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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 publication




Journal article


Neurosci Biobehav Rev

Publication Date





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