{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:51:09Z","timestamp":1778701869438,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This study was funded by Akili Interactive Labs, Boston, MA."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>STARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8\u201314-year-old children with attention-deficit\/hyperactivity disorder (ADHD) on stimulant medication (<jats:italic>n<\/jats:italic>\u2009=\u2009130) or not on any ADHD medication (<jats:italic>n<\/jats:italic>\u2009=\u200976). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale\u2014Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: \u22120.7, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; No Stimulants: \u22120.5, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01\u2019s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.<\/jats:p>","DOI":"10.1038\/s41746-021-00429-0","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T11:03:37Z","timestamp":1616756617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-6935","authenticated-orcid":false,"given":"Scott H.","family":"Kollins","sequence":"first","affiliation":[]},{"given":"Ann","family":"Childress","sequence":"additional","affiliation":[]},{"given":"Andrew C.","family":"Heusser","sequence":"additional","affiliation":[]},{"given":"Jacqueline","family":"Lutz","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"429_CR1","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1093\/ije\/dyt261","volume":"43","author":"GV Polanczyk","year":"2014","unstructured":"Polanczyk, G. V., Willcutt, E. G., Salum, G. A., Kieling, C. & Rohde, L. A. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int. J. Epidemiol. 43, 434\u2013442 (2014).","journal-title":"Int. J. Epidemiol."},{"key":"429_CR2","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.jval.2017.01.007","volume":"20","author":"K Gupte-Singh","year":"2017","unstructured":"Gupte-Singh, K., Singh, R. R. & Lawson, K. A. Economic burden of attention-deficit\/hyperactivity disorder among pediatric patients in the United States. Value Heal. 20, 602\u2013609 (2017).","journal-title":"Value Heal."},{"key":"429_CR3","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1037\/a0027347","volume":"121","author":"EG Willcutt","year":"2012","unstructured":"Willcutt, E. G. et al. Validity of DSM-IV attention deficit\/hyperactivity disorder symptom dimensions and subtypes. J. Abnorm. Psychol. 121, 991\u20131010 (2012).","journal-title":"J. Abnorm. Psychol."},{"key":"429_CR4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180355","volume":"12","author":"F Catal\u00e1-L\u00f3pez","year":"2017","unstructured":"Catal\u00e1-L\u00f3pez, F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: a systematic review with network meta-analyses of randomised trials. PLoS ONE 12, e0180355 (2017).","journal-title":"PLoS ONE"},{"key":"429_CR5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","volume":"5","author":"S Cortese","year":"2018","unstructured":"Cortese, S. 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. Lancet Psychiatry 5, 727\u2013738 (2018).","journal-title":"Lancet Psychiatry"},{"key":"429_CR6","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1001\/jamapediatrics.2018.1642","volume":"172","author":"SH Kollins","year":"2018","unstructured":"Kollins, S. H. Moving beyond symptom remission to optimize long-term treatment of attention-deficit\/hyperactivity disorder. JAMA Pediatrics 172, 901\u2013902 (2018).","journal-title":"JAMA Pediatrics"},{"key":"429_CR7","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1177\/0009922812446744","volume":"51","author":"SL Toomey","year":"2012","unstructured":"Toomey, S. L., Sox, C. M., Rusinak, D. & Finkelstein, J. A. Why do children with ADHD discontinue their medication? Clin. Pediatr. 51, 763\u2013769 (2012).","journal-title":"Clin. Pediatr."},{"key":"429_CR8","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1089\/cap.2017.0166","volume":"28","author":"M Weiss","year":"2018","unstructured":"Weiss, M. et al. Relationship between symptomatic and functional improvement and remission in a treatment response to stimulant trial. J. Child Adolesc. Psychopharmacol. 28, 521\u2013529 (2018).","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"429_CR9","unstructured":"Health Resources & Services Administration. Shortage areas. https:\/\/data.hrsa.gov\/topics\/health-workforce\/shortage-areas (2019). Accessed 6th Dec 2019."},{"key":"429_CR10","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1007\/BF02289806","volume":"30","author":"R Bussing","year":"2003","unstructured":"Bussing, R., Zima, B. T., Gary, F. A. & Garvan, C. W. Barriers to detection, help-seeking, and service use for children with ADHD symptoms. J. Behav. Heal. Serv. Res. 30, 176\u2013189 (2003).","journal-title":"J. Behav. Heal. Serv. Res."