{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:51:39Z","timestamp":1792151499015,"version":"4.4.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Freiburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neural Transm"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural\/emotional\/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age\u2009=\u200915.2\u2009\u00b1\u20092.6, range\u2009=\u20097.4\u201318.2 years, females\u2009=\u200953%, CGI-Severity\u2009=\u20094.4\u2009\u00b1\u20091.1, responders\u2009=\u200964%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean\u2009\u00b1\u2009SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100\u2013230 ng\/ml) compared to adult schizophrenia-spectrum disorders patients (100\u2013350 ng\/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60\u2013160 ng\/ml and for patients with behavioural\/tic disorders 60\u2013140 ng\/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural\/tic disorder diagnoses.<\/jats:p>","DOI":"10.1007\/s00702-024-02819-6","type":"journal-article","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T10:02:40Z","timestamp":1730541760000},"page":"295-312","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic drug monitoring in children and adolescents with schizophrenia-spectrum, affective, behavioural, tic and other psychiatric disorders treated with aripiprazole: results of the TDM-VIGIL pharmacovigilance study"],"prefix":"10.1007","volume":"132","author":[{"given":"Jessica","family":"Riegger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Maria","family":"Egberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Willi","family":"Clement","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Schneider-Momm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Taurines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Fekete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wewetzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Karwautz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Plener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Malzahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heuschmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Unterecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Scherf-Clavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Rock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Antony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Briegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Banaschewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Hellenschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kaess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"K\u00f6lch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Rexroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Schulte-K\u00f6rne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Walitza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Gerlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Romanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Fleischhaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"issue":"5","key":"2819_CR1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1089\/cap.2015.0141","volume":"26","author":"Z Al-Dhaher","year":"2016","unstructured":"Al-Dhaher Z, Kapoor S, Saito E, Krakower S, David L, Ake T, Kane JM, Correll CU, Carbon M (2016) Activating and tranquilizing effects of First-Time treatment with Aripiprazole, Olanzapine, Quetiapine, and Risperidone in Youth. J Child Adolesc Psychopharmacol 26(5):458\u2013470","journal-title":"J Child Adolesc Psychopharmacol"},{"issue":"4","key":"2819_CR2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/FTD.0b013e318178e18d","volume":"30","author":"CJ Bachmann","year":"2008","unstructured":"Bachmann CJ, Rieger-Gies A, Heinzel-Gutenbrunner M, Hiemke C, Remschmidt H, Theisen FM (2008) Large variability of aripiprazole and dehydroaripiprazole serum concentrations in adolescent patients with schizophrenia. Ther Drug Monit 30(4):462\u2013466","journal-title":"Ther Drug Monit"},{"issue":"6","key":"2819_CR3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1055\/s-2004-832687","volume":"37","author":"P Baumann","year":"2004","unstructured":"Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M, Kuss H-J, Laux G, M\u00fcller-Oerlinghausen B, Rao ML, Riederer P, Zernig G (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37(6):243\u2013265","journal-title":"Pharmacopsychiatry"},{"issue":"9","key":"2819_CR4","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jaac.2015.06.015","volume":"54","author":"M Carbon","year":"2015","unstructured":"Carbon M, Kapoor S, Sheridan E, Al-Jadiri A, Azzo S, Sarkaria T, Kane JM, Saito E, Correll CU (2015) Neuromotor adverse effects in 342 Youth during 12 weeks of naturalistic treatment with 5 second-generation antipsychotics. J Am Acad Child Adolesc Psychiatry 54(9):718\u2013727e3","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"1","key":"2819_CR5","first-page":"77","volume":"40","author":"RR Conley","year":"2007","unstructured":"Conley RR, Kelly DL (2007) Drug-drug interactions associated with second-generation antipsychotics: considerations for clinicians and patients. Psychopharmacol Bull 40(1):77\u201397","journal-title":"Psychopharmacol Bull"},{"issue":"8","key":"2819_CR6","doi-asserted-by":"crossref","first-page":"e028680","DOI":"10.1136\/bmjopen-2018-028680","volume":"9","author":"RL Conn","year":"2019","unstructured":"Conn RL, Kearney O, Tully MP, Shields MD, Dornan T (2019) What causes prescribing errors in children? Scoping review. BMJ open 9(8):e028680","journal-title":"BMJ open"},{"issue":"5","key":"2819_CR7","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.clinthera.2010.04.021","volume":"32","author":"RJ Constantine","year":"2010","unstructured":"Constantine RJ, Boaz T, Tandon R (2010) Antipsychotic polypharmacy in the treatment of children and adolescents in the fee-for-service component of a large state Medicaid program. Clin Ther 32(5):949\u2013959","journal-title":"Clin Ther"},{"issue":"7","key":"2819_CR8","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/01.chi.0000220851.94392.30","volume":"45","author":"CU Correll","year":"2006","unstructured":"Correll CU, Carlson HE (2006) Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry 45(7):771\u2013791","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"9","key":"2819_CR9","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.jaac.2017.06.013","volume":"56","author":"CU Correll","year":"2017","unstructured":"Correll CU, Kohegyi E, Zhao C, Baker RA, McQuade R, Salzman PM, Sanchez R, Nyilas M, Carson W (2017) Oral aripiprazole as maintenance treatment in adolescent Schizophrenia: results from a 52-Week, Randomized, Placebo-Controlled Withdrawal Study. J Am Acad Child Adolesc Psychiatry 56(9):784\u2013792","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"1","key":"2819_CR12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1024\/1422-4917\/a000329","volume":"43","author":"K Egberts","year":"2015","unstructured":"Egberts K, Karwautz A, Plener PL, Mehler-Wex C, K\u00f6lch M, Dang S-Y, Taurines R, Romanos M, Gerlach M (2015) Pharmakovigilanz in Der kinder- und jugendpsychiatrie (Pharmacovigilance in child and adolescent psychiatry). Z fur Kinder- und Jugendpsychiatrie Und Psychother 43(1):21\u201328","journal-title":"Z fur Kinder- und Jugendpsychiatrie Und Psychother"},{"issue":"12","key":"2819_CR13","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00702-020-02253-4","volume":"127","author":"K Egberts","year":"2020","unstructured":"Egberts K, Reuter-Dang S, Fekete S, Kulpok C, Mehler-Wex C, Wewetzer C, Karwautz A, Mitterer M, Holtkamp K, Boege I, Burger R, Romanos M, Gerlach M, Taurines R (2020) Therapeutic drug monitoring of children and adolescents treated with aripiprazole: observational results from routine patient care. J Neural Transmission (Vienna Austria: 1996) 127(12):1663\u20131674","journal-title":"J Neural Transmission (Vienna Austria: 1996)"},{"issue":"2","key":"2819_CR10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1024\/1422-4917\/a000845","volume":"50","author":"K Egberts","year":"2021","unstructured":"Egberts K, Fekete S, H\u00e4ge A, Hiemke C, Scherf-Clavel M, Taurines R, Unterecker S, Gerlach M, Romanos M (2021) Therapeutisches Drug Monitoring Zur Optimierung Der Psychopharmakotherapie Von Kindern Und Jugendlichen (therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - update and guidelines for practice). Z fur Kinder- und Jugendpsychiatrie Und Psychother 50(2):133\u2013152","journal-title":"Z fur Kinder- und Jugendpsychiatrie Und Psychother"},{"issue":"5","key":"2819_CR11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1055\/a-1716-1856","volume":"55","author":"K Egberts","year":"2022","unstructured":"Egberts K, Gerlach M, Correll CU, Plener PL, Malzahn U, Heuschmann P, Unterecker S, Scherf-Clavel