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
Samuele Cortese
(1, 2, 3, 4)
,
Katherine Mcginn
(4, 1)
,
Mikkel Højlund
(5, 4)
,
Alan S. Apter
(4, 6)
,
Celso Arango
(4, 7)
,
Immaculada Baeza
(8, 4)
,
Tobias J. Banaschewski
(4, 9)
,
Jan K. Buitelaar
(4, 10)
,
Josefina Castro-Fornieles
(8, 4)
,
David R. Coghill
(4, 11)
,
David Cohen
(12, 13, 4)
,
Edna Grünblatt
(4, 14)
,
Pieter J. Hoekstra
(4, 15)
,
Anthony C. James
(4, 16)
,
Pia Jeppesen
(17, 4)
,
Péter Nagy
(4)
,
Anne Katrine Pagsberg
(17, 4)
,
Mara José Parellada
(4, 7)
,
Antonio Maria Persico
(4, 18)
,
Diane O. Purper-Ouakil
(19, 20, 4)
,
Veit Roessner
(4, 21)
,
Paramala Janardhanan Santosh
(4, 22)
,
Emily A. Simonoff
(4, 22)
,
Dejan Stevanovic
(23, 4)
,
Argyrios K. Stringaris
(24, 25, 4)
,
Benedetto Vitiello
(4, 26)
,
Susanne Walitza
(4, 14)
,
A. Weizman
(4)
,
Tamar D. Wohlfarth
(4, 27)
,
Ian C.K. Wong
(28, 4, 24)
,
Gil Zalsman
(29, 30, 4)
,
Alessandro Zuddas
(31, 4)
,
Carmen Moreno
(4, 1)
,
Marco Solmi
(32, 22, 33, 4)
,
Christophe U. Correll
(33, 34, 4)
1
University of Southampton
2 NYU Langone Health [New York]
3 UON - University of Nottingham, UK
4 The Feinstein Institute for Medical Research
5 SDU - University of Southern Denmark
6 RUNI - Reichman University [Herzliya]
7 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
8 University of Barcelona
9 Universität Heidelberg [Heidelberg] = Heidelberg University
10 Radboud University Medical Center [Nijmegen]
11 University of Melbourne
12 CHU Pitié-Salpêtrière [AP-HP]
13 ISIR - Institut des Systèmes Intelligents et de Robotique
14 UZH - Universität Zürich [Zürich] = University of Zurich
15 University of Groningen [Groningen]
16 University of Oxford
17 UCPH - University of Copenhagen = Københavns Universitet
18 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
19 CESP - Centre de recherche en épidémiologie et santé des populations
20 CHU Montpellier
21 TU Dresden - Technische Universität Dresden = Dresden University of Technology
22 King‘s College London
23 GU - Göteborgs Universitet = University of Gothenburg
24 UCL - University College of London [London]
25 NKUA - National and Kapodistrian University of Athens
26 UNITO - Università degli studi di Torino = University of Turin
27 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
28 HKU - The University of Hong Kong
29 TAU - Tel Aviv University
30 Columbia University [New York]
31 University of Cagliari
32 University of Ottawa [Ottawa]
33 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
34 ZHH - Zucker Hillside Hospital [Glen Oaks, NY, USA]
2 NYU Langone Health [New York]
3 UON - University of Nottingham, UK
4 The Feinstein Institute for Medical Research
5 SDU - University of Southern Denmark
6 RUNI - Reichman University [Herzliya]
7 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
8 University of Barcelona
9 Universität Heidelberg [Heidelberg] = Heidelberg University
10 Radboud University Medical Center [Nijmegen]
11 University of Melbourne
12 CHU Pitié-Salpêtrière [AP-HP]
13 ISIR - Institut des Systèmes Intelligents et de Robotique
14 UZH - Universität Zürich [Zürich] = University of Zurich
15 University of Groningen [Groningen]
16 University of Oxford
17 UCPH - University of Copenhagen = Københavns Universitet
18 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
19 CESP - Centre de recherche en épidémiologie et santé des populations
20 CHU Montpellier
21 TU Dresden - Technische Universität Dresden = Dresden University of Technology
22 King‘s College London
23 GU - Göteborgs Universitet = University of Gothenburg
24 UCL - University College of London [London]
25 NKUA - National and Kapodistrian University of Athens
26 UNITO - Università degli studi di Torino = University of Turin
27 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
28 HKU - The University of Hong Kong
29 TAU - Tel Aviv University
30 Columbia University [New York]
31 University of Cagliari
32 University of Ottawa [Ottawa]
33 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
34 ZHH - Zucker Hillside Hospital [Glen Oaks, NY, USA]
Samuele Cortese
- Fonction : Auteur correspondant
- PersonId : 1167294
- ORCID : 0000-0001-5877-8075
Mikkel Højlund
- Fonction : Auteur
- PersonId : 1256799
- ORCID : 0000-0002-5786-5203
David R. Coghill
- Fonction : Auteur
- PersonId : 1192011
- ORCID : 0000-0003-3017-9737
Edna Grünblatt
- Fonction : Auteur
- PersonId : 1256800
- ORCID : 0000-0001-8505-7265
Anthony C. James
- Fonction : Auteur
Anne Katrine Pagsberg
- Fonction : Auteur
- PersonId : 1256801
- ORCID : 0000-0003-0818-8338
Mara José Parellada
- Fonction : Auteur
- PersonId : 1256802
- ORCID : 0000-0001-7977-3601
Veit Roessner
- Fonction : Auteur
- PersonId : 1256803
- ORCID : 0000-0002-1873-7081
Paramala Janardhanan Santosh
- Fonction : Auteur
- PersonId : 763393
- ORCID : 0000-0003-4830-5893
Susanne Walitza
- Fonction : Auteur
- PersonId : 1256804
- ORCID : 0000-0002-8161-8683
A. Weizman
- Fonction : Auteur
- PersonId : 1256805
- ORCID : 0000-0002-9765-8938
Carmen Moreno
- Fonction : Auteur
- PersonId : 1256806
- ORCID : 0000-0003-0541-4846
Marco Solmi
- Fonction : Auteur
- PersonId : 804144
- ORCID : 0000-0003-4877-7233
Résumé
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.
Origine : Accord explicite pour ce dépôt
Licence : CC BY - Paternité
Licence : CC BY - Paternité