},{"key":"429_CR11","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1097\/00004583-200206000-00013","volume":"41","author":"PL Owens","year":"2002","unstructured":"Owens, P. L. et al. Barriers to Children\u2019s Mental Health Services. J. Am. Acad. Child Adolesc. Psychiatry 41, 731\u2013738 (2002).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR12","doi-asserted-by":"crossref","unstructured":"Danielson, M. L. et al. Prevalence of parent-reported ADHD diagnosis and associated treatment among U.S. children and adolescents. 47, 199\u2013212 (2018).","DOI":"10.1080\/15374416.2017.1417860"},{"key":"429_CR13","unstructured":"Davies, S. C. Annual report of the Chief Medical Officer 2013, Public Mental health priorities: investing in the evidence (Department of Health, London, 2014)"},{"key":"429_CR14","doi-asserted-by":"publisher","first-page":"e168","DOI":"10.1016\/S2589-7500(20)30017-0","volume":"2","author":"SH Kollins","year":"2020","unstructured":"Kollins, S. H. et al. A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. Lancet Digit. Heal. 2, e168\u2013e178 (2020).","journal-title":"Lancet Digit. Heal."},{"key":"429_CR15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/00004583-200102000-00010","volume":"40","author":"CK Conners","year":"2001","unstructured":"Conners, C. K. et al. Multimodal treatment of ADHD in the MTA: An alternative outcome analysis. J. Am. Acad. Child Adolesc. Psychiatry 40, 159\u2013167 (2001).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR16","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1542\/peds.2011-2654","volume":"128","author":"Subcommittee on Attention-Deficit\/Hyperactivity Disorder, S. O. A.-D.","year":"2011","unstructured":"Subcommittee on Attention-Deficit\/Hyperactivity Disorder, S. O. A.-D. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit\/hyperactivity disorder in children and adolescents. Pediatrics 128, 1007\u20131022 (2011).","journal-title":"Pediatrics"},{"key":"429_CR17","doi-asserted-by":"publisher","first-page":"115","DOI":"10.5765\/jkacap.2017.28.2.115","volume":"28","author":"EK Lee","year":"2017","unstructured":"Lee, E. K., Kim, H. S. & Yoo, H. K. Augmentative effects of working memory training on behavioral problems and parental stress in medicated children and adolescents with attention-deficit hyperactivity disorder. J. Korean Acad. Child Adolesc. Psychiatry 28, 115\u2013122 (2017).","journal-title":"J. Korean Acad. Child Adolesc. Psychiatry"},{"key":"429_CR18","doi-asserted-by":"publisher","unstructured":"de Oliveira Rosa, V. et al. Computerized cognitive training for ADHD as an add-on treatment to stimulants: a Randomized Clinical Trial. J. Atten. Disord. https:\/\/doi.org\/10.1177\/1087054718816818 (2018).","DOI":"10.1177\/1087054718816818"},{"key":"429_CR19","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1542\/peds.113.4.754","volume":"113","author":"MTA Cooperative Group.","year":"2004","unstructured":"MTA Cooperative Group. National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit\/hyperactivity disorder. Pediatrics 113, 754\u2013761 (2004).","journal-title":"Pediatrics"},{"key":"429_CR20","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1097\/01.chi.0000128791.10014.ac","volume":"43","author":"H Abikoff","year":"2004","unstructured":"Abikoff, H. et al. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. J. Am. Acad. Child Adolesc. Psychiatry 43, 802\u2013811 (2004).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR21","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1097\/01.chi.0000173291.28688.e7","volume":"44","author":"T Wilens","year":"2005","unstructured":"Wilens, T. et al. ADHD treatment with once-daily OROS methylphenidate: final results from a long-term open-label study. J. Am. Acad. Child Adolesc. Psychiatry 44, 1015\u20131023 (2005).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR22","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/00004583-200102000-00013","volume":"40","author":"B Vitiello","year":"2001","unstructured":"Vitiello, B. et al. Methylphenidate dosage for children with ADHD over time under controlled conditions: Lessons from the MTA. J. Am. Acad. Child Adolesc. Psychiatry 40, 188\u2013196 (2001).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR23","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.jaac.2018.11.013","volume":"58","author":"JJ McGough","year":"2019","unstructured":"McGough, J. J. et al. Double-Blind, Sham-Controlled, Pilot Study of trigeminal nerve stimulation for ADHD. J. Am. Acad. Child Adolesc. Psychiatry 58, 403\u2013411.e3 (2019).