Clinical trials landscape¶
TL;DR — The ADHD trial landscape spans established drugs, novel nonstimulants, behavioral programs, sleep interventions, digital therapeutics and neuromodulation. Acute symptom trials remain far more common than long-term functional trials. Live ClinicalTrials.gov retrieval shows active work in early intervention (NCT04627415), CBT (NCT06604845), metacognitive treatment (NCT07162831), accelerated iTBS (NCT07219810), pediatric clonidine ER (NCT07044609) and long-term youth trajectories (NCT06978452). Registry status is administrative, not evidence of benefit.
Live registry snapshot¶
| NCT | Intervention/question | Status retrieved 2026-08-30 | Design note |
|---|---|---|---|
| NCT04627415 | Project PEAK early intervention | Recruiting | Non-drug early intervention |
| NCT07162831 | Metacognitive intervention | Recruiting | Children/adolescents |
| NCT06604845 | Group CBT versus structured activity | Enrolling by invitation | Adult active comparator |
| NCT07219810 | Accelerated iTBS targets | Recruiting | Adolescent neuromodulation |
| NCT06946433 | tDCS in adults with ASD and/or ADHD | Completed | Transdiagnostic sample |
| NCT07044609 | Clonidine ER in ADHD with ODD | Not yet recruiting | Phase 4 |
| NCT04219280 | ADHD treatment in Down syndrome | Active, not recruiting | Phase 4 |
| NCT06978452 | Long-term youth trajectories | Recruiting | Observational/optimization |
| NCT07665658 | Supplements and inflammatory markers | Recruiting | Biomarker-linked intervention |
| NCT05802680 | Near-infrared stimulation | Recruiting | Neurocognitive intervention |
What the published trial network establishes¶
The medication network contains 133 double-blind RCTs and supports short-term efficacy across several agents, with age-specific differences in the efficacy–tolerability balance (Cortese 2018, PMID 30097390). This mature acute network contrasts with limited long-term functional randomization.
Digital proof of concept is exemplified by STARS-ADHD: 348 randomized children and a positive objective attention endpoint over four weeks (Kollins 2020, PMID 33334505; NCT02674633). Transfer to real-world function and durability remain separate hypotheses.
Design pathologies to track¶
Short follow-up, enriched samples, unblinded ratings, weak comparators, multiple outcomes, treatment-experienced participants and sponsor-controlled analysis can all inflate apparent transportability. Trials should report function, quality of life, adverse effects and discontinuation alongside symptoms.
Personalization¶
Pharmacogenomic and neuroimaging prediction studies remain exploratory. A valid personalization trial must prospectively assign treatment using the marker and show better outcomes than ordinary care—not merely correlate baseline features with response.
How to read the evidence¶
- Diagnostic case–control separation is not the same as accuracy among referred patients.
- Symptom change is not interchangeable with functional improvement.
- Short randomized trials estimate acute efficacy, not decades-long benefit or harm.
- Observational within-person and target-trial designs reduce some confounding but remain nonrandomized.
- Parent, teacher, clinician, self-report and objective tasks measure different vantage points.
- Statistical significance does not establish a patient-important effect.
- Population averages should not be converted into deterministic individual predictions.
- Absence of evidence in a subgroup is not evidence of identical effects.
Minimum standards for the next evidence generation¶
- Prespecify one primary outcome and its clinically important threshold.
- Report symptoms, function, quality of life and harms separately.
- Use clinically relevant comparators rather than only healthy controls.
- Retain and report participants who discontinue treatment.
- Test generalization across sex, age, ancestry, comorbidity and setting.
- Separate model development, internal validation and external validation.
- Declare medication exposure, concomitant care and rater blinding.
- Make null and contradictory results visible rather than averaging away design differences.
Recurring evidence gaps¶
- Females, older adults and people with complex comorbidity remain underrepresented.
- Functional outcomes are measured less consistently than core symptoms.
- Follow-up usually ends before major educational or occupational transitions.
- Comparator choice often makes effects look more or less specific than they are.
- Treatment discontinuation and switching weaken long-term causal contrasts.
- Independent replication is uncommon for biomarkers and digital interventions.
