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Acute Antipsychotic Treatment Of Children And Adolescents With Schizophrenia-Spectrum Disorders: A Systematic Review And Network Meta-Analysis.

A. K. Pagsberg, S. Tarp, Dorte Glintborg, A. D. Stenstrøm, A. Fink-Jensen, C. Correll, R. Christensen
Published 2017 · Psychology, Medicine

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OBJECTIVE To determine the comparative efficacy and safety of antipsychotics for youth with early-onset schizophrenia using network meta-analytic methods combining direct and indirect trial data. METHOD The authors systematically searched MEDLINE, the Cochrane Library, and and selected randomized controlled trials allocating youth with schizophrenia spectrum disorders to a (non-clozapine) antipsychotic versus placebo or another antipsychotic. Major efficacy outcomes were Positive and Negative Syndrome Scale (PANSS) total and positive symptoms. Major safety outcomes were weight, plasma triglyceride levels, extrapyramidal symptoms, akathisia, and all-cause discontinuation. Sixteen additional outcomes were analyzed. A random-effects arm-based network meta-analysis was applied, and consistency was assessed by pairwise meta-analysis. Confidence in PANSS total estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS Twelve 6- to 12-week trials (N = 2,158; 8-19 years old; 61% boys) involving 8 antipsychotics (aripiprazole, asenapine, paliperidone, risperidone, quetiapine, olanzapine, molindone, and ziprasidone) were analyzed. PANSS total symptom change was comparable among antipsychotics (low- to moderate-quality evidence), except ziprasidone (very low- to low-quality evidence), and all antipsychotics were superior to placebo (low- to high-quality evidence), except ziprasidone and asenapine (low- to moderate-quality evidence). PANSS positive changes and additional efficacy outcomes were comparable among antipsychotics. Weight gain was primarily associated with olanzapine; extrapyramidal symptoms and akathisia were associated with molindone; and prolactin increased with risperidone, paliperidone, and olanzapine. Serious adverse events, discontinuation of treatment, sedation, insomnia, or change in triglycerides did not differ among antipsychotics. CONCLUSION This network meta-analysis showed comparable efficacy among antipsychotics for early-onset schizophrenia, except that efficacy appeared inferior for ziprasidone and unclear for asenapine. Adverse reaction profiles varied substantially among the investigated antipsychotics and were largely consistent with prior findings in adults. Protocol registration information-Antipsychotic Treatment for Children With Schizophrenia Spectrum Disorders: Network Meta-Analysis of Randomised Trials;; CRD42013006676.
This paper references
An open-label randomized comparison of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia.
T. Mozes (2006)
Adverse Effects of Second-Generation Antipsychotics in Children and Adolescents: A Bayesian Meta-Analysis
D. Cohen (2012)
Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes.
C. Correll (2008)
A depression rating scale for children.
E. Poznanski (1979)
A Systematic Review and Network Meta-Analysis to Assess the Relative Efficacy of Antipsychotics for the Treatment of Positive and Negative Symptoms in Early-Onset Schizophrenia
R. Harvey (2016)
Antipsychotic medication in adolescents suffering from schizophrenia: a meta-analysis of randomized controlled trials.
Ignazio Ardizzone (2010)
Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.
L. Sikich (2008)
Recognition and management of psychosis and schizophrenia in children and young people: summary of NICE guidance
T. Kendall (2013)
The combination of estimates from different experiments.
W. Cochran (1954)
Olanzapine, risperidone and haloperidol in the treatment of adolescent patients with schizophrenia
D. Gothelf (2003)
Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach
B. Schimmelmann (2013)
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia.
R. Findling (2008)
Olanzapine versus placebo in adolescents with schizophrenia: a 6-week, randomized, double-blind, placebo-controlled trial.
L. Kryzhanovskaya (2009)
A systematic review of the long-term outcome of early onset schizophrenia
L. Clemmensen (2012)
A trial of quetiapine compared with risperidone in the treatment of first onset psychosis among 15- to 18-year-old adolescents
H. Swadi (2010)
Meta-analysis in clinical trials.
R. Dersimonian (1986)
Diagnostic and Statistical Manual of Mental Disorders
J. Williams (2013)
The Brief Psychiatric Rating Scale
J. Overall (1962)
The Child and Adolescent Functional Assessment Scale (CAFAS): Review and Current Status
M. Bates (2001)
The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations
B. Hutton (2015)
The positive and negative syndrome scale (PANSS) for schizophrenia.
S. R. Kay (1987)
Antipsychotic medication for childhood-onset schizophrenia.
E. Kennedy (2007)
Mixed treatment comparison meta-analysis of complex interventions: psychological interventions in coronary heart disease.
N. Welton (2009)
The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration
A. Liberati (2009)
Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics.
C. Correll (2011)
Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders: protocol for a network meta-analysis of randomised trials
A. K. Pagsberg (2014)
Measuring inconsistency in meta-analyses
J. Higgins (2003)
Schizophrenia and related disorders in children and adolescents.
H. Remschmidt (2005)
Systematic review of the efficacy and tolerability of clozapine in the treatment of youth with early onset schizophrenia.
C. Schneider (2014)
Evaluation of networks of randomized trials
G. Salanti (2008)
Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
S. Leucht (2013)
Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: a critical literature review
M. De Hert (2016)
Safety and Efficacy from an 8 Week Double-Blind Trial and a 26 Week Open-Label Extension of Asenapine in Adolescents with Schizophrenia.
R. Findling (2015)
Evidence base for using atypical antipsychotics for psychosis in adolescents.
S. S. Datta (2014)
GRADE guidelines: 5. Rating the quality of evidence--publication bias.
G. Guyatt (2011)
Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review
M. De Hert (2016)
Second-generation and newly approved antipsychotics, serum prolactin levels and sexual dysfunctions: a critical literature review
M. De Hert (2014)
A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview
J. Singh (2009)
Corrected QT changes during antipsychotic treatment of children and adolescents: a systematic review and meta-analysis of clinical trials.
K. G. Jensen (2015)
A Randomized, Double-Blind Study of Paliperidone Extended-Release in Treatment of Acute Schizophrenia in Adolescents
J. Singh (2011)
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
J. P. Higgins (2011)
Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled efficacy and long-term open-extension study.
R. Findling (2013)
Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study.
Adam J. Savitz (2015)
A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia.
M. Haas (2009)
Changes in the diagnosed incidence of early onset schizophrenia over four decades
N. Okkels (2013)
A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis
M. Puhan (2014)
Efficacy and safety of quetiapine in adolescents with schizophrenia investigated in a 6-week, double-blind, placebo-controlled trial.
R. Findling (2012)
The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.
H. Bucher (1997)
Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder
J. Rapoport (2011)
Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study.
M. Haas (2009)
Some remarks on etiological aspects of early-onset schizophrenia
C. Eggers (2009)
A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders.
J. B. Jensen (2008)
GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology.
G. Guyatt (2011)
Antipsychotics in early onset Schizophrenia
J. Armenteros (2005)
A children's global assessment scale (CGAS).
D. Shaffer (1983)
Combination of direct and indirect evidence in mixed treatment comparisons.
G. Lu (2004)