M, Rock H, Antony G, Briegel W, Fleischhaker C, H\u00e4ge A, Hellenschmidt T, Imgart H, Kaess M, Karwautz A, K\u00f6lch M, Reitzle K, Renner T, Reuter-Dang S-Y, Rexroth C, Schulte-K\u00f6rne G, Theisen FM, Walitza S, Wewetzer C, Fekete S, Taurines R, Romanos M (2022) Serious adverse drug reactions in children and adolescents treated On- and off-label with antidepressants and antipsychotics in clinical practice. Pharmacopsychiatry 55(5):255\u2013265","journal-title":"Pharmacopsychiatry"},{"issue":"4","key":"2819_CR15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/JCP.0b013e31817dd520","volume":"28","author":"RL Findling","year":"2008","unstructured":"Findling RL, Kauffman RE, Sallee FR, Carson WH, Nyilas M, Mallikaarjun S, Shoaf SE, Forbes RA, Boulton DW, Pikalov A (2008) Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: an open-label, dose-escalation study. J Clin Psychopharmacol 28(4):441\u2013446","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"2819_CR14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/bdi.12042","volume":"15","author":"RL Findling","year":"2013","unstructured":"Findling RL, Correll CU, Nyilas M, Forbes RA, McQuade RD, Jin N, Ivanova S, Mankoski R, Carson WH, Carlson GA (2013) Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study. Bipolar Disord 15(2):138\u2013149","journal-title":"Bipolar Disord"},{"key":"2819_CR17","volume-title":"Psychiatric drugs in children and adolescents","year":"2014","unstructured":"Gerlach M, Warnke A, Greenhill L (eds) (2014) Psychiatric drugs in children and adolescents. Springer Vienna, Vienna"},{"issue":"11","key":"2819_CR16","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1080\/14740338.2016.1225721","volume":"15","author":"M Gerlach","year":"2016","unstructured":"Gerlach M, Egberts K, Dang S-Y, Plener PL, Taurines R, Mehler-Wex C, Romanos M (2016) Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry. Exp Opin Drug Saf 15(11):1477\u20131482","journal-title":"Exp Opin Drug Saf"},{"key":"2819_CR18","doi-asserted-by":"crossref","unstructured":"Guy W (1976) Clinical global impressions. ECDEU Assessment Manual for psychopharmacology \u2013 revised. US Department of Health, Education, and Welfare; Psychopharmacology Research Branch. Division of Extramural Research Programs, pp 218\u2013222","DOI":"10.1037\/e591322011-001"},{"key":"2819_CR20","unstructured":"Hart XM, Gr\u00fcnder G, Zurek G, Sputtek A (2020) P6.6 Comparative study of suggested reference values and observed distributions in daily routine of a medical laboratory. Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP 2020"},{"key":"2819_CR19","doi-asserted-by":"crossref","first-page":"787043","DOI":"10.3389\/fpsyt.2021.787043","volume":"12","author":"XM Hart","year":"2021","unstructured":"Hart XM, Eichentopf L, Lense X, Riemer T, Wesner K, Hiemke C, Gr\u00fcnder G (2021) Therapeutic reference ranges for psychotropic drugs: a protocol for systematic reviews. Front Psychiatry 12:787043","journal-title":"Front Psychiatry"},{"issue":"1","key":"2819_CR21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/FTD.0000000000000018","volume":"36","author":"M Hendset","year":"2014","unstructured":"Hendset M, Molden E, Knape M, Hermann M (2014) Serum concentrations of risperidone and aripiprazole in subgroups encoding CYP2D6 intermediate metabolizer phenotype. Ther Drug Monit 36(1):80\u201385","journal-title":"Ther Drug Monit"},{"issue":"2","key":"2819_CR22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/FTD.0000000000000582","volume":"41","author":"C Hiemke","year":"2019","unstructured":"Hiemke C (2019) Concentration-Effect relationships of psychoactive drugs and the Problem to calculate therapeutic reference ranges. Ther Drug Monit 41(2):174\u2013179","journal-title":"Ther Drug Monit"},{"issue":"6","key":"2819_CR23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1055\/s-0031-1286287","volume":"44","author":"C Hiemke","year":"2011","unstructured":"Hiemke C, Baumann P, Bergemann N, Conca A, Dietmaier O, Egberts K, Fric M, Gerlach M, Greiner C, Gr\u00fcnder G, Haen E, Havemann-Reinecke U, Jaquenoud SE, Kirchherr H, Laux G, Lutz UC, Messer T, M\u00fcller JM, Pfuhlmann B, Rambeck B, Riederer P, Schoppek B, Stingl J, Uhr M, Ulrich S, Waschgler R, Zernig G (2011) AGNP Consensus guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry 44(6):195\u2013235","journal-title":"Pharmacopsychiatry"},{"issue":"1\u201302","key":"2819_CR24","first-page":"9","volume":"51","author":"C