Retrieved evidence map¶
The following records were retrieved through this page’s six live PubMed searches. Inclusion here means the record is directly relevant to the page’s scope; it does not imply equal quality or endorsement of its conclusions.
| Citation | Indexed study lens | Directly studied question/title | Interpretation boundary |
|---|---|---|---|
| Cortese 2018, PMID 30097390 | Comparative Study, Journal Article | Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. | Interpret within its sampled population and comparator |
| Kollins 2020, PMID 33334505 | Journal Article, Randomized Controlled Trial | A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. | Interpret within its sampled population and comparator |
| Faraone 2019, PMID 29892054 | Journal Article, Research Support, Non-U.S. Gov't | Genetics of attention deficit hyperactivity disorder. | Interpret within its sampled population and comparator |
| Zhao 2024, PMID 38728075 | Journal Article, Randomized Controlled Trial | A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial. | Interpret within its sampled population and comparator |
| Dakwar-Kawar 2023, PMID 37528107 | Randomized Controlled Trial, Journal Article | Transcranial random noise stimulation combined with cognitive training for treating ADHD: a randomized, sham-controlled clinical trial. | Interpret within its sampled population and comparator |
| Sullivan 2024, PMID 39173523 | Journal Article, Randomized Controlled Trial | A randomized clinical trial to evaluate feasibility, tolerability, and preliminary target engagement for a novel executive working memory training in adolescents with ADHD. | Interpret within its sampled population and comparator |
| Chen 2025, PMID 39591718 | Journal Article, Randomized Controlled Trial | Prediction of methylphenidate treatment response for ADHD using conventional and radiomics T1 and DTI features: Secondary analysis of a randomized clinical trial. | Interpret within its sampled population and comparator |
| Bergmann 2026, PMID 42142506 | Journal Article, Randomized Controlled Trial | Effects of a novel individualized digital cognitive training on ADHD characteristics, quality of life, and cognitive functioning in adults with ADHD: A randomized controlled trial. | Interpret within its sampled population and comparator |
| Lam 2022, PMID 36349428 | Randomized Controlled Trial, Journal Article | Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD. | Interpret within its sampled population and comparator |
| Clark 2008, PMID 18198165 | Journal Article, Randomized Controlled Trial | Vestibular Stimulation for ADHD: randomized controlled trial of Comprehensive Motion Apparatus. | Interpret within its sampled population and comparator |
| Morgan 2022, PMID 32930610 | Journal Article, Randomized Controlled Trial | Co-Occurring Psychopathology Moderates Social Skills Improvement in a Randomized Controlled Trial of a Collaborative School-Home Intervention for Children with ADHD. | Interpret within its sampled population and comparator |
| Ghannadi 2025, PMID 41604557 | Journal Article, Randomized Controlled Trial | Sulforaphane Adjunct to Methylphenidate for Attention-deficit/Hyperactivity Disorder: A Randomized, Double-blind, Placebo-controlled Trial. | Interpret within its sampled population and comparator |
| Nourredine 2026, PMID 42134365 | Journal Article, Systematic Review | Pharmacological interventions for ADHD: a systematic review and dose-effect network meta-analysis. | Interpret within its sampled population and comparator |
| Dang 2025, PMID 40598377 | Journal Article, Multicenter Study | The promoting effects of digital targeted cognitive training in medication treatment for children with ADHD: a randomized controlled trial. | Interpret within its sampled population and comparator |
| Flannery 2024, PMID 38685016 | Journal Article, Randomized Controlled Trial | Secondary analyses of sex differences in attention improvements across three clinical trials of a digital therapeutic in children, adolescents, and adults with ADHD. | Interpret within its sampled population and comparator |
| Oh 2024, PMID 36862162 | Meta-Analysis, Systematic Review | Effects of game-based digital therapeutics on attention deficit hyperactivity disorder in children and adolescents as assessed by parents or teachers: a systematic review and meta-analysis. | Interpret within its sampled population and comparator |
| Stamatis 2024, PMID 39128918 | Journal Article, Multicenter Study | Real-time cognitive performance metrics derived from a digital therapeutic for inattention predict ADHD-related clinical outcomes: Replication across three independent trials of AKL-T01. | Interpret within its sampled population and comparator |
| D'Amelio 2026, PMID 41810578 | Journal Article, Randomized Controlled Trial | Effectiveness of attexis, a digital intervention based on cognitive behavioral therapy for adults with ADHD: a randomized controlled trial. | Interpret within its sampled population and comparator |
| Leffa 2022, PMID 35921102 | Journal Article, Randomized Controlled Trial | Transcranial Direct Current Stimulation vs Sham for the Treatment of Inattention in Adults With Attention-Deficit/Hyperactivity Disorder: The TUNED Randomized Clinical Trial. | Interpret within its sampled population and comparator |
