Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Christoph U Correll; Samuele Cortese; Giovanni Croatto; Francesco Monaco; Damir Krinitski; Gonzalo Arrondo; Edoardo G Ostinelli; Caroline Zangani; Michele Fornaro; Andrés Estradé; Paolo Fusar-Poli; Andre F Carvalho; Marco Solmi

doi:10.1002/wps.20881

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

World Psychiatry. 2021 Jun;20(2):244-275. doi: 10.1002/wps.20881.

Authors

Christoph U Correll^{1

2

3

4}, Samuele Cortese^{5

6

7

8

9}, Giovanni Croatto¹⁰, Francesco Monaco¹¹, Damir Krinitski¹², Gonzalo Arrondo^{5

13}, Edoardo G Ostinelli¹⁴, Caroline Zangani¹⁵, Michele Fornaro¹⁶, Andrés Estradé^{17

18}, Paolo Fusar-Poli^{17

19

20

21}, Andre F Carvalho^{22

23}, Marco Solmi^{10

17}

Affiliations

¹ Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, NY, USA.
² Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
³ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
⁴ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁵ Center for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
⁶ Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.
⁷ Solent NHS Trust, Southampton, UK.
⁸ Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA.
⁹ Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
¹⁰ Neurosciences Department, University of Padua, Padua, Italy.
¹¹ Department of Mental Health, ASL Salerno, Salerno, Italy.
¹² Integrated Psychiatry Winterthur, Winterthur, Switzerland.
¹³ Mind-Brain Group, Institute for Culture and Society, University of Navarra, Pamplona, Spain.
¹⁴ Psychiatry Department, Oxford University, Oxford, UK.
¹⁵ Department of Health Sciences, University of Milan, Milan, Italy.
¹⁶ Department of Psychiatry, Federico II University, Naples, Italy.
¹⁷ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
¹⁸ Department of Clinical and Health Psychology, Catholic University, Montevideo, Uruguay.
¹⁹ OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
²⁰ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
²¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
²² Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
²³ Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.

Abstract

Top-tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour-nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter-ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta-analyses (NMAs) and meta-analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co-primary outcomes were disease-specific symptom reduction and all-cause discontinuation ("acceptability"). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co-primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta-analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention-deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive-compulsive disorder; CBT in post-traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence-based information for clinical decision making.

Keywords: ADHD; Children; acceptability; adolescents; autism; brain stimulation; disruptive behavior disorders; efficacy; pharmacotherapy; psychosocial interventions; psychotherapies.