Hiemke","year":"2018","unstructured":"Hiemke C, Bergemann N, Clement H-W, Conca A, Deckert J, Domschke K, Eckermann G, Egberts K, Gerlach M, Greiner C, Gr\u00fcnder G, Haen E, Havemann-Reinecke U, Hefner G, Helmer R, Janssen G, Jaquenoud SE, Laux G, Messer T, M\u00f6ssner R, M\u00fcller JM, Paulzen M, Pfuhlmann B, Riederer P, Saria A, Schoppek B, Schoretsanitis G, Schwarz M, Gracia MS, Stegmann B, Steimer W, Stingl J, Uhr M, Ulrich S, Unterecker S, Waschgler R, Zernig G, Zurek G, Baumann P (2018) Consensus guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry 51(1\u201302):9\u201362","journal-title":"Pharmacopsychiatry"},{"issue":"3","key":"2819_CR25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0014-2999(02)01532-7","volume":"441","author":"S Jordan","year":"2002","unstructured":"Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA (2002) The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol 441(3):137\u2013140","journal-title":"Eur J Pharmacol"},{"issue":"9","key":"2819_CR26","doi-asserted-by":"crossref","first-page":"763","DOI":"10.4088\/JCP.v63n0903","volume":"63","author":"JM Kane","year":"2002","unstructured":"Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito G, Zimbroff DL, Ali M (2002) Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 63(9):763\u2013771","journal-title":"J Clin Psychiatry"},{"key":"2819_CR27","unstructured":"Kapfhammer H-P, Karwautz A, Sachs G (2010) Arzneimittelprofil Psychatrie. Aripiprazol. Medizin Median Austria"},{"issue":"9","key":"2819_CR28","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1176\/appi.ajp.160.9.1651","volume":"160","author":"PE Keck","year":"2003","unstructured":"Keck PE, Marcus RN, Tourkodimitris S, Ali M, Liebeskind A, Saha AR, Ingenito G (2003) A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 160(9):1651\u20131658","journal-title":"Am J Psychiatry"},{"issue":"6","key":"2819_CR29","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/j.1365-2125.2008.03223.x","volume":"66","author":"J-R Kim","year":"2008","unstructured":"Kim J-R, Seo H-B, Cho J-Y, Kang D-H, Kim YK, Bahk W-M, Yu K-S, Shin S-G, Kwon JS, Jang I-J (2008) Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. Br J Clin Pharmacol 66(6):802\u2013810","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"2819_CR30","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1080\/15622970701361255","volume":"9","author":"KM Kirschbaum","year":"2008","unstructured":"Kirschbaum KM, M\u00fcller JM, Malevani J, Mobascher A, Burchardt C, Piel M, Hiemke C (2008) Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects. World J Biol Psychiatry: Official J World Federation Soc Biol Psychiatry 9(3):212\u2013218","journal-title":"World J Biol Psychiatry: Official J World Federation Soc Biol Psychiatry"},{"issue":"7","key":"2819_CR31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1080\/14740338.2020.1770224","volume":"19","author":"SM Kloosterboer","year":"2020","unstructured":"Kloosterboer SM, Vierhout D, Stojanova J, Egberts K, Gerlach M, Dieleman GC, Hillegers MHJ, Passe KM, van Gelder T, Dierckx B, Koch BCP (2020) Psychotropic drug concentrations and clinical outcomes in children and adolescents: a systematic review. Exp Opin Drug Saf 19(7):873\u2013890","journal-title":"Exp Opin Drug Saf"},{"issue":"3","key":"2819_CR32","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/bcp.14465","volume":"87","author":"SM Kloosterboer","year":"2021","unstructured":"Kloosterboer SM, de Winter BCM, Reichart CG, Kouijzer MEJ, de Kroon MMJ, van Daalen E, Ester WA, Rieken R, Dieleman GC, van Altena D, Bartelds B, van Schaik RHN, Nasserinejad K, Hillegers MHJ, van Gelder T, Dierckx B, Koch BCP (2021) Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder. Br J Clin Pharmacol 87(3):1069\u20131081","journal-title":"Br J Clin Pharmacol"},{"issue":"9","key":"2819_CR33","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.jaac.2023.03.007","volume":"62","author":"MT Koch","year":"2023","unstructured":"Koch MT, Carlson HE, Kazimi MM, Correll CU (2023) Antipsychotic-related prolactin levels and sexual dysfunction in mentally Ill Youth: a 3-Month Cohort Study. J Am Acad Child Adolesc Psychiatry 62(9):1021\u20131050","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"2","key":"2819_CR34","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/cap.2010.0020","volume":"22","author":"LA Kryzhanovskaya","year":"2012","unstructured":"Kryzhanovskaya LA, Xu W, Millen