title: Acute Antipsychotic Treatment of Children and Adolescents With Schizophrenia-Spectrum Disorders: A Systematic Review and Network Meta-Analysis.
abstract: 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.
  
  
  METHODS
  The authors systematically searched MEDLINE, the Cochrane Library, and clinicaltrials.gov 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.
  
  
  CONCLUSIONS
  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; https://www.crd.york.ac.uk/PROSPERO/; CRD42013006676.
authors.affiliation: Child and Adolescent Mental Health Center, Mental Health Services, Capital Region of Denmark and the Faculty of Health Science, University of Copenhagen, Denmark. Electronic address: Anne.Katrine.Pagsberg@Regionh.dk.
authors.forename: Anne Katrine
authors.initials: AK
authors.lastname: Pagsberg
authors.affiliation: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Capital Region, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: Danish Council for the Use of Expensive Hospital Medicines Secretariat, Copenhagen.
authors.forename: Dorte
authors.initials: D
authors.lastname: Glintborg
authors.affiliation: University of Southern Denmark, Odense.
authors.forename: Anne Dorte
authors.initials: AD
authors.lastname: Stenstrøm
authors.affiliation: Psychiatric Centre Copenhagen, University Hospital Copenhagen and the Laboratory of Neuropsychiatry, University of Copenhagen.
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.affiliation: Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY.
authors.forename: Christoph Ulrich
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Capital Region, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotics; network meta-analysis; schizophrenia