The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung


  • Samuele Cortese - , University of Southampton, Solent NHS Trust, New York University, University of Nottingham (Autor:in)
  • Katherine McGinn - , University of Southampton, Wessex Deanery (Autor:in)
  • Mikkel Højlund - , Mental Health Services in the Region of Southern Denmark, University of Southern Denmark (Autor:in)
  • Alan Apter - , Schneider Childrens Medical Center Israel, Reichman University (Autor:in)
  • Celso Arango - , Complutense University (Autor:in)
  • Immaculada Baeza - , University of Barcelona (Autor:in)
  • Tobias Banaschewski - , Universität Heidelberg (Autor:in)
  • Jan Buitelaar - , Radboud University Nijmegen, Karakter Child and Adolescent Psychiatry University Centre (Autor:in)
  • Josefina Castro-Fornieles - , University of Barcelona (Autor:in)
  • David Coghill - , University of Melbourne, Murdoch Children's Research Institute (Autor:in)
  • David Cohen - , Sorbonne Université (Autor:in)
  • Edna Grünblatt - , University of Zurich (Autor:in)
  • Pieter J. Hoekstra - , University of Groningen (Autor:in)
  • Anthony James - , University of Oxford, Oxford Health NHS Foundation Trust (Autor:in)
  • Pia Jeppesen - , Universität Kopenhagen, Capital Region of Denmark (Autor:in)
  • Péter Nagy - , Bethesda Children's Hospital (Autor:in)
  • Anne Katrine Pagsberg - , Universität Kopenhagen (Autor:in)
  • Mara Parellada - , Complutense University (Autor:in)
  • Antonio M. Persico - , University of Modena and Reggio Emilia (Autor:in)
  • Diane Purper-Ouakil - , CHU Montpellier, Université de Versailles Saint-Quentin-en-Yvelines (Autor:in)
  • Veit Roessner - , Klinik und Poliklinik für Kinder- und Jugendpsychiatrie (Autor:in)
  • Paramala Santosh - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • Emily Simonoff - , South London and Maudsley NHS Foundation Trust (Autor:in)
  • Dejan Stevanovic - , Clinic for Neurology and Psychiatry for Children and Youth Belgrade, University of Gothenburg (Autor:in)
  • Argyris Stringaris - , University College London, National and Kapodistrian University of Athens (Autor:in)
  • Benedetto Vitiello - , University of Turin (Autor:in)
  • Susanne Walitza - , University of Zurich (Autor:in)
  • Abraham Weizman - , Geha Mental Health Center (Autor:in)
  • Tamar Wohlfarth - , University of Amsterdam (Autor:in)
  • Ian C.K. Wong - , The University of Hong Kong, University College London, Aston University (Autor:in)
  • Gil Zalsman - , Tel Aviv University, Columbia University (Autor:in)
  • Alessandro Zuddas - , Università degli Studi di Cagliari (Autor:in)
  • Carmen Moreno - , University of Southampton (Autor:in)
  • Marco Solmi - , University of Ottawa, King's College London (KCL), Charité – Universitätsmedizin Berlin (Autor:in)
  • Christoph U. Correll - , Charité – Universitätsmedizin Berlin, Zucker Hillside Hospital, Hofstra University (Autor:in)


We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched and (from 01/01/2010–08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.


FachzeitschriftNeuroscience and biobehavioral reviews
PublikationsstatusVeröffentlicht - Juni 2023

Externe IDs

PubMed 37001575


Ziele für nachhaltige Entwicklung


  • Adolescents, Children, Dietary interventions, Medications, Probiotics, Psychopharmacology, Humans, Randomized Controlled Trials as Topic, Adolescent, Attention Deficit Disorder with Hyperactivity/drug therapy, Child, Prader-Willi Syndrome, Clinical Trials, Phase II as Topic