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 -