BA, Acharya N, Jen KY, Osuntokun O (2012) Comparison of long-term (at least 24 weeks) weight gain and metabolic changes between adolescents and adults treated with olanzapine. J Child Adolesc Psychopharmacol 22(2):157\u2013165","journal-title":"J Child Adolesc Psychopharmacol"},{"issue":"34","key":"2819_CR35","doi-asserted-by":"crossref","first-page":"e4654","DOI":"10.1097\/MD.0000000000004654","volume":"95","author":"C-H Lai","year":"2016","unstructured":"Lai C-H, Wu Y-T, Chen C-Y, Hou Y-C (2016) Gray Matter increases in fronto-parietal regions of depression patients with aripiprazole monotherapy: an exploratory study. Medicine 95(34):e4654","journal-title":"Medicine"},{"issue":"6","key":"2819_CR36","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/JCP.0b013e3182356255","volume":"31","author":"S-K Lin","year":"2011","unstructured":"Lin S-K, Chen C-K, Liu Y-L (2011) Aripiprazole and dehydroaripiprazole plasma concentrations and clinical responses in patients with schizophrenia. J Clin Psychopharmacol 31(6):758\u2013762","journal-title":"J Clin Psychopharmacol"},{"key":"2819_CR37","doi-asserted-by":"crossref","unstructured":"March J, Karayal O, Chrisman A (2007) CAPTN: The pediatric adverse event rating scale. The Scientific Proceedings of the 2007 Annual Meeting of the American Academy of Child and Adolescent Psychiatry: 23\u201328","DOI":"10.1037\/t18687-000"},{"issue":"2","key":"2819_CR38","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/JCP.0b013e31816774f9","volume":"28","author":"RN Marcus","year":"2008","unstructured":"Marcus RN, McQuade RD, Carson WH, Hennicken D, Fava M, Simon JS, Trivedi MH, Thase ME, Berman RM (2008) The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 28(2):156\u2013165","journal-title":"J Clin Psychopharmacol"},{"issue":"2\u20133","key":"2819_CR39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1081\/DMR-120023681","volume":"35","author":"T Mizutani","year":"2003","unstructured":"Mizutani T (2003) PM frequencies of major CYPs in asians and caucasians. Drug Metab Rev 35(2\u20133):99\u2013106","journal-title":"Drug Metab Rev"},{"issue":"6","key":"2819_CR40","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/01.ftd.0000249944.42859.bf","volume":"28","author":"E Molden","year":"2006","unstructured":"Molden E, Lunde H, Lunder N, Refsum H (2006) Pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole in psychiatric patients. Ther Drug Monit 28(6):744\u2013749","journal-title":"Ther Drug Monit"},{"issue":"2","key":"2819_CR41","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/FTD.0b013e31824a31e6","volume":"34","author":"K Nemoto","year":"2012","unstructured":"Nemoto K, Mihara K, Nakamura A, Nagai G, Kagawa S, Suzuki T, Kondo T (2012) Effects of paroxetine on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia. Ther Drug Monit 34(2):188\u2013192","journal-title":"Ther Drug Monit"},{"key":"2819_CR42","unstructured":"Otsuka Pharmaceutical (2020) Abilify. Swissmedic-genehmigte Fachinformation: S. 1\u201310"},{"issue":"1","key":"2819_CR43","first-page":"34","volume":"69","author":"N Ozaki","year":"2015","unstructured":"Ozaki N, Otsuka Pharmaceutical, Kato M, Higuchi T, Ono H, Kamijima K (2015) Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-\u00c5sberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study. J Neuropsychiatry Clin Neurosci 69(1):34\u201342","journal-title":"J Neuropsychiatry Clin Neurosci"},{"issue":"3","key":"2819_CR44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00228-015-1982-0","volume":"72","author":"M Pozzi","year":"2016","unstructured":"Pozzi M, Cattaneo D, Baldelli S, Fucile S, Capuano A, Bravaccio C, Sportiello L, Bertella S, Auricchio F, Bernardini R, Ferrajolo C, Guastella G, Mani E, Carnovale C, Pisano S, Rafaniello C, Riccio MP, Rizzo R, Scuderi MG, Sperandeo S, Villa L, Pascotto A, Molteni M, Rossi F, Radice S, Clementi E (2016) Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: an observational study in real-life settings. Eur J Clin Pharmacol 72(3):285\u2013293","journal-title":"Eur J Clin Pharmacol"},{"issue":"8","key":"2819_CR45","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2165\/11592020-000000000-00000","volume":"34","author":"T Pringsheim","year":"2011","unstructured":"Pringsheim T, Lam D, Ching H, Patten S (2011) Metabolic and neurological complications of second-generation antipsychotic use in children: a systematic review and meta-analysis of randomized controlled trials. Drug