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

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  • Samuele Cortese
  • Katherine McGinn
  • Mikkel Højlund
  • Alan Apter
  • Celso Arango
  • Immaculada Baeza
  • Tobias Banaschewski
  • Jan Buitelaar
  • Josefina Castro-Fornieles
  • David Coghill
  • David Cohen
  • Edna Grünblatt
  • Pieter J. Hoekstra
  • Anthony James
  • Péter Nagy
  • Mara Parellada
  • Antonio M. Persico
  • Diane Purper-Ouakil
  • Veit Roessner
  • Paramala Santosh
  • Emily Simonoff
  • Dejan Stevanovic
  • Argyris Stringaris
  • Benedetto Vitiello
  • Susanne Walitza
  • Abraham Weizman
  • Tamar Wohlfarth
  • Ian C. K. Wong
  • Gil Zalsman
  • Alessandro Zuddas
  • Carmen Moreno
  • Marco Solmi
  • Christoph U. Correll

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.

Original languageEnglish
Article number105149
JournalNeuroscience and Biobehavioral Reviews
Number of pages30
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

    Research areas

  • Adolescents, Children, Dietary interventions, Medications, Probiotics, Psychopharmacology

ID: 367259056