic studies should report sufficient detail of their measures and diagnostic algorithms—precise operational definitions and measurements of the variable(s) used for diagnosis, any diagnostic algorithm employed, the chosen statistical cut-offs, and the number of false positives and false negatives the diagnostic tool yields.
Studies of diagnostic tools should include ROC analyses to support comparison of test performance across studies that are independent of diagnostic threshold for the tool. Studies should also include assessment of test-retest reliability to help discern whether variability in measures and test performance across settings is a function of setting or is a consequence of measurement variability across time. Future studies should address the role of co-occurring disorders in the diagnostic process and their influences on their performance of the diagnostic tools. In addition, more studies are needed that compare the diagnostic accuracy of different test modalities head-to-head.
Making available in public repositories the raw, individual-level data, as well as the algorithms or computer code, for diagnostic tools is important to aid future efforts at replication, synthesis, and new discovery. Independent replication of performance measures of diagnostic tools in real-world settings is essential prior to FDA approval and before recommendations for widespread clinical use.
Finally, the "diagnostic tests” that are most often used clinically, usually at considerable financial expense, are neuropsychological measures of “executive functioning”. These include, among others, measures of working memory and errors of omission on continuous performance tests (thought to represent the clinical construct of inattention) and measures of impulsive responding on continuous performance tests (thought to represent the clinical construct of impulsivity). These and other objective, quantitative neuropsychological test measures of executive functioning notoriously correlate only weakly with the clinical constructs of inattention, impulsivity, and hyperactivity that are based on observation of real-world behavior and that define ADHD.177 Many youth with ADHD have normal executive functioning profiles on neuropsychological testing, and many who have impaired executive functioning on neuropsychological tests do not have ADHD. A major open question for future research is how these two constructs – neuropsychological test measures of executive functioning and the real-world functional problems that define ADHD—map on to one another, and how the correspondence of that mapping can be improved.
Future Research on ADHD Treatment
More trials are needed that compare alternative interventions head-to-head or that compare combination treatments with monotherapy. Future studies of psychosocial and parent interventions should employ study designs that support more valid causal inferences and higher strength of evidence for the effectiveness of the interventions assessed, including active attention comparator conditions and effective blinding of participants and assessors to study interventions and hypotheses. More and higher quality studies with independent replication are needed to assess the effectiveness of individual complementary and alternative therapies, as well as exercise. Much more research is needed to assess long-term treatment compliance, long-term treatment effectiveness across a wide array of interventions, patient-centered outcomes beyond ADHD symptom improvement, medication diversion, and adverse effects associated with treatment (including non-pharmacological interventions).
Studies evaluating ADHD interventions should address the role of patient characteristics as modifiers of treatment effects. This effort will help to identify which treatments are most effective for which patients, to aid in the development of personalized treatments for youth with ADHD. To aid discovery and confirmation of these modifiers, future treatment studies should make publicly available all individual-level demographic, clinical, comorbidity, treatment, and all available outcome data (not only the primary outcomes), together with a detailed data dictionary. Patient-centered outcomes that assess functional domains other than ADHD symptoms, such as functional impairment and academic performance, should be acquired in clinical trials and shared publicly.
Future Research on ADHD Monitoring
Much more research is needed that compares the utility of various strategies for monitoring outcomes and tracking response to treatment over time in ADHD youth. The temporal stability of outcome measures and their sensitivity to change in response to treatment should be assessed to support ADHD monitoring strategies.
Future synthetic studies should also consider reviewing studies of long-term outcomes in ADHD youth, even if not in the context of comparing monitoring strategies, as the findings will be of interest to patients, parents, and clinicians and will critically inform treatment decisions.
Applicability
Several included studies reported multiple exclusions for eligible participants, which limited the generalizability of findings. Diagnostic performance, as well as treatment effects in clinical practice, may not translate from the favorable effects shown in the documented research to real world practice. In addition, the number of girls included in the identified studies was small and several studies did not include any female participants, potentially limiting the applicability of the findings.
Peterson BS, Trampush J, Maglione M, et al. Treatments for ADHD in Children and Adolescents: A Systematic Review. Pediatrics. 2024 April;153(4): e2024065787. DOI: https://doi.org/10.1542/peds.2024-065787. PMID: 38523592.
Peterson BS, Trampush J, Brown M, et al. Tools for the Diagnosis of ADHD in Children and Adolescents: A Systematic Review. Pediatrics. 2024 April;153(4): e2024065854. DOI: https://doi.org/10.1542/peds.2024-065854. PMID: 38523599.
Peterson BS, Trampush J, Maglione M, Bolshakova M, Brown M, Rozelle M, Motala A, Yagyu S, Miles J, Pakdaman S, Gastelum M, Nguyen BT, Tokutomi E, Lee E, Belay JZ, Schaefer C, Coughlin B, Celosse K, Molakalapalli S, Shaw B, Sazmin T, Onyekwuluje AN, Tolentino D, Hempel S. ADHD Diagnosis and Treatment in Children and Adolescents. Comparative Effectiveness Review No. 267. (Prepared by the Southern California Evidence-based Practice Center under Contract No. 75Q80120D00009.) AHRQ Publication No. 24-EHC003. PCORI Publication No. 2023-SR-03. Rockville, MD: Agency for Healthcare Research and Quality; March 2024. DOI: https://doi.org/10.23970/AHRQEPCCER267. Posted final reports are located on the Effective Health Care Program search page.
