{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:34:46Z","timestamp":1783794886518,"version":"3.55.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integrating <jats:italic>CYP2D6<\/jats:italic> genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit\/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their <jats:italic>CYP2D6<\/jats:italic> genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the <jats:italic>CYP2D6<\/jats:italic> genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and &lt;18, who visited the psychological and behavioral clinic of Children\u2019s Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including <jats:italic>CYP2D6<\/jats:italic> genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, &gt;60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while &lt;40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, <jats:italic>P<\/jats:italic>\u2009=\u20090.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (<jats:italic>q.m<\/jats:italic>.) dosing regimen exhibited a more effective response to atomoxetine when their levels were \u2265 268\u2009ng\/mL (AUC\u2009=\u20090.710, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In addition, CYP2D6 IMs receiving <jats:italic>q.m<\/jats:italic>. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509\u2009ng\/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their <jats:italic>CYP2D6<\/jats:italic> genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268\u2009ng\/mL might be requisite for <jats:italic>q.m<\/jats:italic>. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.<\/jats:p>","DOI":"10.1038\/s41398-024-02859-2","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T06:50:29Z","timestamp":1710831029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-8145","authenticated-orcid":false,"given":"Hong-Li","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Dan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Rong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-2350","authenticated-orcid":false,"given":"Ya-Hui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-4682","authenticated-orcid":false,"given":"Qian-Qi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-6762","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"2859_CR1","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/S0140-6736(19)33004-1","volume":"395","author":"J Posner","year":"2020","unstructured":"Posner J, Polanczyk GV, Sonuga-Barke E. Attention-deficit hyperactivity disorder. Lancet. 2020;395:450\u201362.","journal-title":"Lancet"},{"key":"2859_CR2","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1056\/NEJMra1917069","volume":"383","author":"S Cortese","year":"2020","unstructured":"Cortese S. Pharmacologic Treatment of Attention Deficit-Hyperactivity Disorder. N Engl J Med. 2020;383:1050\u20136.","journal-title":"N Engl J Med"},{"key":"2859_CR3","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/wps.21020","volume":"21","author":"L Li","year":"2022","unstructured":"Li L, Chang Z, Sun J, Garcia-Argibay M, Du Rietz E, Dobrosavljevic M, et al. Attention-deficit\/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population-based cohort study. World Psychiatry. 2022;21:452\u20139.","journal-title":"World Psychiatry"},{"key":"2859_CR4","doi-asserted-by":"crossref","unstructured":"Wolraich ML, Hagan JF, Jr, Allan C, Chan E, Davison D, Earls M, et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit\/Hyperactivity Disorder in Children and Adolescents. Pediatrics 2019;144.","DOI":"10.1542\/peds.2019-2528"},{"key":"2859_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-016-1187-9","volume":"17","author":"T Wang","year":"2017","unstructured":"Wang T, Liu K, Li Z, Xu Y, Liu Y, Shi W, et al. Prevalence of attention deficit\/hyperactivity disorder among children and adolescents in China: a systematic review and meta-analysis. BMC Psychiatry. 