Saf 34(8):651\u2013668","journal-title":"Drug Saf"},{"issue":"4","key":"2819_CR46","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1177\/0269881106059693","volume":"20","author":"G Sachs","year":"2006","unstructured":"Sachs G, Sanchez R, Marcus R, Stock E, McQuade R, Carson W, Abou-Gharbia N, Impellizzeri C, Kaplita S, Rollin L, Iwamoto T (2006) Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study. J Psychopharmacol (Oxford England) 20(4):536\u2013546","journal-title":"J Psychopharmacol (Oxford England)"},{"issue":"2","key":"2819_CR47","first-page":"284","volume":"60","author":"C Sachse","year":"1997","unstructured":"Sachse C, Brockm\u00f6ller J, Bauer S, Roots I (1997) Cytochrome P450 2D6 variants in a caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60(2):284\u2013295","journal-title":"Am J Hum Genet"},{"key":"2819_CR48","doi-asserted-by":"crossref","unstructured":"Schoretsanitis G, Kane JM, Correll CU, Marder SR, Citrome L, Newcomer JW, Robinson DG, Goff DC, Kelly DL, Freudenreich O, Piacentino D, Paulzen M, Conca A, Zernig G, Haen E, Baumann P, Hiemke C, Gr\u00fcnder G, Pharmakopsychiatrie TTDMTFOTAFNU (2020) Blood levels to optimize antipsychotic treatment in clinical practice: a Joint Consensus Statement of the American Society of Clinical Psychopharmacology and the therapeutic drug monitoring Task Force of the Arbeitsgemeinschaft f\u00fcr neuropsychopharmakologie und Pharmakopsychiatrie. J Clin Psychiatry 81(3)","DOI":"10.4088\/JCP.19cs13169"},{"issue":"9","key":"2819_CR49","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1089\/cap.2016.0202","volume":"27","author":"C Schr\u00f6der","year":"2017","unstructured":"Schr\u00f6der C, D\u00f6rks M, Kollhorst B, Blenk T, Dittmann RW, Garbe E, Riedel O (2017) Extent and risks of antipsychotic off-label use in children and adolescents in Germany between 2004 and 2011. J Child Adolesc Psychopharmacol 27(9):806\u2013813","journal-title":"J Child Adolesc Psychopharmacol"},{"issue":"7","key":"2819_CR50","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1001\/archpsyc.63.7.721","volume":"63","author":"P Shaw","year":"2006","unstructured":"Shaw P, Sporn A, Gogtay N, Overman GP, Greenstein D, Gochman P, Tossell JW, Lenane M, Rapoport JL (2006) Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry 63(7):721\u2013730","journal-title":"Arch Gen Psychiatry"},{"issue":"1","key":"2819_CR51","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1742-7843.2007.00017.x","volume":"100","author":"E Spina","year":"2007","unstructured":"Spina E, De Leon J (2007) Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol 100(1):4\u201322","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"2","key":"2819_CR52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1055\/s-0030-1267178","volume":"44","author":"V Stieffenhofer","year":"2011","unstructured":"Stieffenhofer V, Saglam H, Schmidtmann I, Silver H, Hiemke C, Konrad A (2011) Clozapine plasma level monitoring for prediction of rehospitalization schizophrenic outpatients. Pharmacopsychiatry 44(2):55\u201359","journal-title":"Pharmacopsychiatry"},{"issue":"3","key":"2819_CR53","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1517\/17425255.1.3.447","volume":"1","author":"M Strolin Benedetti","year":"2005","unstructured":"Strolin Benedetti M, Whomsley R, Baltes EL (2005) Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin Drug Metab Toxicol 1(3):447\u2013471","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"5\u20136","key":"2819_CR54","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00702-022-02485-6","volume":"129","author":"R Taurines","year":"2022","unstructured":"Taurines R, Fekete S, Preuss-Wiedenhoff A, Warnke A, Wewetzer C, Plener P, Burger R, Gerlach M, Romanos M, Egberts KM (2022) Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone. J Neural Transmission (Vienna Austria: 1996) 129(5\u20136):689\u2013701","journal-title":"J Neural Transmission (Vienna Austria: 1996)"},{"issue":"7","key":"2819_CR55","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1017\/S1461145712001320","volume":"17","author":"N Toteja","year":"2014","unstructured":"Toteja N, Gallego JA, Saito E, Gerhard T, Winterstein A, Olfson M, Correll CU (2014) Prevalence and correlates of antipsychotic polypharmacy in children and adolescents receiving antipsychotic treatment. Int J Neuropsychopharmacol 17(7):1095\u20131105","journal-title":"Int J