TY - JOUR
T1 - The future of child and adolescent clinical psychopharmacology
T2 - A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications
AU - Cortese, Samuele
AU - McGinn, Katherine
AU - Højlund, Mikkel
AU - Apter, Alan
AU - Arango, Celso
AU - Baeza, Immaculada
AU - Banaschewski, Tobias
AU - Buitelaar, Jan
AU - Castro-Fornieles, Josefina
AU - Coghill, David
AU - Cohen, David
AU - Grünblatt, Edna
AU - Hoekstra, Pieter J.
AU - James, Anthony
AU - Jeppesen, Pia
AU - Nagy, Péter
AU - Pagsberg, Anne Katrine
AU - Parellada, Mara
AU - Persico, Antonio M.
AU - Purper-Ouakil, Diane
AU - Roessner, Veit
AU - Santosh, Paramala
AU - Simonoff, Emily
AU - Stevanovic, Dejan
AU - Stringaris, Argyris
AU - Vitiello, Benedetto
AU - Walitza, Susanne
AU - Weizman, Abraham
AU - Wohlfarth, Tamar
AU - Wong, Ian C. K.
AU - Zalsman, Gil
AU - Zuddas, Alessandro
AU - Moreno, Carmen
AU - Solmi, Marco
AU - Correll, Christoph U.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023
Y1 - 2023
N2 - We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (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.
AB - We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (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.
KW - Adolescents
KW - Children
KW - Dietary interventions
KW - Medications
KW - Probiotics
KW - Psychopharmacology
U2 - 10.1016/j.neubiorev.2023.105149
DO - 10.1016/j.neubiorev.2023.105149
M3 - Review
C2 - 37001575
AN - SCOPUS:85153291444
VL - 149
JO - Neuroscience & Biobehavioral Reviews
JF - Neuroscience & Biobehavioral Reviews
SN - 0149-7634
M1 - 105149
ER -