2017;17:32.","journal-title":"BMC Psychiatry"},{"key":"2859_CR6","doi-asserted-by":"publisher","first-page":"e181471","DOI":"10.1001\/jamanetworkopen.2018.1471","volume":"1","author":"G Xu","year":"2018","unstructured":"Xu G, Strathearn L, Liu B, Yang B, Bao W. Twenty-Year Trends in Diagnosed Attention-Deficit\/Hyperactivity Disorder Among US Children and Adolescents, 1997-2016. JAMA Netw Open. 2018;1:e181471.","journal-title":"JAMA Netw Open"},{"key":"2859_CR7","first-page":"PCC.13r01600","volume":"16","author":"Y Ginsberg","year":"2014","unstructured":"Ginsberg Y, Quintero J, Anand E, Casillas M, Upadhyaya HP. Underdiagnosis of attention-deficit\/hyperactivity disorder in adult patients: a review of the literature. Prim Care Companion CNS Disord. 2014;16:PCC.13r01600.","journal-title":"Prim Care Companion CNS Disord"},{"key":"2859_CR8","doi-asserted-by":"publisher","first-page":"15020","DOI":"10.1038\/nrdp.2015.20","volume":"1","author":"SV Faraone","year":"2015","unstructured":"Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, et al. Attention-deficit\/hyperactivity disorder. Nat Rev Dis Primers. 2015;1:15020.","journal-title":"Nat Rev Dis Primers"},{"key":"2859_CR9","doi-asserted-by":"publisher","first-page":"04009","DOI":"10.7189\/jogh.11.04009","volume":"11","author":"P Song","year":"2021","unstructured":"Song P, Zha M, Yang Q, Zhang Y, Li X, Rudan I. The prevalence of adult attention-deficit hyperactivity disorder: A global systematic review and meta-analysis. J Glob Health. 2021;11:04009.","journal-title":"J Glob Health"},{"key":"2859_CR10","first-page":"349","volume":"79","author":"D Fu","year":"2023","unstructured":"Fu D, Guo HL, Hu YH, Fang WR, Liu QQ, Xu J, et al. Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence. Eur J Clin Pharmacol. 2023;79:349\u201370.","journal-title":"Eur J Clin Pharmacol"},{"key":"2859_CR11","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1097\/CHI.0b013e31819c55b2","volume":"48","author":"JH Newcorn","year":"2009","unstructured":"Newcorn JH, Sutton VK, Weiss MD, Sumner CR. Clinical responses to atomoxetine in attention-deficit\/hyperactivity disorder: the Integrated Data Exploratory Analysis (IDEA) study. J Am Acad Child Adolesc Psychiatry. 2009;48:511\u20138.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2859_CR12","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1002\/cpt.319","volume":"99","author":"JT Brown","year":"2016","unstructured":"Brown JT, Abdel-Rahman SM, van Haandel L, Gaedigk A, Lin YS, Leeder JS. Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD. Clin Pharmacol Ther. 2016;99:642\u201350.","journal-title":"Clin Pharmacol Ther"},{"key":"2859_CR13","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/brainsci11010091","volume":"11","author":"PC Mamiya","year":"2021","unstructured":"Mamiya PC, Arnett AB, Stein MA. Precision Medicine Care in ADHD: The Case for Neural Excitation and Inhibition. Brain Sci. 2021;11:91.","journal-title":"Brain Sci"},{"key":"2859_CR14","doi-asserted-by":"publisher","first-page":"107940","DOI":"10.1016\/j.pharmthera.2021.107940","volume":"230","author":"K Mechler","year":"2022","unstructured":"Mechler K, Banaschewski T, Hohmann S, Hage A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacol Ther. 2022;230:107940.","journal-title":"Pharmacol Ther"},{"key":"2859_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.780921","volume":"12","author":"D Fu","year":"2021","unstructured":"Fu D, Wu DD, Guo HL, Hu YH, Xia Y, Ji X, et al. The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review. Front Psychiatry. 2021;12:780921.","journal-title":"Front Psychiatry"},{"key":"2859_CR16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1055\/s-0043-116492","volume":"51","author":"C Hiemke","year":"2018","unstructured":"Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51:9\u201362.","journal-title":"Pharmacopsychiatry"},{"key":"2859_CR17","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/cpt.1409","volume":"106","author":"JT Brown","year":"2019","unstructured":"Brown JT, Bishop JR, Sangkuhl K, Nurmi EL, Mueller DJ, Dinh JC, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy. Clin Pharmacol Ther. 2019;106:94\u2013102.","journal-title":"Clin Pharmacol Ther"},{"key":"2859_CR18","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/s41431-022-01262-z","volume":"31","author":"M Nijenhuis","year":"2022","unstructured":"Nijenhuis M, Soree B, Jama WOM, de Boer-Veger NJ, Buunk AM, Guchelaar HJ, et al. Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction of CYP2D6 and COMT with atomoxetine and methylphenidate. Eur J Hum Genet. 2022;31:1364\u201370.","journal-title":"Eur J Hum Genet"},{"key":"2859_CR19","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1039\/D1AY00521A","volume":"13","author":"Y Xia","year":"2021","unstructured":"Xia Y, Guo HL, Hu YH, Long JY, Chen J, Chen F, et al. Determination of atomoxetine levels in human plasma using LC-MS\/MS and clinical application to Chinese children with ADHD based on CPIC guidelines. Anal Methods. 2021;13:2434\u201341.","journal-title":"Anal Methods"},{"key":"2859_CR20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2174\/1872312815666220113125232","volume":"15","author":"AN Dong","year":"2022","unstructured":"Dong AN, Ahemad N, Pan Y, Palanisamy UD, Yiap BC, Ong CE. Role of P34S, G169R, R296C, and S486T Substitutions in Ligand Access and Catalysis for Cytochrome P450 2D6 Allelic Variants CYP2D6*14A and CYP2D6*14B. Drug Metab Bioanal Lett. 2022;15:51\u201363.","journal-title":"Drug Metab Bioanal Lett"},{"key":"2859_CR21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/sj.clpt.6100015","volume":"81","author":"WM Cai","year":"2007","unstructured":"Cai WM, Chen B, Zhang WX. Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic activity of CYP2D6 in a healthy Chinese population. Clin Pharmacol Ther. 2007;81:95\u20138.","journal-title":"Clin Pharmacol Ther"},{"key":"2859_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106290","volume":"81","author":"HL Guo","year":"2020","unstructured":"Guo HL, Xu J, Sun JY, Li L, Guo HL, Jing X, et al. Tacrolimus treatment in childhood refractory nephrotic syndrome: A retrospective study on efficacy, therapeutic drug monitoring, and contributing factors to variable blood tacrolimus levels. Int Immunopharmacol. 2020;81:106290.","journal-title":"Int Immunopharmacol"},{"key":"2859_CR23","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/01.chi.0000246056.83791.b6","volume":"46","author":"D Michelson","year":"2007","unstructured":"Michelson D, Read HA, Ruff DD, Witcher J, Zhang S, McCracken J. CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry. 2007;46:242\u201351.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2859_CR24","doi-asserted-by":"publisher","first-page":"e26552","DOI":"10.1097\/MD.0000000000026552","volume":"100","author":"A Sugimoto","year":"2021","unstructured":"Sugimoto A, Suzuki Y, Orime N, Hayashi T, Yoshinaga K, Egawa J, et al. The lowest effective plasma concentration of atomoxetine in pediatric patients with attention deficit\/hyperactivity disorder: A non-randomized prospective interventional study. Medicine (Baltimore). 2021;100:e26552.","journal-title":"Medicine (Baltimore)"},{"key":"2859_CR25","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1007\/s00702-022-02483-8","volume":"129","author":"K Ruppert","year":"2022","unstructured":"Ruppert K, Geffert C, Clement HW, Bachmann C, Haberhausen M, Schulz E, et al. Therapeutic drug monitoring of atomoxetine in children and adolescents with attention-deficit\/ hyperactivity disorder: a naturalistic study. J Neural Transm (Vienna). 2022;129:945\u201359.","journal-title":"J Neural Transm (Vienna)"},{"key":"2859_CR26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s12402-009-0012-4","volume":"1","author":"P Hazell","year":"2009","unstructured":"Hazell P, Becker K, Nikkanen EA, Trzepacz PT, Tanaka Y, Tabas L, et al. Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit\/hyperactivity disorder and comorbid oppositional defiant disorder. Atten Defic Hyperact Disord. 2009;1:201\u201310.","journal-title":"Atten Defic Hyperact Disord"},{"key":"2859_CR27","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1124\/pharmrev.120.000071","volume":"73","author":"BD van Groen","year":"2021","unstructured":"van Groen BD, Nicolai J, Kuik AC, Van Cruchten S, van Peer E, Smits A, et al. Ontogeny of Hepatic Transporters and Drug-Metabolizing Enzymes in Humans and in Nonclinical Species. Pharmacol Rev. 2021;73:597\u2013678.","journal-title":"Pharmacol Rev"},{"key":"2859_CR28","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.1365-2125.2007.02912.x","volume":"64","author":"YM Cui","year":"2007","unstructured":"Cui YM, Teng CH, Pan AX, Yuen E, Yeo KP, Zhou Y, et al. Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele. Br J Clin Pharmacol. 2007;64:445\u20139.","journal-title":"Br J Clin Pharmacol"},{"key":"2859_CR29","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1177\/0091270011398657","volume":"52","author":"A Matsui","year":"2012","unstructured":"Matsui A, Azuma J, Witcher JW, Long AJ, Sauer JM, Smith BP, et al. Pharmacokinetics, safety, and tolerability of atomoxetine and effect of CYP2D6*10\/*10 genotype in healthy Japanese men. J Clin Pharmacol. 2012;52:388\u2013403.","journal-title":"J Clin Pharmacol"},{"key":"2859_CR30","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1007\/s12272-015-0646-z","volume":"38","author":"JY Byeon","year":"2015","unstructured":"Byeon JY, Kim YH, Na HS, Jang JH, Kim SH, Lee YJ, et al. Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites. Arch Pharm Res. 2015;38:2083\u201391.","journal-title":"Arch Pharm Res"},{"key":"2859_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30841-8","volume":"8","author":"SH Kim","year":"2018","unstructured":"Kim SH, Byeon JY, Kim YH, Lee CM, Lee YJ, Jang CG, et al. Physiologically based pharmacokinetic modelling of atomoxetine with regard to CYP2D6 genotypes. Sci Rep. 2018;8:12405.","journal-title":"Sci Rep"},{"key":"2859_CR32","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.clpt.2004.08.021","volume":"76","author":"Z Bebia","year":"2004","unstructured":"Bebia Z, Buch SC, Wilson JW, Frye RF, Romkes M, Cecchetti A, et al. Bioequivalence revisited: influence of age and sex on CYP enzymes. Clin Pharmacol Ther. 2004;76:618\u201327.","journal-title":"Clin Pharmacol Ther"},{"key":"2859_CR33","doi-asserted-by":"publisher","first-page":"302","DOI":"10.2165\/00003088-199733040-00005","volume":"33","author":"MT Kinirons","year":"1997","unstructured":"Kinirons MT, Crome P. Clinical pharmacokinetic considerations in the elderly. An update. Clin Pharmacokinet. 1997;33:302\u201312.","journal-title":"An update. Clin Pharmacokinet"},{"key":"2859_CR34","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1176\/appi.ajp.159.11.1896","volume":"159","author":"D Michelson","year":"2002","unstructured":"Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry. 2002;159:1896\u2013901.","journal-title":"Am J Psychiatry"},{"key":"2859_CR35","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1177\/0009922809335321","volume":"48","author":"SL Block","year":"2009","unstructured":"Block SL, Kelsey D, Coury D, Lewis D, Quintana H, Sutton V, et al. Once-daily atomoxetine for treating pediatric attention-deficit\/hyperactivity disorder: comparison of morning and evening dosing. Clin Pediatr (Phila). 2009;48:723\u201333.","journal-title":"Clin Pediatr (Phila)"},{"key":"2859_CR36","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1542\/peds.114.1.e1","volume":"114","author":"DK Kelsey","year":"2004","unstructured":"Kelsey DK, Sumner CR, Casat CD, Coury DL, Quintana H, Saylor KE, et al. Once-daily atomoxetine treatment for children with attention-deficit\/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial. Pediatrics. 2004;114:e1\u20138.","journal-title":"Pediatrics"},{"key":"2859_CR37","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1038\/npp.2009.39","volume":"34","author":"N Ramoz","year":"2009","unstructured":"Ramoz N, Boni C, Downing AM, Close SL, Peters SL, Prokop AM, et al. A haplotype of the norepinephrine transporter (Net) gene Slc6a2 is associated with clinical response to atomoxetine in attention-deficit hyperactivity disorder (ADHD). Neuropsychopharmacology. 2009;34:2135\u201342.","journal-title":"Neuropsychopharmacology"},{"key":"2859_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/1753-2000-2-25","volume":"2","author":"CJ Kratochvil","year":"2008","unstructured":"Kratochvil CJ, Milton DR, Vaughan BS, Greenhill LL. Acute atomoxetine treatment of younger and older children with ADHD: a meta-analysis of tolerability and efficacy. Child Adolesc Psychiatry Ment Health. 2008;2:25.","journal-title":"Child Adolesc Psychiatry Ment Health"},{"key":"2859_CR39","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1089\/cap.2014.0001","volume":"25","author":"H Upadhyaya","year":"2015","unstructured":"Upadhyaya H, Kratochvil C, Ghuman J, Camporeale A, Lipsius S, D\u2019Souza D, et al. Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit\/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2015;25:799\u2013809.","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"2859_CR40","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1097\/01.chi.0000190352.90946.0b","volume":"45","author":"TE Wilens","year":"2006","unstructured":"Wilens TE, Kratochvil C, Newcorn JH, Gao H. Do children and adolescents with ADHD respond differently to atomoxetine? J Am Acad Child Adolesc Psychiatry. 2006;45:149\u201357.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2859_CR41","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1097\/chi.0b013e3180335ad1","volume":"46","author":"LL Greenhill","year":"2007","unstructured":"Greenhill LL, Newcorn JH, Gao H, Feldman PD. Effect of two different methods of initiating atomoxetine on the adverse event profile of atomoxetine. J Am Acad Child Adolesc Psychiatry. 2007;46:566\u201372.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2859_CR42","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/10401230600614603","volume":"18","author":"L Adler","year":"2006","unstructured":"Adler L, Dietrich A, Reimherr FW, Taylor LV, Sutton VK, Bakken R, et al. Safety and tolerability of once versus twice daily atomoxetine in adults with ADHD. Ann Clin Psychiatry. 2006;18:107\u201313.","journal-title":"Ann Clin Psychiatry"},{"key":"2859_CR43","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1177\/009127002762491307","volume":"42","author":"DJ Belle","year":"2002","unstructured":"Belle DJ, Ernest CS, Sauer JM, Smith BP, Thomasson HR, Witcher JW. Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. J Clin Pharmacol. 2002;42:1219\u201327.","journal-title":"J Clin Pharmacol"},{"key":"2859_CR44","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1007\/s12272-020-01300-8","volume":"43","author":"EH Jung","year":"2020","unstructured":"Jung EH, Lee YJ, Kim DH, Kang P, Lim CW, Cho CK, et al. Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes. Arch Pharm Res. 2020;43:1356\u201363.","journal-title":"Arch Pharm Res"},{"key":"2859_CR45","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/JCP.0b013e3182a608a2","volume":"34","author":"CI Choi","year":"2014","unstructured":"Choi CI, Bae JW, Lee YJ, Lee HI, Jang CG, Lee SY. Effects of CYP2C19 genetic polymorphisms on atomoxetine pharmacokinetics. J Clin Psychopharmacol. 2014;34:139\u201342.","journal-title":"J Clin Psychopharmacol"},{"key":"2859_CR46","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1111\/bcp.15706","volume":"89","author":"RL Smith","year":"2023","unstructured":"Smith RL, Molden E, Bernard JP. Effect of CYP2D6 and CYP2C19 genotypes on atomoxetine serum levels: A study based on therapeutic drug monitoring data. Br J Clin Pharmacol. 2023;89:2246\u201353.","journal-title":"Br J Clin Pharmacol"},{"key":"2859_CR47","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3389\/fnins.2018.01051","volume":"12","author":"Z Nemoda","year":"2018","unstructured":"Nemoda Z, Angyal N, Tarnok Z, Birkas E, Bognar E, Sasvari-Szekely M, et al. Differential Genetic Effect of the Norepinephrine Transporter Promoter Polymorphisms on Attention Problems in Clinical and Non-clinical Samples. Front Neurosci. 2018;12:1051.","journal-title":"Front Neurosci"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02859-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02859-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02859-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T07:02:53Z","timestamp":1710831773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02859-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2859"],"URL":"https:\/\/doi.org\/10.1038\/s41398-024-02859-2","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]},"assertion":[{"value":"31 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None of the authors have any conflicts of interest to disclose. We confirm that we have read the Journal\u2019s position on issues involved in ethical publications and affirm that this report is in consistent with those guidelines.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"151"}}