| Fu 2025, PMID 39829146 | Journal Article, Meta-Analysis | Efficacy and Safety of Transcranial Magnetic Stimulation for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis. | Interpret within its sampled population and comparator |
| Chen 2026, PMID 40701403 | Journal Article, Systematic Review | Noninvasive Brain Stimulation in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Treatment Efficacy and Targeting Strategies. | Interpret within its sampled population and comparator |
| Zhang 2026, PMID 41610600 | Journal Article, Systematic Review | A systematic review of transcranial direct current stimulation (tDCS) for adults with attention deficit/hyperactivity disorder (ADHD). | Interpret within its sampled population and comparator |
| Fu 2026, PMID 41420112 | Journal Article, Randomized Controlled Trial | Efficacy and safety of transcranial alternating current stimulation in adults with attention deficit hyperactivity disorder: a double-blind randomized sham-controlled trial. | Interpret within its sampled population and comparator |
| Neurofeedback Collaborative Group 2023, PMID 36521694 | Randomized Controlled Trial, Journal Article | Neurofeedback for Attention-Deficit/Hyperactivity Disorder: 25-Month Follow-up of Double-Blind Randomized Controlled Trial. | Interpret within its sampled population and comparator |
| Guimarães 2021, PMID 33663047 | Clinical Trial Protocol, Journal Article | The effects of transcranial direct current stimulation on attention and inhibitory control of children and adolescents with attention-deficit/hyperactivity disorder (ADHD): Study protocol for a randomized, sham-controlled, triple-blind, cross-over trial. | Interpret within its sampled population and comparator |
| Schneider 2025, PMID 40524600 | Journal Article, Randomized Controlled Trial | Enhancing Goal Achievement in Adults With ADHD: A Participant-Centered Evaluation of Transcranial Direct Current Stimulation From the TUNED Trial. | Interpret within its sampled population and comparator |
| Lukito 2024, PMID 39428885 | Journal Article, Randomized Controlled Trial | Effects of fMRI neurofeedback of right inferior frontal cortex on inhibitory brain activation in children with ADHD. | Interpret within its sampled population and comparator |
| McGough 2005, PMID 15950009 | Journal Article, Research Support, N.I.H., Extramural | Attention-deficit/hyperactivity disorder pharmacogenomics. | Interpret within its sampled population and comparator |
| Kieling 2010, PMID 20235795 | Journal Article, Review | A current update on ADHD pharmacogenomics. | Interpret within its sampled population and comparator |
| Stein 2008, PMID 18295157 | Journal Article, Research Support, N.I.H., Extramural | The pharmacogenomic era: promise for personalizing attention deficit hyperactivity disorder therapy. | Interpret within its sampled population and comparator |
| Kambeitz 2014, PMID 23588108 | Journal Article, Meta-Analysis | Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD. | Interpret within its sampled population and comparator |
| Yuan 2021, PMID 34797323 | Journal Article, Meta-Analysis | Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis. | Interpret within its sampled population and comparator |
Open questions¶
- Which active trials include durable functional primary outcomes? (Cortese 2018, PMID 30097390)
- Can neuromodulation effects replicate across targets and sham procedures? (NCT07219810)
- Will marker-guided treatment outperform careful titration without a marker? (Faraone 2019, PMID 29892054)
Related pages¶
- Pharmacologic treatment — connected evidence domain.
- Psychosocial and digital treatment — connected evidence domain.
- Biomarkers — connected evidence domain.
- Long-term outcomes and quality of life — connected evidence domain.
- Guidelines — connected evidence domain.
References¶
- Cortese et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The lancet. Psychiatry. 2018;5:727-738. PMID 30097390
- Kollins et al. A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. The Lancet. Digital health. 2020;2:e168-e178. PMID 33334505
- Faraone et al. Genetics of attention deficit hyperactivity disorder. Molecular psychiatry. 2019;24:562-575. PMID 29892054
- Zhao et al. A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial. Journal of medical Internet research. 2024;26:e55569. PMID 38728075
- Dakwar-Kawar et al. Transcranial random noise stimulation combined with cognitive training for treating ADHD: a randomized, sham-controlled clinical trial. Translational psychiatry. 2023;13:271. PMID 37528107
- Sullivan et al. A randomized clinical trial to evaluate feasibility, tolerability, and preliminary target engagement for a novel executive working memory training in adolescents with ADHD. Behaviour research and therapy. 2024;181:104615. PMID 39173523
- Chen et al. Prediction of methylphenidate treatment response for ADHD using conventional and radiomics T1 and DTI features: Secondary analysis of a randomized clinical trial. NeuroImage. Clinical. 2025;45:103707. PMID 39591718
