Efficacy, acceptability, and tolerability of antipsychotics in children and adolescents with schizophrenia: A network meta-analysis

Eur Neuropsychopharmacol. 2018 Jun;28(6):659-674. doi: 10.1016/j.euroneuro.2018.03.008. Epub 2018 May 24.


Children and adolescents with schizophrenia are a particularly vulnerable group. Thus, we integrated all the randomized evidence from the available antipsychotics used for this subgroup by performing a network-meta-analysis and pairwise meta-analysis using a random-effects model. We searched multiple databases up to Nov 17, 2016 (final update search in PubMed: Dec 12, 2017). The primary outcome was efficacy as measured by overall change/endpoint in symptoms of schizophrenia. Secondary outcomes included positive and negative symptoms, response, dropouts, quality of life, social functioning, weight gain, sedation, prolactin, extrapyramidal side effects (EPS) and antiparkinsonian medication. Twenty-eight randomized controlled trials (RCTs) with 3003 unique participants (58% males; mean age 14.41 years) published from 1967 to 2017 were identified. Clozapine was significantly more effective than all other analyzed antipsychotics. Nearly all antipsychotics were more efficacious compared to placebo, but ziprasidone showed no efficacy. In terms of preventing weight gain, molindone, lurasidone and ziprasidone were benign. The highest weight gain was found for clozapine, quetiapine and olanzapine. Most antipsychotics had some sedating effects. Risperidone, haloperidol, paliperidone and olanzapine were associated with prolactin increase. There were evidence gaps for some drugs and many outcomes, especially safety outcomes. Most of the comparisons are based only on one study or just on indirect evidence. Nevertheless, the available direct and indirect evidence showed that the treatment effects were similar compared to findings in adult patients with schizophrenia.

Keywords: Antipsychotics; Children; Efficacy; Meta-analysis; Schizophrenia; Systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Antipsychotic Agents / therapeutic use*
  • Child
  • Female
  • Humans
  • Male
  • Network Meta-Analysis*
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Treatment Outcome*


  • Antipsychotic Agents