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"429_CR24","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1177\/1087054715577138","volume":"24","author":"JM Langberg","year":"2020","unstructured":"Langberg, J. M. & Becker, S. P. ADHD treatment and long-term academic outcomes: response to Arnold and Colleagues. J. Atten. Disord. 24, 819\u2013820 (2020).","journal-title":"J. Atten. Disord."},{"key":"429_CR25","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s10567-012-0117-8","volume":"15","author":"JM Langberg","year":"2012","unstructured":"Langberg, J. M. & Becker, S. P. Does long-term medication use improve the academic outcomes of youth with attention-deficit\/hyperactivity disorder? Clin. Child Fam. Psychol. Rev. 15, 215\u2013233 (2012).","journal-title":"Clin. Child Fam. Psychol. Rev."},{"key":"429_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0172616","volume":"12","author":"JA Anguera","year":"2017","unstructured":"Anguera, J. A. et al. A pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory processing dysfunction. PLoS ONE 12, 1\u201319 (2017).","journal-title":"PLoS ONE"},{"key":"429_CR27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nature12486","volume":"501","author":"JA Anguera","year":"2013","unstructured":"Anguera, J. A. et al. Video game training enhances cognitive control in older adults. Nature 501, 97\u2013101 (2013).","journal-title":"Nature"},{"key":"429_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41746-020-00314-2","volume":"3","author":"C Guo","year":"2020","unstructured":"Guo, C. et al. Challenges for the evaluation of digital health solutions\u2014a call for innovative evidence generation approaches. npj Digit. Med. 3, 1\u201314 (2020).","journal-title":"npj Digit. Med."},{"key":"429_CR29","doi-asserted-by":"crossref","unstructured":"Chew, A. M. K. et al. Digital Health Solutions for mental health disorders during COVID-19. Front. Psychiatry 11, 582007 (2020).","DOI":"10.3389\/fpsyt.2020.582007"},{"key":"429_CR30","doi-asserted-by":"publisher","unstructured":"Beede, E. et al. A human-centered evaluation of a deep learning system deployed in clinics for the detection of diabetic retinopathy. in Proc. Conference on Human Factors in Computing Systems 1\u201312 (Association for Computing Machinery, 2020). https:\/\/doi.org\/10.1145\/3313831.3376718.","DOI":"10.1145\/3313831.3376718"},{"key":"429_CR31","doi-asserted-by":"publisher","DOI":"10.2196\/17417","volume":"22","author":"DV Gunasekeran","year":"2020","unstructured":"Gunasekeran, D. V. et al. Evaluating safety and efficacy of follow-up for patients with abdominal pain using video consultation (SAVED Study): randomized controlled trial. J. Med. Internet Res. 22, e17417 (2020).","journal-title":"J. Med. Internet Res."},{"key":"429_CR32","doi-asserted-by":"crossref","unstructured":"Richards, D. et al. A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety. npj Digit. Med. 3, 85 (2020).","DOI":"10.1038\/s41746-020-0293-8"},{"key":"429_CR33","first-page":"1","volume":"13","author":"NO Davis","year":"2018","unstructured":"Davis, N. O., Bower, J. & Kollins, S. H. Proof-of-concept study of an at-home, engaging, digital intervention for pediatric ADHD. PLoS ONE 13, 1\u201319 (2018).","journal-title":"PLoS ONE"}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-021-00429-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-021-00429-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-021-00429-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T18:48:22Z","timestamp":1670093302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-021-00429-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,26]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["429"],"URL":"https:\/\/doi.org\/10.1038\/s41746-021-00429-0","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,26]]},"assertion":[{"value":"11 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Akili Interactive Labs provided research support for this study and played a role in the conceptualization and design of the trial and in the decision to publish and manuscript preparation. In addition, the authors declare the following employment and financial interests: J.L. and A.C.H. are Employees at Akili Interactive and own Stock or Equity. S.H.K. is a Consultant for Akili Interactive, owns Stock or Equity, and received Research support. A.C. served on the Advisory Board and received Research support. The views and opinions expressed within this manuscript are those of all the authors and do not necessarily represent those of the sponsor.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}