Neuropsychopharmacol"},{"issue":"3","key":"2819_CR56","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2165\/00003088-199834030-00005","volume":"34","author":"S Ulrich","year":"1998","unstructured":"Ulrich S, Wurthmann C, Brosz M, Meyer FP (1998) The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia. Clin Pharmacokinet 34(3):227\u2013263","journal-title":"Clin Pharmacokinet"},{"issue":"3","key":"2819_CR57","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1024\/1422-4917\/a000632","volume":"47","author":"TD Vloet","year":"2019","unstructured":"Vloet TD, Egberts K, Taurines R, Wewetzer C, Mehler-Wex C, Plener PL, Romanos M, Gerlach M (2019) Polypharmazie in Der Anwendung Von Psychopharmaka in Der Deutschen Kinder- Und Jugendpsychiatrie \u2013 h\u00e4ufiger Regel als Ausnahme (polypharmacy of psychotropic drugs in child and adolescent psychiatry in Germany - rather the rule than the exception). Z fur Kinder- und Jugendpsychiatrie Und Psychother 47(3):193\u2013202","journal-title":"Z fur Kinder- und Jugendpsychiatrie Und Psychother"},{"issue":"1\u20133","key":"2819_CR58","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ejphar.2006.07.008","volume":"546","author":"MD Wood","year":"2006","unstructured":"Wood MD, Scott C, Clarke K, Westaway J, Davies CH, Reavill C, Hill M, Rourke C, Newson M, Jones DNC, Forbes IT, Gribble A (2006) Aripiprazole and its human metabolite are partial agonists at the human dopamine D2 receptor, but the rodent metabolite displays antagonist properties. Eur J Pharmacol 546(1\u20133):88\u201394","journal-title":"Eur J Pharmacol"}],"container-title":["Journal of Neural Transmission"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-024-02819-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00702-024-02819-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-024-02819-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T17:41:54Z","timestamp":1738345314000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00702-024-02819-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,2]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["2819"],"URL":"https:\/\/doi.org\/10.1007\/s00702-024-02819-6","relation":{},"ISSN":["0300-9564","1435-1463"],"issn-type":[{"value":"0300-9564","type":"print"},{"value":"1435-1463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,2]]},"assertion":[{"value":"21 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"KE, MR, RT and PP received grant research support from BfArM. MR currently receives a research grant from Kids-Safe, Innovation Committee of the German Federal Joint Committee (G-BA grant number 01NVF16021). PP receives grant research support from the German Federal Ministry of Education and Research (BMBF) and was involved in clinical trials from Servier and Lundbeck; he received an advisor honorarium from Boehringer Ingelheim and speaker\u2019s honoraria from Shire, Infectopharm and Gerot Lannach. CUC has been a consultant and\/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen\/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Sage, Supernus, Tolmar and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, PsiloSterics and Quantic. TB received personal fees from serving as an advisor or consultant to from eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche and Takeda; receiving conference attendance support, conference support, or speaking fees from or speaker\u2019s fee by Janssen, Medice and Takeda; and receiving royalties from Hogrefe, Kohlhammer, CIP-Medien, and Oxford University Press. S.W.has received in the last 5 years royalties from Thieme, Hogrefe, Kohlhammer, Springer, Beltz. In 2023 she will receive speakers honorary from Takeda and Medice. Her work was supported in the last years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann M\u00fcller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz, Heuberg Fonds, National Government of Health (BAG), Gesundheitsf\u00f6rderung Schweiz and Horizon Europe. Outside professional activities and interests are declared under the link of the University of Zurich  MKoe receives royalties from publishing companies as an author of books. He served as PI or CI in clinical trials of Lundbeck, Pascoe and Janssen-Cilag. He served as scientific advisor for Janssen. The present work is unrelated to the above grants and relationships. The other authors (JC, HC, KSM, RT, SF, CW, AK, KR, UM, PH, SU, MSC, HR, GA, WB, TH, MKae, CR, GS, MG, and CF) declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}