- Bergmann et al. Effects of a novel individualized digital cognitive training on ADHD characteristics, quality of life, and cognitive functioning in adults with ADHD: A randomized controlled trial. Journal of psychiatric research. 2026;200:26-37. PMID 42142506
- Lam et al. Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD. The American journal of psychiatry. 2022;179:947-958. PMID 36349428
- Clark et al. Vestibular Stimulation for ADHD: randomized controlled trial of Comprehensive Motion Apparatus. Journal of attention disorders. 2008;11:599-611. PMID 18198165
- Morgan et al. Co-Occurring Psychopathology Moderates Social Skills Improvement in a Randomized Controlled Trial of a Collaborative School-Home Intervention for Children with ADHD. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. 2022;51:543-555. PMID 32930610
- Ghannadi et al. Sulforaphane Adjunct to Methylphenidate for Attention-deficit/Hyperactivity Disorder: A Randomized, Double-blind, Placebo-controlled Trial. Clinical neuropharmacology. 2025;48:181-187. PMID 41604557
- Nourredine et al. Pharmacological interventions for ADHD: a systematic review and dose-effect network meta-analysis. The lancet. Psychiatry. 2026;13:485-495. PMID 42134365
- Dang et al. The promoting effects of digital targeted cognitive training in medication treatment for children with ADHD: a randomized controlled trial. BMC medicine. 2025;23:371. PMID 40598377
- Flannery et al. Secondary analyses of sex differences in attention improvements across three clinical trials of a digital therapeutic in children, adolescents, and adults with ADHD. BMC public health. 2024;24:1195. PMID 38685016
- Oh et al. Effects of game-based digital therapeutics on attention deficit hyperactivity disorder in children and adolescents as assessed by parents or teachers: a systematic review and meta-analysis. European child & adolescent psychiatry. 2024;33:481-493. PMID 36862162
- Stamatis et al. Real-time cognitive performance metrics derived from a digital therapeutic for inattention predict ADHD-related clinical outcomes: Replication across three independent trials of AKL-T01. Translational psychiatry. 2024;14:328. PMID 39128918
- D'Amelio et al. Effectiveness of attexis, a digital intervention based on cognitive behavioral therapy for adults with ADHD: a randomized controlled trial. Psychological medicine. 2026;56:e54. PMID 41810578
- Leffa et al. Transcranial Direct Current Stimulation vs Sham for the Treatment of Inattention in Adults With Attention-Deficit/Hyperactivity Disorder: The TUNED Randomized Clinical Trial. JAMA psychiatry. 2022;79:847-856. PMID 35921102
- Fu et al. Efficacy and Safety of Transcranial Magnetic Stimulation for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis. Brain and behavior. 2025;15:e70246. PMID 39829146
- Chen et al. Noninvasive Brain Stimulation in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Treatment Efficacy and Targeting Strategies. Journal of the American Academy of Child and Adolescent Psychiatry. 2026;65:369-391. PMID 40701403
- Zhang et al. A systematic review of transcranial direct current stimulation (tDCS) for adults with attention deficit/hyperactivity disorder (ADHD). Journal of psychiatric research. 2026;195:74-84. PMID 41610600
- Fu et al. Efficacy and safety of transcranial alternating current stimulation in adults with attention deficit hyperactivity disorder: a double-blind randomized sham-controlled trial. Molecular psychiatry. 2026;31:2675-2684. PMID 41420112
- Neurofeedback Collaborative Group. Neurofeedback for Attention-Deficit/Hyperactivity Disorder: 25-Month Follow-up of Double-Blind Randomized Controlled Trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2023;62:435-446. PMID 36521694
- Guimarães et al. The effects of transcranial direct current stimulation on attention and inhibitory control of children and adolescents with attention-deficit/hyperactivity disorder (ADHD): Study protocol for a randomized, sham-controlled, triple-blind, cross-over trial. Medicine. 2021;100:e24283. PMID 33663047
- Schneider et al. Enhancing Goal Achievement in Adults With ADHD: A Participant-Centered Evaluation of Transcranial Direct Current Stimulation From the TUNED Trial. Journal of attention disorders. 2025;29:1070-1078. PMID 40524600
- Lukito et al. Effects of fMRI neurofeedback of right inferior frontal cortex on inhibitory brain activation in children with ADHD. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2024;379:20230097. PMID 39428885
- McGough. Attention-deficit/hyperactivity disorder pharmacogenomics. Biological psychiatry. 2005;57:1367-73. PMID 15950009
- Kieling et al. A current update on ADHD pharmacogenomics. Pharmacogenomics. 2010;11:407-19. PMID 20235795
- Stein et al. The pharmacogenomic era: promise for personalizing attention deficit hyperactivity disorder therapy. Child and adolescent psychiatric clinics of North America. 2008;17:475-90, xi-xii. PMID 18295157
- Kambeitz et al. Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD. The pharmacogenomics journal. 2014;14:77-84. PMID 23588108
- Yuan et al. Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis. Medicine. 2021;100:e27858. PMID 34797323