This paper is referenced by
Dilemmas in the treatment of early-onset first-episode psychosis
Daniel Hayes (2018)
Pharmacological interventions in clozapine-refractory schizophrenia
S.R.T. Veerman (2017)
Twenty years of progress in paediatric psychopharmacology: accomplishments and unmet needs
B. Vitiello (2018)
Association of dopamine D2 receptor gene polymorphisms with prolactin levels related to risperidone treatment: A systematic review and meta‐analysis
Lingyue Ma (2019)
The evidence-based choice for antipsychotics in children and adolescents should be guaranteed
D. Putignano (2019)
Meta-Review: Network Meta-Analyses in Child and Adolescent Psychiatry.
S. Cortese (2019)
Addressing mental health needs: an integral part of COVID‐19 response
Tedros Adhanom Ghebreyesus (2020)
Efficacy, acceptability, and tolerability of antipsychotics in children and adolescents with schizophrenia: A network meta-analysis
M. Krause (2018)
[Evidence-based treatment of acute psychotic episode and schizophrenia in children and adolescents].
D V Ivashchenko (2019)
Clinical Practice Guidelines for the Management of Schizophrenia in Children and Adolescents
S. Grover (2019)
Psychosis in Children and Adolescents.
J. McClellan (2018)
Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness
Victor Mazereel (2020)
Dosing and Monitoring: Children and Adolescents.
G. Hirsch (2018)
Psychopharmacologic Treatment of Schizophrenia in Adolescents and Children.
Esther S Lee (2020)
2 Methodological Considerations 2 . 1 Search Strategy and Selection Criteria
S. R. T. Veerman (2017)
Editorial: Making Use of What We Know: Medical Decision-Making and Antipsychotics.
Gail A. Edelsohn (2019)
Antipsychotics in adolescent-onset psychosis: a work in progress.
A. C. James (2017)
A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression
G. Masi (2017)
Childhood-Onset Schizophrenia and Early-onset Schizophrenia Spectrum Disorders: An Update.
David I Driver (2020)
Cardiometabolic Adverse Effects and Its Predictors in Children and Adolescents With First-Episode Psychosis During Treatment With Quetiapine-Extended Release Versus Aripiprazole: 12-Week Results From the Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis (TEA) Trial.
K. G. Jensen (2019)
Management of schizophrenia and bipolar disorder in pediatricpractice
I. Martsenkovsky (2019)
Effective Medications for Treating Psychosis in School-Aged Youth
Zachary B. Millman (2019)
Use of Antipsychotic Drugs for Psychotic Disorders in Children
Shahana Ayub (2018)
Psychosocial interventions versus antipsychotics forearly-onset psychosis: can we fill the evidence gap?
S. Jauhar (2020)
Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: the multicentre, double-blind, randomised tolerability and efficacy of antipsychotics (TEA) trial.
A. K. Pagsberg (2017)
The development of monoaminergic neurotransmitter systems in childhood and adolescence
M. Pitzer (2019)
Efficacy of Olanzapine for High and Moderate Emetogenic Chemotherapy in Children
So Rae Lee (2020)
Pharmacogenetics of antipsychotics in adolescents with acute psychotic episode during first 14 days after admission: effectiveness and safety evaluation.
D. Ivashchenko (2020)
Behandlung unter besonderen Bedingungen (Modul 4c)
W. Gaebel (2019)
The impact of quetiapine on the brain lipidome in a cuprizone-induced mouse model of schizophrenia.
C. Zhou (2020)
Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.
Rebecca Rodrigues (2020)
Promoting a patient-centered, transdiagnostic approach to prevention of severe mental illness
M. K. Rimvall (2020)
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